CBDA vs CBD Absorption: CBDA Reaches Far Higher Blood Levels

Showing 60 of 1985 Cmax/Tmax/AUC values (human first). All 2028 values are in /api/supplements/cbd.

1. Human Stott CG, White L, Wright S, Wilbraham D, Guy GW. A phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray. European journal of clinical pharmacology. 2013;69(4):825-34. PMID 23052407. doi:10.1007/s00228-012-1393-4 PubMed · DOI · open-label, single-dose, randomized fed–fasted two-period crossover, n=12

Showing 60 of 82 Cmax/Tmax/AUC values (human first). All 82 values are in /api/supplements/cbda.

1. Human Elder HJ, Zamarripa CA, Klausner M, Wakshlag J, Davis R, Dresser B, Kjaer C, Weerts EM, Vandrey R, Spindle TR. The Pharmacokinetics and Pharmacodynamics of a Hemp-Derived "Full-Spectrum" Oral Cannabinoid Product with a 1:1 Ratio of Cannabidiol to Cannabidiolic Acid and Delta-9-Tetrahydrocannabinol to Delta-9-Tetrahydrocannabinolic Acid: A Double-Blind, Placebo-Controlled, Within-Subjects Human Laboratory Study. Cannabis and cannabinoid research. 2025;10(2):e299-e313. PMID 40040421. doi:10.1089/can.2024.0187 PubMed · DOI · other (double-blind, placebo-controlled, within-subjects, ascending-dose; placebo randomly within sequence), n=15 (PD); 12 (PK)
2. Rodent Anderson LL, Low IK, Banister SD, McGregor IS, Arnold JC. Pharmacokinetics of Phytocannabinoid Acids and Anticonvulsant Effect of Cannabidiolic Acid in a Mouse Model of Dravet Syndrome. Journal of natural products. 2019;82(11):3047-3055. PMID 31686510. doi:10.1021/acs.jnatprod.9b00600 PubMed · DOI · other (single-dose intraperitoneal PK in mice, terminal sampling per time point)
3. Other animal Rooney TA, Carpenter JW, KuKanich B, Gardhouse SM, Magnin GC, Tully TN. Feeding decreases the oral bioavailability of cannabidiol and cannabidiolic acid in hemp oil in New Zealand White rabbits (Oryctolagus cuniculus). American journal of veterinary research. 2022;83(10). PMID 35947680. doi:10.2460/ajvr.22.01.0006 PubMed · DOI · other (two sequential single-dose phases in the same animals, fixed order, 2-week washout), n=6

matched single-form evidence only; non-overlapping ranges in 2 matched set(s), up to 1 studies per form (baseline correction not reported: capped at C). No head-to-head grade; indirect only.

matched single-form evidence only; non-overlapping ranges in 1 matched set(s), up to 1 studies per form (baseline correction not reported: capped at C). No head-to-head grade; indirect only.

no clear separation under matched conditions; not graded. No head-to-head grade; indirect only.

1. HumanComparative Pharmacokinetics and Safety of Cannabidiol in a Powder Formulation, CBtru®, vs an Oil-Based Formulation, Epidyolex®, Under Fasted and Fed Conditions in Healthy Participants: A Randomized Open-Label Cross-Over Phase I Study.
   CNS Drugs, 2026 · Design: randomized; crossover · abstract only (PubMed) · open access (hybrid)
   PMID 41888503DOI 10.1007/s40263-026-01280-1PMC13095987 (free full text)
   Verification: abstract-only auto-extract; unverified
   • Key findings · abstract:RESULTS: Under fasted conditions, CBtru® trended to higher CBD exposure (AUC0-24) and maximum concentration in plasma (Cmax) relative to Epidyolex®.
   • Key findings · abstract:Median tmax was shorter with CBtru® (3 h vs 3.5 h), indicating faster absorption.
   • Cmax · abstract:RESULTS: Under fasted conditions, CBtru® trended to higher CBD exposure (AUC0-24) and maximum concentration in plasma (Cmax) relative to Epidyolex®.
   • Tmax · abstract:Median tmax was shorter with CBtru® (3 h vs 3.5 h), indicating faster absorption.
   • Tmax · abstract:Under fed conditions, median tmax was shorter with CBtru® (5 h vs 8 h), while CBD and metabolite exposure were comparable.
   • AUC · abstract:RESULTS: Under fasted conditions, CBtru® trended to higher CBD exposure (AUC0-24) and maximum concentration in plasma (Cmax) relative to Epidyolex®.
   • Food effect · abstract:All participants received a single 400-mg dose of CBtru® and Epidyolex® under both fasted and fed conditions, with a minimum 14-day washout between administrations.
   • Food effect · abstract:RESULTS: Under fasted conditions, CBtru® trended to higher CBD exposure (AUC0-24) and maximum concentration in plasma (Cmax) relative to Epidyolex®.
   • Food effect · abstract:Under fed conditions, median tmax was shorter with CBtru® (5 h vs 8 h), while CBD and metabolite exposure were comparable.
2. HumanA Randomized, Single-Dose, Single-Sequence, Two-Arm (Fasting and Fed), Open-Label Study on the Oral Pharmacokinetics of a Nanodispersible Cannabidiol Solution (150 mg/mL).
   Med Cannabis Cannabinoids, 2026 · Design: randomized · n: 18 subjects · abstract only (PubMed) · open access (gold)
   PMID 41613360DOI 10.1159/000550104PMC12851612 (free full text)
   Verification: abstract-only auto-extract; unverified
   • Key findings · abstract:Plasma concentrations of CBD and its major metabolites, specifically 7-hydroxy-cannabidiol (7-OH-CBD) and 7-carboxy-cannabidiol (7-COOH-CBD) were quantified and the PK parameters including Cmax, time to reach maximum concentration (Tmax), AUC0-∞, and t½ were analyzed using non-compartmental modeling methods.
   • Key findings · abstract:RESULTS: The fed state significantly increased the area under the curve (AUC0-∞) for CBD by 3.0-fold (p < 0.0001) and prolonged the Tmax.
   • Key findings · abstract:Cmax was moderately higher in the fed state (1.3-fold).
   • Key findings · abstract:The 7-COOH-CBD metabolite reached the highest plasma concentration, followed by the parent[excerpt truncated in our database — see source]
   • Cmax · abstract:Plasma concentrations of CBD and its major metabolites, specifically 7-hydroxy-cannabidiol (7-OH-CBD) and 7-carboxy-cannabidiol (7-COOH-CBD) were quantified and the PK parameters including Cmax, time to reach maximum concentration (Tmax), AUC0-∞, and t½ were analyzed using non-compartmental modeling methods.
   • Cmax · abstract:Cmax was moderately higher in the fed state (1.3-fold).
   • Tmax · abstract:Plasma concentrations of CBD and its major metabolites, specifically 7-hydroxy-cannabidiol (7-OH-CBD) and 7-carboxy-cannabidiol (7-COOH-CBD) were quantified and the PK parameters including Cmax, time to reach maximum concentration (Tmax), AUC0-∞, and t½ were analyzed using non-compartmental modeling methods.
   • Tmax · abstract:RESULTS: The fed state significantly increased the area under the curve (AUC0-∞) for CBD by 3.0-fold (p < 0.0001) and prolonged the Tmax.
   • AUC · abstract:Plasma concentrations of CBD and its major metabolites, specifically 7-hydroxy-cannabidiol (7-OH-CBD) and 7-carboxy-cannabidiol (7-COOH-CBD) were quantified and the PK parameters including Cmax, time to reach maximum concentration (Tmax), AUC0-∞, and t½ were analyzed using non-compartmental modeling methods.
   • AUC · abstract:RESULTS: The fed state significantly increased the area under the curve (AUC0-∞) for CBD by 3.0-fold (p < 0.0001) and prolonged the Tmax.
   • Relative bioavailability · abstract:RESULTS: The fed state significantly increased the area under the curve (AUC0-∞) for CBD by 3.0-fold (p < 0.0001) and prolonged the Tmax.
   • Relative bioavailability · abstract:Cmax was moderately higher in the fed state (1.3-fold).
   • Food effect · abstract:The present study aimed to evaluate the PK profile of a novel nanodispersible CBD oral solution (150 mg/mL) under fasting and fed conditions in healthy male subjects.
   • Food effect · abstract:METHODS: In this randomized, single-dose, two-arm (fasting and fed), open-label trial, 18 subjects (9 fasting and 9 fed) received 300 mg of CBD (2 mL of 150 mg/mL).
   • Food effect · abstract:RESULTS: The fed state significantly increased the area under the curve (AUC0-∞) for CBD by 3.0-fold (p < 0.0001) and prolonged the Tmax.
   • Food effect · abstract:Cmax was moderately higher in the fed state (1.3-fold).
3. HumanEffect of Piperine Codelivery on the Oral Bioavailability of Cannabidiol: Insights from In Vitro Digestion and In Vivo Pharmacokinetics.
   J Agric Food Chem, 2026 · Design: not stated · full text (Europe PMC XML) + abstract · open access (hybrid)
   PMID 42311044DOI 10.1021/acs.jafc.6c02678PMC13329993 (free full text)
   Verification: full-text auto-extracted verbatim snippets with location; needs human check
   • AUC · full text, Section ' In Vivo Pharmacokinetics':The AUC0–6h presented the same trend observed for C max, with the lowest values obtained for NLC-CBDiso in both male and female mice.
   • AUC · full text, 1:Pharmacokinetic Parameters Obtained Following Single-Dose Oral Administration of CBDiso, NLC-CBDiso, and NLC-PIP-CBDiso to Male and Female Mice, Corresponding to 1 mg CBD   CBDiso NLC-CBDiso NLC-PIP-CBDiso   male female male female male female AUC0–6h (h ng/mL) 94.7 92.5 55.7 31.2 200.6 218.5 t max (h) 2.0 2.0 3.0 6.0 0.5 6 C max (ng/mL) 31.8 ± 19.4a,AB 44.2 ± 20.3a,A 15.6 ± 2.0a,B 11.9 ±
   • Food effect · full text, Section ' In Vivo Pharmacokinetics':The absolute oral bioavailability of free CBD is approximately 6–13%, mainly ascribed to poor water solubility and extended first-pass metabolism, where CBD undergoes monohydroxylation at C-7, forming the 7-OH metabolite, mediated by CYP450 enzymes, specifically CYP3A4 and CYP2C19. ,, However, it has been reported that the coingestion of CBD with lipid species can significantly enhance its bioava
   • Form comparison · full text, Section 'Stability, Bioaccessibility, and Estimat':The NLCs incorporated with both CBD and PIP presented increased stability for both NLC-PIP-CBDiso (98 ± 4%) and NLC-PIP-CBDext (103 ± 5%) compared to the NLC-CBDiso (73 ± 2%) and NLC-CBDext (83 ± 2%).
   • Form comparison · full text, Section ' In Vivo Pharmacokinetics':The absolute oral bioavailability of free CBD is approximately 6–13%, mainly ascribed to poor water solubility and extended first-pass metabolism, where CBD undergoes monohydroxylation at C-7, forming the 7-OH metabolite, mediated by CYP450 enzymes, specifically CYP3A4 and CYP2C19. ,, However, it has been reported that the coingestion of CBD with lipid species can significantly enhance its bioava
4. HumanSex-specific association between low oral doses of cannabidiol (CBD) and plasma concentration of anandamide (AEA), N-palmitoylethanolamine (PEA) and N-oleoylethanolamine (OEA) in healthy occasional cannabis users.
   J Cannabis Res, 2026 · Design: randomized; crossover · n: 70 healthy volunteers · full text (Europe PMC XML) + abstract · open access (gold)
   PMID 41514385DOI 10.1186/s42238-025-00356-xPMC12879445 (free full text)
   Verification: full-text auto-extracted verbatim snippets with location; needs human check
   • Key findings · abstract:Plasma AEA, PEA, and OEA were quantified by LC–MS, and dose–response assessed with linear mixed-effects models on plasma concentrations (model 1) and Area Under the Curve to increase (AUCi, model 2), including participant ID (nested in sequence) as random effect, and visit, sequence, sex, and baseline levels as fixed effects.
   • Key findings · abstract:RESULTS: Model 2 revealed a significant effect of CBD dose on AUCi of PEA and OEA, but not AEA.
   • Key findings · abstract:Pairwise comparisons showed that placebo was associated with significantly higher AUCi values than the 50 mg dose (p < 0.05; moderate effect sizes), and trended higher than[excerpt truncated in our database — see source]
   • AUC · abstract:Plasma AEA, PEA, and OEA were quantified by LC–MS, and dose–response assessed with linear mixed-effects models on plasma concentrations (model 1) and Area Under the Curve to increase (AUCi, model 2), including participant ID (nested in sequence) as random effect, and visit, sequence, sex, and baseline levels as fixed effects.
   • AUC · abstract:RESULTS: Model 2 revealed a significant effect of CBD dose on AUCi of PEA and OEA, but not AEA.
   • AUC · abstract:Pairwise comparisons showed that placebo was associated with significantly higher AUCi values than the 50 mg dose (p < 0.05; moderate effect sizes), and trended higher than
   • AUC · full text, Table 4:Pairwise comparison results for AEA, PEA and OEA AUCi estimated marginal means – transformed data from Model 2 Contrast Cohen’s d SE lower.CL upper.CL p-value AEA  (0 mg—20 mg) 0.046 0.170 −0.289 0.382 0.999  (0 mg—50 mg) 0.092 0.172 −0.247 0.431 0.984  (0 mg—100 mg) 0.000 0.171 −0.337 0.337 1.000  (0
   • AUC · full text, Table 5:Pairwise comparison results for AEA, PEA and OEA AUCi estimated marginal means within female subjects – transformed data from Model 2 Contrast Cohen’s d SE lower.CL upper.CL p-value AEA  (0 mg—20 mg) −0.138 0.232 −0.596 0.320 0.976  (0 mg—50 mg) 0.020 0.236 −0.445 0.486 1.000  (0 mg—100 mg) 0.011 0.23
   • AUC · full text, Section 'Association between AUCi and CBD doses':Further analysis of pairwise comparisons (shown in Table 4 below) revealed that, for both PEA and OEA, the placebo dose exhibited significantly higher AUCi values compared to the 50 mg CBD dose (p < 0.05), with a moderate effect size (PEA, Cohen’s d = 0.515, 95% CI [0.174; 0.857];
   • Form comparison · full text, Section 'Association between AUCi and CBD doses':Further analysis of pairwise comparisons (shown in Table 4 below) revealed that, for both PEA and OEA, the placebo dose exhibited significantly higher AUCi values compared to the 50 mg CBD dose (p < 0.05), with a moderate effect size (PEA, Cohen’s d = 0.515, 95% CI [0.174; 0.857];
   • Form comparison · full text, Section 'Association between AUCi and CBD doses':Additionally, for both PEA and OEA, the placebo dose trended towards higher AUCi values compared to the 200 mg CBD dose (p < 0.100), with a small-to-moderate effect size (PEA, Cohen’s d = 0.432, 95% CI [0.092; 0.772];
   • Form comparison · full text, Section 'Association between AUCi and CBD doses':Further analysis of pairwise comparisons within female subjects (shown in Table 5 below) revealed that, for both PEA and OEA, the placebo dose exhibited significantly higher AUCi values compared to the 200 mg CBD dose (p < 0.05), with a moderate-to-high effect size (PEA, Cohen’s d = 0.677, 95% CI [0.205;1.149];
5. HumanThe acute and chronic pharmacokinetics and pharmacodynamics of oral cannabidiol with and without low doses of delta-9-tetrahydrocannabinol.
   J Anal Toxicol, 2026 · Design: not stated · n: n = 60 · full text (Europe PMC XML) + abstract · open access (hybrid)
   PMID 40704705DOI 10.1093/jat/bkaf075PMC13079097 (free full text)
   Verification: full-text auto-extracted verbatim snippets with location; needs human check
   • Key findings · abstract:At least one participant receiving Δ9-THC doses of 1.0 mg or greater had at least 1 positive urine drug test (Δ9-THC-COOH immunoassay screen ≥50 ng/mL and LC-MS/MS confirmation ≥15 ng/mL) during Phase 1 and the number of positive urine samples increased with Δ9-THC dose.
   • Cmax · full text, Table 2.:100 mg CBD + 0 mg Δ9-THC (N = 10) 0.5 mg Δ9-THC (N = 10) 1.0 mg Δ9-THC (N = 10) 2.0 mg Δ9-THC (N = 10) 2.8 mg Δ9-THC (N = 10) 3.7mg Δ9-THC (N = 10) Cmax T  peak (hour) C  max T  max (hour) C  max T  max (hour) C  max T  max (hour) C  max T  max (hour) C  max T  max (hour) Subjective measures DEQ Drug effect 17.6 (20.5) 0.9 (0.4) 11.3 (21.3) 1.8 (1.6) 15.5 (24.8) 1.5 (1.3)
   • Cmax · full text, Section 'Phase 1':Formulations containing Δ9-THC produced dose-dependent increases in Δ9-THC, 11-OH-Δ9-THC, and Δ9-THC-COOH concentrations (Table S2). 11-OH-Δ9-THC and Δ9-THC-COOH showed dose-dependent increases in Cmax and AUC as indicated by a main effect of Drug Condition. 2.0, 2.8, and 3.7 mg Δ9-THC dose conditions had significantly higher Cmax and AUC values of 11-OH-Δ9-THC than CBD alone. 2.8 and 3.7 mg Δ9-TH
   • Cmax · full text, Section 'Phase 2':Day/Cmax accumulation ratio values revealed a significant increase in Δ9-THC-COOH concentrations by Day 14 in the 1.0 mg Δ9-THC condition, with trends toward significance observed across all Drug Conditions containing Δ9-THC for this metabolite.
   • Tmax · full text, Section 'Phase 1':Given the limited number of participants with detectable concentrations of Δ9-THC in the CBD alone, 0.5, and 1.0 mg Δ9-THC conditions, comparisons between Cmax, Tmax, and AUC values could not be conducted.
   • AUC · full text, Section 'Phase 1':Formulations containing Δ9-THC produced dose-dependent increases in Δ9-THC, 11-OH-Δ9-THC, and Δ9-THC-COOH concentrations (Table S2). 11-OH-Δ9-THC and Δ9-THC-COOH showed dose-dependent increases in Cmax and AUC as indicated by a main effect of Drug Condition. 2.0, 2.8, and 3.7 mg Δ9-THC dose conditions had significantly higher Cmax and AUC values of 11-OH-Δ9-THC than CBD alone. 2.8 and 3.7 mg Δ9-TH
   • AUC · full text, Section 'Phase 1':Given the limited number of participants with detectable concentrations of Δ9-THC in the CBD alone, 0.5, and 1.0 mg Δ9-THC conditions, comparisons between Cmax, Tmax, and AUC values could not be conducted.
   • AUC · full text, Section 'Phase 1':For 11-OH-Δ9-THC, ANOVAs showed a main effect of Drug Condition for Cmax and AUC, with 3.7 mg producing higher values than 1.0 mg Δ9-THC condition;
   • Form comparison · full text, Section 'Phase 2':Comparisons of the Day/Cmax accumulation ratio values revealed a significant increase in 7-COOH-CBD concentrations on Days 2, 7, and 14 for CBD alone and 3.7 mg Δ9-THC, with trends toward significance observed across all Drug Conditions for this metabolite, suggesting accumulation compared to Phase 1 (Table S3).
   • Form comparison · full text, Section 'Phase 2':Comparisons of the Day/Cmax accumulation ratio values revealed a significant increase in Δ9-THC-COOH concentrations on Day 14 for 1.0 mg Δ9-THC, with trends toward significance observed across all Drug Conditions containing Δ9-THC for this metabolite, suggesting accumulation compared to Phase 1 (Table S3).
6. HumanGenotype-Specific Safety and Pharmacokinetics of Cannabidiol in Healthy Volunteers.
   Clin Transl Sci, 2026 · Design: not stated · n: 33 healthy subjects · full text (Europe PMC XML) + abstract · open access (gold)
   PMID 41451876DOI 10.1111/cts.70455PMC12741916 (free full text)
   Verification: full-text auto-extracted verbatim snippets with location; needs human check
   • Key findings · abstract:Patients first received a single dose of cannabidiol 5 mg/kg orally with serial plasma concentrations measured.
   • Key findings · abstract:Later, patients were titrated to 5 mg/kg twice daily for 14 days to reach steady state with serial plasma concentrations measured.
   • AUC · full text, Section 'Genotype—Specific Pharmacokinetics After':The 7‐COOH CBD AUC0–∞ and C max were 32% and 53% higher in CYP3A5 NE respectively when compared to CYP3A5 Exp.
   • AUC · full text, Section 'Genotype—Specific Pharmacokinetics After':For 7‐COOH CBD, the AUC0–∞ was 66% higher in CYP2C19 IM/NM compared to RM/UM and the C max trended higher in CYP2C19 IM/NM compared to RM/UM.
   • AUC · full text, Section 'Genotype—Specific Pharmacokinetics at St':Mild differences were observed in 7‐OH CBD metabolite exposure for CYP2C19 IM/NM who had a 78% higher AUC0–τ and 96% higher C max compared to CYP2C19 RM/UM.
   • Form comparison · full text, Section 'Genotype—Specific Pharmacokinetics After':The 7‐OH CBD C max was 58% higher in CYP3A5 NE compared to Exp.
   • Form comparison · full text, Section 'Genotype—Specific Pharmacokinetics After':The 7‐COOH CBD AUC0–∞ and C max were 32% and 53% higher in CYP3A5 NE respectively when compared to CYP3A5 Exp.
   • Form comparison · full text, Section 'Genotype—Specific Pharmacokinetics After':For 7‐COOH CBD, the AUC0–∞ was 66% higher in CYP2C19 IM/NM compared to RM/UM and the C max trended higher in CYP2C19 IM/NM compared to RM/UM.
7. HumanPredicting Cannabidiol Pharmacokinetics in Older Adults Via Physiologically Based Pharmacokinetic Modeling.
   AAPS J, 2026 · Design: not stated · abstract only (PubMed) · open access (hybrid)
   PMID 42711610DOI 10.1208/s12248-026-01281-4
   Verification: abstract-only auto-extract; unverified
8. HumanThe acute and chronic pharmacokinetic oral fluid profile of oral cannabidiol (CBD) with and without low doses of delta-9-tetrahydrocannabinol (Δ9-THC) in healthy human volunteers.
   J Anal Toxicol, 2026 · Design: not stated · n: n = 10 · abstract only (PubMed) · closed/paywalled
   PMID 41252452DOI 10.1093/jat/bkaf102
   Verification: abstract-only auto-extract; unverified
9. HumanCannabidiol in Anorexia Nervosa: A Double-Blind Randomized Placebo Controlled Pilot Study to Test Safety, Pharmacokinetics, and Symptom Change.
   Int J Eat Disord, 2026 · Design: randomized; double-blind · n: n = 16 · full text (Europe PMC XML) + abstract · open access (hybrid)
   PMID 41906184DOI 10.1002/eat.70034PMC13326766 (free full text)
   Verification: full text read; no PK numbers matched
10. HumanRandomized single-dose crossover comparative bioavailability study of two novel oral cannabidiol (CBD) formulations in healthy volunteers under fed conditions, compared to a standard CBD isolate capsule.
    J Cannabis Res, 2025 · Design: randomized; crossover · abstract only (PubMed) · open access (gold)
    PMID 40770387DOI 10.1186/s42238-025-00312-9PMC12330118 (free full text)
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:All doses were administered 30 min after a standardized low-fat (~ 300-350 kcal, < 10 g fat) breakfast to minimize the impact of dietary fat on CBD absorption.
    • Key findings · abstract:Blood samples were collected up to 72 h post-dose for plasma CBD and 7-hydroxy-CBD analysis by a validated LC-MS/MS method (LLOQ 0.1 ng/mL).
    • Key findings · abstract:Pharmacokinetic (PK) parameters (C_max, tmax, AUC_0-72, and t_1/2) were determined by non-compartmental analysis.
    • Key findings · abstract:Plasma cortisol was measured pre-dose and at 2-, 4-, and 8-hours post-dose as an exploratory pharmacodynamic marker.
    • Key findings · abstract:The enhanced capsule achieved the highest peak CBD concentra[excerpt truncated in our database — see source]
    • Tmax · abstract:Pharmacokinetic (PK) parameters (C_max, tmax, AUC_0-72, and t_1/2) were determined by non-compartmental analysis.
    • Tmax · abstract:The time to peak concentration (tmax) was shortest for the liquid (median ~ 1.0 h), followed by the capsule (2.0 h), and longest for the reference (6.0 h).
    • Tmax · abstract:The 7-hydroxy-CBD metabolite reached much lower plasma levels than parent CBD for all treatments (C_max 0.4-1.8 ng/mL, ~ 5-13% of parent C_max), with a slightly delayed tmax (~ 2-6 h) and similar elimination half-life.
    • AUC · abstract:Pharmacokinetic (PK) parameters (C_max, tmax, AUC_0-72, and t_1/2) were determined by non-compartmental analysis.
    • AUC · abstract:The enhanced capsule achieved the highest peak CBD concentration (C_max 14.1 ng/mL) and exposure (AUC_0-72 38.0 h·ng/mL), compared to the enhanced liquid (C_max 6.2 ng/mL, AUC_0-72 20.2 h·ng/mL) and the reference capsule (C_max 2.4 ng/mL, AUC_0-72 11.7 h·ng/mL).
    • AUC · abstract:Inter-individual variability in C_max and AUC was substantially lower for both novel formulations (coefficients of variation ~ 27-44%) than for the reference (> 90%).
    • AUC · abstract:Statistical analysis confirmed that both the enhan
    • Relative bioavailability · abstract:The enhanced capsule in particular achieved a ~ 5.7-fold higher C_max and ~ 3.3-fold higher AUC than the reference, while the enhanced liquid was absorbed ~ 2.5-fold faster.
    • Fractional absorption · abstract:The enhanced capsule in particular achieved a ~ 5.7-fold higher C_max and ~ 3.3-fold higher AUC than the reference, while the enhanced liquid was absorbed ~ 2.5-fold faster.
    • Food effect · abstract:All doses were administered 30 min after a standardized low-fat (~ 300-350 kcal, < 10 g fat) breakfast to minimize the impact of dietary fat on CBD absorption.
11. HumanA Preliminary Pharmacokinetic Comparison of Δ-9 Tetrahydrocannabinol and Cannabidiol Extract Versus Oromucosal Spray in Healthy Men and Women.
    Cannabis Cannabinoid Res, 2025 · Design: randomized; crossover · abstract only (PubMed) · closed/paywalled
    PMID 39648730DOI 10.1089/can.2023.0249
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Our goal was to assess the pharmacokinetic parameters and relative bioavailability of two Δ9-tetrahydrocannabinol:cannabidiol (THC:CBD) formulations: orally administered THC:CBD extract and oromucosally administered nabiximols.
    • Relative bioavailability · abstract:Our goal was to assess the pharmacokinetic parameters and relative bioavailability of two Δ9-tetrahydrocannabinol:cannabidiol (THC:CBD) formulations: orally administered THC:CBD extract and oromucosally administered nabiximols.
    • Food effect · abstract:Results: Twelve occasional cannabis users (6 male, 6 female) were tested under fasting conditions.
12. HumanA high-fat meal significantly impacts the bioavailability and biphasic absorption of cannabidiol (CBD) from a CBD-rich extract in men and women.
    Sci Rep, 2025 · Design: randomized; crossover · n: n=5 · abstract (PubMed); full-text PDF saved · open access (gold)
    PMID 39880884DOI 10.1038/s41598-025-87621-4PMC11779803 (free full text)PDF
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:The geometric mean ratio (GMR) of CBD Cmax was 17.4 (90% CI 12.4-24.2 and of the AUC 9.7 (90% CI 7.7-12.3), demonstrating a substantial increase in peak concentration and total CBD exposure under fed conditions.
    • Key findings · abstract:This contributes to sustained high plasma concentrations and may be (partially) attributed to lymphatic transport, enterohepatic recirculation, and/or a secondary meal effect.This trial was registered on October 19, 2020, with ClinicalTrials.gov under the identifier NCT04589455.
    • Cmax · abstract:The geometric mean ratio (GMR) of CBD Cmax was 17.4 (90% CI 12.4-24.2 and of the AUC 9.7 (90% CI 7.7-12.3), demonstrating a substantial increase in peak concentration and total CBD exposure under fed conditions.
    • AUC · abstract:The geometric mean ratio (GMR) of CBD Cmax was 17.4 (90% CI 12.4-24.2 and of the AUC 9.7 (90% CI 7.7-12.3), demonstrating a substantial increase in peak concentration and total CBD exposure under fed conditions.
    • Food effect · abstract:The geometric mean ratio (GMR) of CBD Cmax was 17.4 (90% CI 12.4-24.2 and of the AUC 9.7 (90% CI 7.7-12.3), demonstrating a substantial increase in peak concentration and total CBD exposure under fed conditions.
13. HumanPopulation pharmacokinetics of cannabidiol and the impact of food and formulation on systemic exposure in children with drug-resistant developmental and epileptic encephalopathies.
    Epilepsia, 2025 · Design: not stated · n: N = 48 · abstract only (PubMed) · open access (green)
    PMID 39804155DOI 10.1111/epi.18255
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Simulated maximum plasma concentration (Cmax) and area under the concentration-time curve between 0 and 12 h (AUC0-12) were calculated.
    • Key findings · abstract:CBD Cmax increased by 41% and AUC0-12 by 45% when CBD was administered with food compared to fasting.
    • Key findings · abstract:Dose-normalized AUC0-12 was approximately 50% lower with CBD-enriched oil compared to purified CBD.
    • Cmax · abstract:Simulated maximum plasma concentration (Cmax) and area under the concentration-time curve between 0 and 12 h (AUC0-12) were calculated.
    • Cmax · abstract:CBD Cmax increased by 41% and AUC0-12 by 45% when CBD was administered with food compared to fasting.
    • AUC · abstract:Simulated maximum plasma concentration (Cmax) and area under the concentration-time curve between 0 and 12 h (AUC0-12) were calculated.
    • AUC · abstract:CBD Cmax increased by 41% and AUC0-12 by 45% when CBD was administered with food compared to fasting.
    • AUC · abstract:Dose-normalized AUC0-12 was approximately 50% lower with CBD-enriched oil compared to purified CBD.
    • Food effect · abstract:Serial blood samples were collected during maintenance treatment, before and after the morning dose, and up to 6 h after a dose of a purified CBD oil formulation, with or without a normocaloric breakfast.
    • Food effect · abstract:CBD Cmax increased by 41% and AUC0-12 by 45% when CBD was administered with food compared to fasting.
14. HumanThe Pharmacokinetics and Pharmacodynamics of a Hemp-Derived "Full-Spectrum" Oral Cannabinoid Product with a 1:1 Ratio of Cannabidiol to Cannabidiolic Acid and Delta-9-Tetrahydrocannabinol to Delta-9-Tetrahydrocannabinolic Acid: A Double-Blind, Placebo-Controlled, Within-Subjects Human Laboratory Study.
    Cannabis Cannabinoid Res, 2025 · Design: randomized · n: n = 15 · abstract only (PubMed) · closed/paywalled
    PMID 40040421DOI 10.1089/can.2024.0187
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Plasma specimens were collected throughout the 8-h sessions and at 24- and 48-h post-dosing.
    • Key findings · abstract:Dose-orderly increases in Cmax were observed for CBD, CBDA, THC, THCA, and their respective metabolites (e.g., 7-COOH-CBD, THCCOOH), which were often detectable 48 h post-dosing.
    • Key findings · abstract:Across all doses, Cmax for CBDA and THCA was 19-25-fold higher and Tmax was up to 2-fold earlier compared with CBD and THC, respectively.
    • Cmax · abstract:Dose-orderly increases in Cmax were observed for CBD, CBDA, THC, THCA, and their respective metabolites (e.g., 7-COOH-CBD, THCCOOH), which were often detectable 48 h post-dosing.
    • Cmax · abstract:Across all doses, Cmax for CBDA and THCA was 19-25-fold higher and Tmax was up to 2-fold earlier compared with CBD and THC, respectively.
    • Tmax · abstract:Across all doses, Cmax for CBDA and THCA was 19-25-fold higher and Tmax was up to 2-fold earlier compared with CBD and THC, respectively.
    • Relative bioavailability · abstract:Across all doses, Cmax for CBDA and THCA was 19-25-fold higher and Tmax was up to 2-fold earlier compared with CBD and THC, respectively.
15. HumanUsing a PBPK Model Incorporating Lymphatic Absorption to Predict Food Effect, Multiple Dosing, and Hepatic Impairment of Cannabidiol.
    Clin Transl Sci, 2025 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 41251333DOI 10.1111/cts.70401PMC12624468 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • AUC · full text, TABLE 1:Dose Model/Verification Absorption rate scalars Stomach MRT (h) Observed AUC0−t (h·ng/mL) Predicted AUC0−t (h·ng/mL) AUC Predicted: Observed Observed C max (ng/mL) Predicted C max (ng/mL) C max Predicted: Observed Observed t max (h) Predicted t max (h) t max Predicted: Observed References Single dose 200 mg oral V 1.00 Default 449.00 436.36 0.97 148.00 166.56 1.13 2.30 2.35 1.02 22 750 mg oral
    • Food effect · full text, Section ' PBPK Model Development':Small intestine MRTs for both fasted and fed states were increased by 45% from default values, accounting for the rich oleic acid content in sesame oil [26].
    • Food effect · full text, Section ' PBPK Model Development':Luminal bile salts for the fasted state were set to fed state values due to the presence of sesame oil, and the fed state values were further increased by 60%, calculated using the Simcyp default fed gallbladder residual volume (59.9%) and a reported gallbladder residual volume (36%) [27].
    • Food effect · full text, Section ' PBPK Model Development':When simulating a clinical trial where glucose was included during food intake, the lymph flow rate was set to 1.9 times that of the fasted state, based on a rat study [13].
16. HumanAn open-label phase I comparator-controlled clinical trial to assess tolerability and pharmacokinetics of IHL-675 A a fixed dose combination of cannabidiol plus hydroxychloroquine in healthy volunteers.
    Sci Rep, 2025 · Design: randomized · n: 12 participants · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 40456820DOI 10.1038/s41598-025-04573-5PMC12130181 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:Plasma concentrations of CBD, HCQ and their major metabolites, 7-OH-CBD, and 7-COOH-CBD, and desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylhydroxy-chloroquine (BDCQ) were assessed at predefined timepoints across the monitoring period and PK parameters were determined and compared between treatments using noncompartmental methods and analysis of variance (ANOVA) of log-transformed values exposure PK parameters.
    • Key findings · abstract:Both CBD and HCQ were bioavailable when dosed in IHL-675 A.
    • Key findings · abstract:There was approximately 50% increase in Cmax of CBD for IHL-675 A when compared with Epidio[excerpt truncated in our database — see source]
    • Cmax · abstract:There was approximately 50% increase in Cmax of CBD for IHL-675 A when compared with Epidiolex, and a slight increase of approximately 10% in AUC0-last and AUC0-inf.
    • Cmax · abstract:The 90% CI for the ratios of AUC0-inf, AUC0-last and Cmax of CBD all extended beyond the acceptance interval of 80% - 125%.
    • Cmax · abstract:The Cmax of HCQ for IHL-675 A was comparable to the reference product Plaquenil, with a geometric mean squares ratio of 96.5%.
    • Cmax · abstract:The 90% CI for the ratios of AUC0-last and Cmax of HCQ extended beyond the acceptance interval of 80% - 125%.
    • AUC · abstract:There was approximately 50% increase in Cmax of CBD for IHL-675 A when compared with Epidiolex, and a slight increase of approximately 10% in AUC0-last and AUC0-inf.
    • AUC · abstract:The 90% CI for the ratios of AUC0-inf, AUC0-last and Cmax of CBD all extended beyond the acceptance interval of 80% - 125%.
    • AUC · abstract:There was approximately 15% decrease in AUC0-last.
    • AUC · abstract:The 90% CI for the ratios of AUC0-last and Cmax of HCQ extended beyond the acceptance interval of 80% - 125%.
    • AUC · abstract:The ratio of AUC0-inf was not reliable for comparison between treatments, since the t1/2 was estimable for only 5 of 12 participants who rece
    • Cmax · full text, Table 5:Summary of key Cannabidiol PK parameters (PK analysis Set). Treatment(Number of participants) Median(Range) Arithmetic mean(CV%) Tmax(h) Cmax(ng/mL) AUC0−24(h*ng/mL) AUC0−last(h*ng/mL) AUC0−inf(h*ng/mL) T1/2(h) IHL-675 A(N = 12) 2.00(1.02–4.00) 207.04(59%) 551.0(52%) 806.3(45%) 841.0(45%) 220.17(26%) Epidiolex(N = 12) 2.50(1.50–6.00) 131.89(49%) 485.2(36%) 709.9(32%) 725.8a(33%) 231.22a(2
    • Cmax · full text, Table 6:Summary of key metabolite 7-OH-CBD PK parameters (PK analysis Set). Treatment(Number of participants) Median(Range) Arithmetic mean(CV%) Tmax(h) Cmax(ng/mL) AUC0−24(h*ng/mL) AUC0−last(h*ng/mL) AUC0−inf(h*ng/mL) T1/2(h) IHL-675 A(N = 12) 2.00(1.02–4.00) 55.24(65%) 276.5(55%) 386.0(55%) 389.1a(58%) 40.54a(137%) Epidiolex(N = 12) 2.52(1.50–6.00) 21.06(45%) 172.1(34%) 263.1(41%) 262.4a(42%) 21.15a(50
    • Cmax · full text, Table 7:Summary of key metabolite 7-COOH-CBD PK parameters (PK analysis Set). Treatment(Number of participants) Median(Range) Arithmetic mean(CV%) Tmax(h) Cmax(ng/mL) AUC0−24(h*ng/mL) AUC0−last(h*ng/mL) AUC0−inf(h*ng/mL) T1/2(h) IHL-675 A(N = 12) 2.50(1.50–6.00) 479.75(48%) 6353.4(44%) 17716.4(48%) 18753.9a(50%) 167.87a(60%) Epidiolex(N = 12) 6.00(2.50–6.00) 362.17(86%) 5310.1(72%) 15237.0(74%) 16267.9b(7
    • Tmax · full text, Table 5:Summary of key Cannabidiol PK parameters (PK analysis Set). Treatment(Number of participants) Median(Range) Arithmetic mean(CV%) Tmax(h) Cmax(ng/mL) AUC0−24(h*ng/mL) AUC0−last(h*ng/mL) AUC0−inf(h*ng/mL) T1/2(h) IHL-675 A(N = 12) 2.00(1.02–4.00) 207.04(59%) 551.0(52%) 806.3(45%) 841.0(45%) 220.17(26%) Epidiolex(N = 12) 2.50(1.50–6.00) 131.89(49%) 485.2(36%) 709.9(32%) 725.8a(33%) 2
    • Tmax · full text, Table 6:Summary of key metabolite 7-OH-CBD PK parameters (PK analysis Set). Treatment(Number of participants) Median(Range) Arithmetic mean(CV%) Tmax(h) Cmax(ng/mL) AUC0−24(h*ng/mL) AUC0−last(h*ng/mL) AUC0−inf(h*ng/mL) T1/2(h) IHL-675 A(N = 12) 2.00(1.02–4.00) 55.24(65%) 276.5(55%) 386.0(55%) 389.1a(58%) 40.54a(137%) Epidiolex(N = 12) 2.52(1.50–6.00) 21.06(45%) 172.1(34%) 263.1(41%) 262.4a(42%) 2
    • Tmax · full text, Table 7:Summary of key metabolite 7-COOH-CBD PK parameters (PK analysis Set). Treatment(Number of participants) Median(Range) Arithmetic mean(CV%) Tmax(h) Cmax(ng/mL) AUC0−24(h*ng/mL) AUC0−last(h*ng/mL) AUC0−inf(h*ng/mL) T1/2(h) IHL-675 A(N = 12) 2.50(1.50–6.00) 479.75(48%) 6353.4(44%) 17716.4(48%) 18753.9a(50%) 167.87a(60%) Epidiolex(N = 12) 6.00(2.50–6.00) 362.17(86%) 5310.1(72%) 15237.0(74%) 162
    • AUC · full text, Table 5:Summary of key Cannabidiol PK parameters (PK analysis Set). Treatment(Number of participants) Median(Range) Arithmetic mean(CV%) Tmax(h) Cmax(ng/mL) AUC0−24(h*ng/mL) AUC0−last(h*ng/mL) AUC0−inf(h*ng/mL) T1/2(h) IHL-675 A(N = 12) 2.00(1.02–4.00) 207.04(59%) 551.0(52%) 806.3(45%) 841.0(45%) 220.17(26%) Epidiolex(N = 12) 2.50(1.50–6.00) 131.89(49%) 485.2(36%) 709.9(32%) 725.8a(33%) 231.22a(26%)
    • AUC · full text, Table 6:of key metabolite 7-OH-CBD PK parameters (PK analysis Set). Treatment(Number of participants) Median(Range) Arithmetic mean(CV%) Tmax(h) Cmax(ng/mL) AUC0−24(h*ng/mL) AUC0−last(h*ng/mL) AUC0−inf(h*ng/mL) T1/2(h) IHL-675 A(N = 12) 2.00(1.02–4.00) 55.24(65%) 276.5(55%) 386.0(55%) 389.1a(58%) 40.54a(137%) Epidiolex(N = 12) 2.52(1.50–6.00) 21.06(45%) 172.1(34%) 263.1(41%) 262.4a(42%) 21.15a(50%)
    • AUC · full text, Table 7:f key metabolite 7-COOH-CBD PK parameters (PK analysis Set). Treatment(Number of participants) Median(Range) Arithmetic mean(CV%) Tmax(h) Cmax(ng/mL) AUC0−24(h*ng/mL) AUC0−last(h*ng/mL) AUC0−inf(h*ng/mL) T1/2(h) IHL-675 A(N = 12) 2.50(1.50–6.00) 479.75(48%) 6353.4(44%) 17716.4(48%) 18753.9a(50%) 167.87a(60%) Epidiolex(N = 12) 6.00(2.50–6.00) 362.17(86%) 5310.1(72%) 15237.0(74%) 16267.9b(71%) 153.6
    • Food effect · full text, Section 'Pharmacokinetic profile of IHL-675 A':This double peak phenomenon was also reported in a published study after a single oral dose of CBD (70 mg) post meal consumption, but not in the fasted state23.
    • Form comparison · full text, Section 'Pharmacokinetic profile of IHL-675 A':Following a single oral dose of IHL-675 A this study demonstrated that CBD had faster initial increase in plasma concentration, within the first 2 h for compared to the reference listed drug Epidiolex (Fig. 2a).
    • Form comparison · full text, Section 'Pharmacokinetic profile of IHL-675 A':There was approximately 50% increase in Cmax of CBD for IHL-675 A when compared with Epidiolex, and a slight increase of approximately 10% in AUC0−last and AUC0−inf.
    • Form comparison · full text, Section 'Pharmacokinetic profile of IHL-675 A':Conversely, HCQ in IHL-675 A demonstrated a slower initial absorption within the first 3 h for IHL-675 A compared to its RLD, Plaquenil (Fig. 2b).
17. HumanCannabidiol Bioavailability Is Nonmonotonic with a Long Terminal Elimination Half-Life: A Pharmacokinetic Modeling-Based Analysis.
    Cannabis Cannabinoid Res, 2025 · Design: not stated · abstract only (PubMed) · open access (hybrid)
    PMID 38624257DOI 10.1089/can.2023.0214
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Results: CBD was extensively distributed into tissue compartments with varied kinetics resulting in a long plasma terminal elimination half-life of >134 h in humans.
    • Key findings · abstract:For once-a-day oral dosing, the plasma trough concentrations require >70 days to reach a steady state.
18. HumanAssessment of intestinal absorption of five cannabinoids from an ethanolic CBD-rich hemp extract using Caco-2 cells in vitro.
    Toxicol In Vitro, 2025 · Design: not stated · abstract only (PubMed) · closed/paywalled
    PMID 40096897DOI 10.1016/j.tiv.2025.106053
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:We used Caco-2 cells in vitro to assess intestinal absorption of five cannabinoids (CBD, CBC, CBG, CBN, and CBDV) present in a CBD-rich hemp extract.
    • Key findings · abstract:This study highlights the challenges of evaluating permeability of cannabinoids by Caco-2 cells to predict intestinal absorption, including the physicochemical properties of these compounds, incubation time and cell properties.
19. HumanPhysiologically Based Pharmacokinetic Modeling of Cannabidiol, Delta-9-Tetrahydrocannabinol, and Their Metabolites in Healthy Adults After Administration by Multiple Routes.
    Clin Transl Sci, 2025 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 39748462DOI 10.1111/cts.70119PMC11695271 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:Predicted AUC and Cmax for CBD and 7-OH-CBD were within two-fold of the observed data.
    • Key findings · abstract:For THC, 11-OH-THC, and 11-COOH-THC, 100%, 100%, and 83% of the predicted AUC values were within two-fold, respectively, of the observed values; 100%, 92%, and 94% of the predicted Cmax values, respectively, were within two-fold of the observed values.
    • Cmax · abstract:Predicted AUC and Cmax for CBD and 7-OH-CBD were within two-fold of the observed data.
    • Cmax · abstract:For THC, 11-OH-THC, and 11-COOH-THC, 100%, 100%, and 83% of the predicted AUC values were within two-fold, respectively, of the observed values; 100%, 92%, and 94% of the predicted Cmax values, respectively, were within two-fold of the observed values.
    • AUC · abstract:Predicted AUC and Cmax for CBD and 7-OH-CBD were within two-fold of the observed data.
    • AUC · abstract:For THC, 11-OH-THC, and 11-COOH-THC, 100%, 100%, and 83% of the predicted AUC values were within two-fold, respectively, of the observed values; 100%, 92%, and 94% of the predicted Cmax values, respectively, were within two-fold of the observed values.
    • Relative bioavailability · abstract:Predicted AUC and Cmax for CBD and 7-OH-CBD were within two-fold of the observed data.
    • Relative bioavailability · abstract:For THC, 11-OH-THC, and 11-COOH-THC, 100%, 100%, and 83% of the predicted AUC values were within two-fold, respectively, of the observed values; 100%, 92%, and 94% of the predicted Cmax values, respectively, were within two-fold of the observed values.
    • AUC · full text, Section 'Results':All predicted 11‐OH‐THC plasma/blood AUC0‐t values were within two‐fold of the observed values, and 92% of the predicted C max were within two‐fold of the observations.
    • AUC · full text, Section 'Results':For the 11‐COOH‐THC verification dataset consisting of IV and inhalation studies, 83% and 94% of the predicted AUC0‐t and C max, respectively, were within two‐fold of the observed values.
20. HumanIn silico study of the pharmacokinetics and human and environmental toxicological analysis of cannabidiol.
    Braz J Biol, 2025 · Design: not stated · abstract only (PubMed) · open access (gold)
    PMID 40834136DOI 10.1590/1519-6984.291331
    Verification: abstract-only auto-extract; unverified
21. HumanPharmacokinetics and Side Effects of Δ9-Tetrahydrocannabinol and Cannabidiol in Patients with Different Stages of CKD.
    Kidney Int Rep, 2025 · Design: randomized · n: 29 patients · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 40225360DOI 10.1016/j.ekir.2024.12.030PMC11993231 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:The area under the curve (AUC) for THC (median [interquartile range]) was 2.76 (1.77-3.48), 4.16 (3.35-5.28), and 4.31 (3.16-5.42) h × ng/ml for controls, and for patients with CKD stages 4 and 5, respectively, with significant differences between patients with CKD and controls.
    • Key findings · abstract:After 1.5 hours, numeric rating scale (NRS) scores for dizziness were significantly higher for each CKD group compared with controls (mean NRSscores: 0.7 and 1.5 vs. 0.1).
    • Key findings · abstract:CONCLUSION: Total exposure to THC, CBD, and metabolites was higher in patients with CKD stages 4 and 5 compared with controls, and side effects[excerpt truncated in our database — see source]
    • AUC · abstract:The area under the curve (AUC) for THC (median [interquartile range]) was 2.76 (1.77-3.48), 4.16 (3.35-5.28), and 4.31 (3.16-5.42) h × ng/ml for controls, and for patients with CKD stages 4 and 5, respectively, with significant differences between patients with CKD and controls.
    • AUC · full text, Section 'Sample Size':A sample size calculation, based on a previous pharmacokinetic study of 2 sprays of Sativex in healthy volunteers,35 showed that 20 participants were required in each group (2 means) to detect a 50% change in AUC, with a significance level of 0.05, a power of 0.80, and an assumed 10% increase of the SD for patients with CKD.
22. HumanPharmacokinetic variability and use of therapeutic drug monitoring of cannabidiol in patients with refractory epilepsy.
    Epilepsia, 2025 · Design: not stated · n: 52 patients · abstract only (PubMed) · closed/paywalled
    PMID 39985501DOI 10.1111/epi.18284
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:METHODS: Data on serum concentrations of all ASMs, CBD, and the active metabolite 7-hydroxy-cannabidiol (7-OH-CBD) were collected (January 2022 to June 2023) at the Section for Clinical Pharmacology, National Centre for Epilepsy, Oslo University Hospital.
    • Key findings · abstract:RESULTS: Data from 52 patients were included: 122 serum concentration measurements (1-7 per patient); 48% female, mean age 23 (range 3-55) years.
    • Key findings · abstract:At maintenance (n = 34), the mean daily dose was 535 (SD 224) mg, that is, 10.03 (standard deviation [SD] .49) mg/kg/day, serum concentration .26 (SD .14) for CBD and .13 (SD .10) μmol/L for 7-O[excerpt truncated in our database — see source]
23. HumanEnhanced oral bioavailability and in vitro evaluation of cannabidiol camel milk-derived exosome formulation in resistant MDA-MB-231 and MDA-MB-468 breast cancer cells.
    Int J Pharm, 2024 · Design: not stated · abstract only (PubMed) · open access (bronze)
    PMID 38914353DOI 10.1016/j.ijpharm.2024.124375PMC12326876 (free full text)
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:The apparent permeability (Papp) of CBD-CMDE was found to be enhanced by 3.95-fold with Papp of 22.9*10-6 ± 0.34 cm/sec as compared to control CBD formulation with Papp of 5.8*10-6 ± 0.65 cm/sec in MDCK cells.
    • Key findings · abstract:In-vivo PK studies showed enhanced bioavailability of CBD from CBD-exosomes with AUC(0-24h) of 1350.56 ± 187.50 h.ng/mL as compared to CBD control formulation with AUC(0-24h) of 351.95 ± 39.10 h.ng/mL with a single oral dose of 12 mg/kg.
    • AUC · abstract:In-vivo PK studies showed enhanced bioavailability of CBD from CBD-exosomes with AUC(0-24h) of 1350.56 ± 187.50 h.ng/mL as compared to CBD control formulation with AUC(0-24h) of 351.95 ± 39.10 h.ng/mL with a single oral dose of 12 mg/kg.
    • Relative bioavailability · abstract:The apparent permeability (Papp) of CBD-CMDE was found to be enhanced by 3.95-fold with Papp of 22.9*10-6 ± 0.34 cm/sec as compared to control CBD formulation with Papp of 5.8*10-6 ± 0.65 cm/sec in MDCK cells.
24. HumanInfant formula as a solid lipid dose form for enhancement of the oral bioavailability of cannabidiol for paediatric patients.
    Int J Pharm, 2024 · Design: not stated · abstract only (PubMed) · open access (hybrid)
    PMID 38782154DOI 10.1016/j.ijpharm.2024.124257
    Verification: abstract-only auto-extract; unverified
25. HumanCannabidiol Oil Ingested as Sublingual Drops or Within Gelatin Capsules Shows Similar Pharmacokinetic Profiles in Healthy Males.
    Cannabis Cannabinoid Res, 2024 · Design: randomized; crossover · abstract only (PubMed) · open access (green)
    PMID 37733294DOI 10.1089/can.2023.0117
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Discussion: Plasma CBD concentrations were not different between CBD-Caps and CBD-Drops (interaction effect p=0.76).
    • Key findings · abstract:Cardiometabolic outcomes (plasma glucose/triacylglycerol, heart rate, blood pressure), liver function (plasma alanine aminotransferase/aspartate aminotransferase), kidney function (plasma creatinine), and subjective feelings/symptoms were not different between conditions (p≥0.07).
    • AUC · abstract:Peak CBD concentration (28.0±15.6 vs. 24.0±22.2 ng/mL), time of peak CBD concentration (4±1 vs. 4±2 h), and area under the concentration curve (45.3±20.3 vs. 41.8±23.3 ng/mL·6 h) were not different between conditions (p≥0.25).
26. HumanPharmacokinetic Variability of Oral Cannabidiol and Its Major Metabolites after Short-Term High-Dose Exposure in Healthy Subjects.
    Med Cannabis Cannabinoids, 2024 · Design: not stated · n: n = 12 · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 38292071DOI 10.1159/000535726PMC10824522 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:In the current study, plasma concentrations of CBD, 7-OH-CBD, and 7-COOH-CBD were measured, and the potential influences of sex, race, and body mass index (BMI) on the pharmacokinetic variability were assessed.
    • Key findings · abstract:Nine plasma samples were collected, and plasma concentrations of CBD, 7-OH-CBD, and 7-COOH-CBD were analyzed by LC-MS/MS.
    • Key findings · abstract:Statistical analysis was performed to determine the correlations of Cmax, AUC, and MPR of CBD, 7-OH-CBD, and 7-COOH-CBD in different sex, race, BMI, and body weight.
    • Key findings · abstract:RESULTS: For CBD, the mean Cmax was 389.17 ± 153.23 ng/mL, and the mean AUC was 1,542.19 ± 488.
    • Cmax · abstract:Statistical analysis was performed to determine the correlations of Cmax, AUC, and MPR of CBD, 7-OH-CBD, and 7-COOH-CBD in different sex, race, BMI, and body weight.
    • Cmax · abstract:RESULTS: For CBD, the mean Cmax was 389.17 ± 153.23 ng/mL, and the mean AUC was 1,542.19 ± 488.04 ng/mL*h.
    • Cmax · abstract:For 7-OH-CBD, the mean Cmax was 81.35 ± 36.64 ng/mL, the mean AUC was 364.70 ± 105.59 ng/mL*h, and the mean MPR was 0.25 ± 0.07.
    • Cmax · abstract:For 7-COOH-CBD, the mean Cmax was 1,717.33 ± 769.22 ng/mL, the mean AUC was 9,888.42 ± 3,961.47 ng/mL*h, and the mean MPR was 7.11 ± 3.48.
    • Cmax · abstract:For 7-COOH-CBD, a 2.25-fold higher Cmax was observe
    • AUC · abstract:Statistical analysis was performed to determine the correlations of Cmax, AUC, and MPR of CBD, 7-OH-CBD, and 7-COOH-CBD in different sex, race, BMI, and body weight.
    • AUC · abstract:RESULTS: For CBD, the mean Cmax was 389.17 ± 153.23 ng/mL, and the mean AUC was 1,542.19 ± 488.04 ng/mL*h.
    • AUC · abstract:For 7-OH-CBD, the mean Cmax was 81.35 ± 36.64 ng/mL, the mean AUC was 364.70 ± 105.59 ng/mL*h, and the mean MPR was 0.25 ± 0.07.
    • AUC · abstract:For 7-COOH-CBD, the mean Cmax was 1,717.33 ± 769.22 ng/mL, the mean AUC was 9,888.42 ± 3,961.47 ng/mL*h, and the mean MPR was 7.11 ± 3.48.
    • AUC · abstract:For 7-COOH-CBD, a 2.25-fold higher Cmax was observe
    • Relative bioavailability · abstract:For 7-COOH-CBD, a 2.25-fold higher Cmax was observed in female subjects (p = 0.0155) and a 1.97-fold higher AUC for female subjects (p = 0.0285) with the normalization of body weight.
    • Cmax · full text, Table 2.:H-CBD, and 7-COOH-CBD Compound Parameters Mean±SD Lower 95% CL for mean Upper 95% CL for mean Minimum Maximum CBD Tmax, h* 4±1.62 3.05 5.11 1.00 6.00 Cmax, ng/mL 389.17±153.23 291.81 486.52 177.00 648.00 AUC, ng/mL*h 1,542.19±488.04 1,232.10 1,852.28 737.30 2,331.00 7-OH-CBD Tmax (h)* 4±1.42 3.35 5.15 2.00 6.00 Cmax, ng/mL 81.35±36.64 58.07 104.63 30.00 173.00 AUC, ng/mL*h 364.70 ± 105.59 297.61 4
    • Cmax · full text, Section 'PK of CBD, 7-OH-CBD, and 7-COOH-CBD':For CBD, Tmax is 4 [1–6] h (median [min–max]), Cmax is 389.17 ± 153.23 ng/mL (mean ± SD), and AUC is 1,542.19 ± 488.04 ng/mL*h (mean ± SD).
    • Cmax · full text, Section 'PK of CBD, 7-OH-CBD, and 7-COOH-CBD':For 7-OH-CBD, Tmax is 4 [2–6] h (median [min–max]), Cmax is 81.35 ± 36.64 ng/mL (mean ± SD), AUC is 364.70 ± 105.59 ng/mL*h (mean ± SD), MPR is 0.25 ± 0.07 (mean ± SD).
    • Tmax · full text, Table 2.:-compartmental analysis for CBD, 7-OH-CBD, and 7-COOH-CBD Compound Parameters Mean±SD Lower 95% CL for mean Upper 95% CL for mean Minimum Maximum CBD Tmax, h* 4±1.62 3.05 5.11 1.00 6.00 Cmax, ng/mL 389.17±153.23 291.81 486.52 177.00 648.00 AUC, ng/mL*h 1,542.19±488.04 1,232.10 1,852.28 737.30 2,331.00 7-OH-CBD Tmax (h)* 4±1.42 3.35 5.15 2.00 6.00 Cmax, ng/mL 81.35±36.64 58.07 104.63 30.00 173.00 A
    • Tmax · full text, Section 'PK of CBD, 7-OH-CBD, and 7-COOH-CBD':For CBD, Tmax is 4 [1–6] h (median [min–max]), Cmax is 389.17 ± 153.23 ng/mL (mean ± SD), and AUC is 1,542.19 ± 488.04 ng/mL*h (mean ± SD).
    • Tmax · full text, Section 'PK of CBD, 7-OH-CBD, and 7-COOH-CBD':For 7-OH-CBD, Tmax is 4 [2–6] h (median [min–max]), Cmax is 81.35 ± 36.64 ng/mL (mean ± SD), AUC is 364.70 ± 105.59 ng/mL*h (mean ± SD), MPR is 0.25 ± 0.07 (mean ± SD).
    • AUC · full text, Table 2.:r 95% CL for mean Upper 95% CL for mean Minimum Maximum CBD Tmax, h* 4±1.62 3.05 5.11 1.00 6.00 Cmax, ng/mL 389.17±153.23 291.81 486.52 177.00 648.00 AUC, ng/mL*h 1,542.19±488.04 1,232.10 1,852.28 737.30 2,331.00 7-OH-CBD Tmax (h)* 4±1.42 3.35 5.15 2.00 6.00 Cmax, ng/mL 81.35±36.64 58.07 104.63 30.00 173.00 AUC, ng/mL*h 364.70 ± 105.59 297.61 431.79 188.10 554.20 MPR 0.25±0.07 0.20 0.29 0.16 0.36
    • AUC · full text, Section 'PK of CBD, 7-OH-CBD, and 7-COOH-CBD':For CBD, Tmax is 4 [1–6] h (median [min–max]), Cmax is 389.17 ± 153.23 ng/mL (mean ± SD), and AUC is 1,542.19 ± 488.04 ng/mL*h (mean ± SD).
    • AUC · full text, Section 'PK of CBD, 7-OH-CBD, and 7-COOH-CBD':For 7-OH-CBD, Tmax is 4 [2–6] h (median [min–max]), Cmax is 81.35 ± 36.64 ng/mL (mean ± SD), AUC is 364.70 ± 105.59 ng/mL*h (mean ± SD), MPR is 0.25 ± 0.07 (mean ± SD).
27. HumanCannabidiol Increases Psychotropic Effects and Plasma Concentrations of Δ9-Tetrahydrocannabinol Without Improving Its Analgesic Properties.
    Clin Pharmacol Ther, 2024 · Design: randomized; crossover; double-blind · n: 37 healthy volunteers · abstract (PubMed); full-text PDF saved · open access (hybrid)
    PMID 39054656DOI 10.1002/cpt.3381PDF
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:Administration of 450 mg CBD significantly increased AUClast of THC (AUClast ratio: 2.18, 95% CI: 1.54, 3.08, P < 0.0001) and 11-OH-THC (AUClast ratio: 6.24, 95% CI: 4.27, 9.12, P < 0.0001) compared with THC alone, and 30 mg CBD significantly increased AUClast of 11-OH-THC (AUClast ratio: 1.89, 95% CI: 1.30, 2.77, P = 0.0013), and of THC (AUClast ratio: 1.44, 95% CI: 1.01, 2.04, P = 0.0446).
    • AUC · abstract:Administration of 450 mg CBD significantly increased AUClast of THC (AUClast ratio: 2.18, 95% CI: 1.54, 3.08, P < 0.0001) and 11-OH-THC (AUClast ratio: 6.24, 95% CI: 4.27, 9.12, P < 0.0001) compared with THC alone, and 30 mg CBD significantly increased AUClast of 11-OH-THC (AUClast ratio: 1.89, 95% CI: 1.30, 2.77, P = 0.0013), and of THC (AUClast ratio: 1.44, 95% CI: 1.01, 2.04, P = 0.0446).
    • Cmax · full text, p.5:antly increased the AUClast of THC, 11-­ OH-­ T HC, not significantly affected by any treatment. Reaction time was and 11-­COOH-­T HC, as well as the Cmax of 11-­OH-­T HC significantly increased by THC with 450 mg CBD compared and 11-­ COOH-­ T HC, and significantly increased the with THC alone (Figure 1). metabolite-­to-­parent ratio for both THC metabolites, when 1292 VOLUME 116 NUMBER 5
    • Cmax · full text, PDF cbd_hemp_39054656.pdf:Novem
    • Cmax · full text, p.7:ite-­to-­ significantly increased the AUClast of THC, 11-­OH-­T HC, parent ratio for 11-­COOH-­T HC compared with administra- and 11-­COOH-­T HC, the Cmax of 11-­ OH-­T HC and tion of THC alone. The 10 mg CBD dose did not significantly 1294 VOLUME 116 NUMBER 5
    • Cmax · full text, PDF cbd_hemp_39054656.pdf:November 2024
    • Cmax · full text, PDF cbd_hemp_39054656.pdf:www.cpt-journal.com
    • Cmax · full text, p.13:­value) ratio vs. THC Estimated LSM 9 mg (95% CI), ratio vs. THC Parameter Treatment N LSM P-­value 9 mg (95% CI), Parameter Treatment N LSM P-­value Cmax THC 9 mg 27 31.46 – THC + CBD 10 mg 31 35.48 1.13 (0.95, THC 1.33), P = 0.1546 AUClast THC 9 mg 25 3.26 – THC + CBD 30 mg 29 38.60 1.23 (1.04, THC + CBD 10 mg 30 3.03 0.93 (0.66, 1.45), P = 0.0172 1.32), P = 0.6776 THC + CBD 28 80.60 2.56 (2.17,
    • Tmax · full text, p.3:ways adminis- tered 30 minutes prior to THC (or placebo) in order to align the expected of CBD could reduce the adverse effects of THC while not com- Tmax of the two compounds. The washout period between study visits was promising, or potentially even enhancing its analgesic properties. at least 14 days. Effects of THC alone were therefore compared with the combi- THC was administered in oral tabl
    • Tmax · full text, p.12:, the use of a validated pain test battery, and a formation of the active metabolite 11-­OH-­THC following oral dense PK sampling schedule around the Tmax resulted in a detailed administration of THC,49 and further elevation of 11-­OH-­THC assessment of oral THC/CBD interaction effects over time, both levels via CBD-­induced CYP inhibition. In contrast, compara- at the level of PK and PD, and the
    • AUC · full text, p.2:tly different from THC alone. CBD did not significantly enhance THC analgesia at any dose level. Administration of 450 mg CBD significantly increased AUClast of THC (AUClast ratio: 2.18, 95% CI: 1.54, 3.08, P < 0.0001) and 11-­OH-­THC (AUClast ratio: 6.24, 95% CI: 4.27, 9.12, P < 0.0001) compared with THC alone, and 30 mg CBD significantly increased AUClast of 11-­OH-­THC (AUClast ratio: 1.89, 95%
    • AUC · full text, p.4:with respect to THC and for 11-­COOH-­THC with re- inhibition. Two parameters were derived from the Stroop task: Stroop 1 spect to 11-­OH-­THC using AUClast estimates. relates to reaction time and Stroop 2 relates to the number of correct re- sponses. The simple reaction time (SRT) task is designed to measure the Sample size, randomization, and blinding attention and speed of information processin
    • AUC · full text, p.5:s on are provided in Table 3. Administration of 450 mg CBD sig- the Stroop task (both Stroop 1 and Stroop 2 parameters) were nificantly increased the AUClast of THC, 11-­ OH-­ T HC, not significantly affected by any treatment. Reaction time was and 11-­COOH-­T HC, as well as the Cmax of 11-­OH-­T HC significantly increased by THC with 450 mg CBD compared and 11-­ COOH-­ T HC, and significantly inc
    • Food effect · full text, p.3:ouble-­blind, randomized, double-­dummy placebo-­ Supplementary Materials. controlled, five-­way cross-­over study in which the effects of THC + pla- Fasting was required for at least 4 hours prior to every scheduled visit. cebo were compared with the effects of THC in combination with three Shortly after arrival, participants received a semi-­standardized light break- doses of CBD and double-­pla
    • Form comparison · full text, p.2:increased AUClast of THC (AUClast ratio: 2.18, 95% CI: 1.54, 3.08, P < 0.0001) and 11-­OH-­THC (AUClast ratio: 6.24, 95% CI: 4.27, 9.12, P < 0.0001) compared with THC alone, and 30 mg CBD significantly increased AUClast of 11-­OH-­THC (AUClast ratio: 1.89, 95% CI: 1.30, 2.77, P = 0.0013), and of THC (AUClast ratio: 1.44, 95% CI: 1.01, 2.04, P = 0.0446). Present findings do not support the use of C
    • Form comparison · full text, p.3:iod between study visits was promising, or potentially even enhancing its analgesic properties. at least 14 days. Effects of THC alone were therefore compared with the combi- THC was administered in oral tablets containing 1.5 mg THC nation of THC with three doses of CBD, controlled with a pla- (Namisol®) and CBD in oral tablets containing 20 mg or 150 mg cebo and a THC + placebo treatment arm. Su
    • Form comparison · full text, p.4:,31 Serum cortisol levels have been shown to increase after balanced Williams design randomization code was generated using SAS administration of THC compared with placebo in previous research.32 version 9.4 by a study-­independent statistician. 10 sequences were ran- domized in 3 blocks of 10, with 10 females in one block, 10 males in the Analgesic effects. During each treatment period, a validat
28. HumanPharmacokinetics and pharmacodynamics of five distinct commercially available hemp-derived topical cannabidiol products.
    J Anal Toxicol, 2024 · Design: not stated · n: N = 46 · abstract only (PubMed) · open access (bronze)
    PMID 38217086DOI 10.1093/jat/bkae001
    Verification: abstract-only auto-extract; unverified
29. HumanSex Differences in the Pharmacokinetics of Cannabidiol and Metabolites Following Oral Administration of a Cannabidiol-Dominant Cannabis Oil in Healthy Adults.
    Cannabis Cannabinoid Res, 2024 · Design: randomized; double-blind · n: n=17 · abstract only (PubMed) · closed/paywalled
    PMID 37267269DOI 10.1089/can.2022.0345
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:For metabolite-to-parent ratios (MPRs) of AUC0-t, there were significant effects of the sex×day interactions for 7-OH-CBD (F=6.89, p=0.016) and 7-COOH-CBD (F=5.96, p=0.021).
    • Key findings · abstract:For 7-COOH-CBD, follow-up analyses revealed significant simple effects of day within females (t=8.24, p<0.001) and males (t=5.20, p<0.001), therefore 7-COOH-CBD MPRs increased significantly from day 1 to 7 in both sexes, but the increase was significantly greater among females than among males.
    • AUC · abstract:For metabolite-to-parent ratios (MPRs) of AUC0-t, there were significant effects of the sex×day interactions for 7-OH-CBD (F=6.89, p=0.016) and 7-COOH-CBD (F=5.96, p=0.021).
30. HumanEvaluation of the efficacy, safety, and pharmacokinetics of nanodispersible cannabidiol oral solution (150 mg/mL) versus placebo in mild to moderate anxiety subjects: A double blind multicenter randomized clinical trial.
    Asian J Psychiatr, 2024 · Design: randomized · n: 178 participants · abstract only (PubMed) · open access (hybrid)
    PMID 38797087DOI 10.1016/j.ajp.2024.104073
    Verification: abstract-only auto-extract; unverified
31. HumanExamining the Systemic Bioavailability of Cannabidiol and Tetrahydrocannabinol from a Novel Transdermal Delivery System in Healthy Adults: A Single-Arm, Open-Label, Exploratory Study.
    Adv Ther, 2023 · Design: not stated · abstract only (PubMed) · open access (hybrid)
    PMID 36308640DOI 10.1007/s12325-022-02345-5PMC9859876 (free full text)
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Area-under-the-curve (AUC0-12 h), maximum concentration (Cmax), time to maximum concentration (Tmax), area-under-the-curve to infinity (AUCI), terminal elimination rate constant (λ), terminal half-life (t½), and absorption rate constant (ka) were measured individually for CBD and THC.
    • Key findings · abstract:RESULTS: AUC0-12 h for CBD and THC was 3329.8 ± 3252.1 and 2093.4 ± 2090.6 pg/mL/h, with Cmax of 576.52 ± 1016.18 and 346.57 ± 776.85 pg/mL, respectively.
    • Key findings · abstract:AUCI for CBD and THC was 6609.2 ± 7056.4 and 3721.0 ± 3251.7 pg/mL/h, with t1/2 of 5.68 ± 1.5 and 5.38 ± 1.25 h, respectively.
    • Key findings · abstract:CBD was absorbed at a fast[excerpt truncated in our database — see source]
    • Cmax · abstract:Area-under-the-curve (AUC0-12 h), maximum concentration (Cmax), time to maximum concentration (Tmax), area-under-the-curve to infinity (AUCI), terminal elimination rate constant (λ), terminal half-life (t½), and absorption rate constant (ka) were measured individually for CBD and THC.
    • Cmax · abstract:RESULTS: AUC0-12 h for CBD and THC was 3329.8 ± 3252.1 and 2093.4 ± 2090.6 pg/mL/h, with Cmax of 576.52 ± 1016.18 and 346.57 ± 776.85 pg/mL, respectively.
    • Tmax · abstract:Area-under-the-curve (AUC0-12 h), maximum concentration (Cmax), time to maximum concentration (Tmax), area-under-the-curve to infinity (AUCI), terminal elimination rate constant (λ), terminal half-life (t½), and absorption rate constant (ka) were measured individually for CBD and THC.
    • Tmax · abstract:Tmax for CBD and THC was 8 h, ranging from 2.5 h to 12 h and 10 min to 12 h, respectively.
    • AUC · abstract:Area-under-the-curve (AUC0-12 h), maximum concentration (Cmax), time to maximum concentration (Tmax), area-under-the-curve to infinity (AUCI), terminal elimination rate constant (λ), terminal half-life (t½), and absorption rate constant (ka) were measured individually for CBD and THC.
    • AUC · abstract:RESULTS: AUC0-12 h for CBD and THC was 3329.8 ± 3252.1 and 2093.4 ± 2090.6 pg/mL/h, with Cmax of 576.52 ± 1016.18 and 346.57 ± 776.85 pg/mL, respectively.
    • AUC · abstract:AUCI for CBD and THC was 6609.2 ± 7056.4 and 3721.0 ± 3251.7 pg/mL/h, with t1/2 of 5.68 ± 1.5 and 5.38 ± 1.25 h, respectively.
    • Fractional absorption · abstract:CBD was absorbed at a faster rate compared with THC (123.36 ± 530.97 versus 71.5 ± 1142.19 h-1) but with similar λ (0.12 ± 0.029 versus 0.13 ± 0.03 h-1).
32. HumanPharmacokinetics of Cannabidiol: A systematic review and meta-regression analysis.
    medRxiv, 2023 · Design: not stated · n: n=14 · abstract (PubMed); full-text PDF saved · open access (green)
    PMID 36778355DOI 10.1101/2023.02.01.23285341PMC9915832 (free full text)PDF
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:Trials of CBD in healthy adults were included if they reported at least one of the PK parameters of interest, including Tmax, Cmax, AUC0-t, AUC0-inf, and T 1/2 , in serum or plasma.
    • Key findings · abstract:A higher CBD dose was associated with higher Cmax, AUC0-t, and AUC0-inf.
    • Key findings · abstract:Compared to oral administration, oromucosal administration was associated with lower Cmax, AUC0-t, and AUC0-inf.
    • Key findings · abstract:Fed status was associated with higher Cmax and AUC0-t when compared to the fasting status.
    • Cmax · abstract:Trials of CBD in healthy adults were included if they reported at least one of the PK parameters of interest, including Tmax, Cmax, AUC0-t, AUC0-inf, and T 1/2 , in serum or plasma.
    • Cmax · abstract:A higher CBD dose was associated with higher Cmax, AUC0-t, and AUC0-inf.
    • Cmax · abstract:Compared to oral administration, oromucosal administration was associated with lower Cmax, AUC0-t, and AUC0-inf.
    • Cmax · abstract:Fed status was associated with higher Cmax and AUC0-t when compared to the fasting status.
    • Tmax · abstract:Trials of CBD in healthy adults were included if they reported at least one of the PK parameters of interest, including Tmax, Cmax, AUC0-t, AUC0-inf, and T 1/2 , in serum or plasma.
    • AUC · abstract:Trials of CBD in healthy adults were included if they reported at least one of the PK parameters of interest, including Tmax, Cmax, AUC0-t, AUC0-inf, and T 1/2 , in serum or plasma.
    • AUC · abstract:A higher CBD dose was associated with higher Cmax, AUC0-t, and AUC0-inf.
    • AUC · abstract:Compared to oral administration, oromucosal administration was associated with lower Cmax, AUC0-t, and AUC0-inf.
    • AUC · abstract:Fed status was associated with higher Cmax and AUC0-t when compared to the fasting status.
    • Food effect · abstract:Fed status was associated with higher Cmax and AUC0-t when compared to the fasting status.
    • Cmax · full text, p.2:p to November 19, 2022. Trials of CBD in healthy adults were included if they reported at least one of the PK parameters of interest, including Tmax, Cmax, AUC0-t, AUC0-inf, and T1/2, in serum or plasma. Studies of patient populations or CBD co-administration with other medications were excluded. The National Heart, Lung, and Blood Institute’s Quality Assessment Tool for Before-After Studies with
    • Cmax · full text, p.4:ssion models. There were five PK parameters of interest: 1. Tmax: time from CBD administration to the maximum concentration of CBD in plasma/serum 2. Cmax: maximum concentration of CBD in plasma/serum 3. AUC0-t: the area under the curve of serum/plasma concentrations plotted against time from CBD administration to a specific time-point, usually the end of the PK session 4. AUC0-inf: the extrapolat
    • Cmax · full text, p.8:in oromucosal, and 0.42-6000mg in oral administration (Table 1). The duration of the PK session was between 4-164 h. All trial arms reported Tmax and Cmax except one that did not report any values, 96 reported AUC0-t, 59 reported AUC0-inf, and 60 reported T1/2. Only 22 treatment arms from four studies reported Cmax and AUC in geometric scale (Supplement Table1 and Supplement Showcase). At least on
    • Tmax · full text, p.2:tion up to November 19, 2022. Trials of CBD in healthy adults were included if they reported at least one of the PK parameters of interest, including Tmax, Cmax, AUC0-t, AUC0-inf, and T1/2, in serum or plasma. Studies of patient populations or CBD co-administration with other medications were excluded. The National Heart, Lung, and Blood Institute’s Quality Assessment Tool for Before-After Studies
    • Tmax · full text, p.4:ially influence PK parameters, based on the available literature resulting from meta-regression models. There were five PK parameters of interest: 1. Tmax: time from CBD administration to the maximum concentration of CBD in plasma/serum 2. Cmax: maximum concentration of CBD in plasma/serum 3. AUC0-t: the area under the curve of serum/plasma concentrations plotted against time from CBD administrati
    • Tmax · full text, p.8:, 5-50mg in oromucosal, and 0.42-6000mg in oral administration (Table 1). The duration of the PK session was between 4-164 h. All trial arms reported Tmax and Cmax except one that did not report any values, 96 reported AUC0-t, 59 reported AUC0-inf, and 60 reported T1/2. Only 22 treatment arms from four studies reported Cmax and AUC in geometric scale (Supplement Table1 and Supplement Showcase). At
    • AUC · full text, p.2:ovember 19, 2022. Trials of CBD in healthy adults were included if they reported at least one of the PK parameters of interest, including Tmax, Cmax, AUC0-t, AUC0-inf, and T1/2, in serum or plasma. Studies of patient populations or CBD co-administration with other medications were excluded. The National Heart, Lung, and Blood Institute’s Quality Assessment Tool for Before-After Studies with no Con
    • AUC · full text, p.4:t: 1. Tmax: time from CBD administration to the maximum concentration of CBD in plasma/serum 2. Cmax: maximum concentration of CBD in plasma/serum 3. AUC0-t: the area under the curve of serum/plasma concentrations plotted against time from CBD administration to a specific time-point, usually the end of the PK session 4. AUC0-inf: the extrapolation of AUC0-t to the infinity time point 5. Half-life,
    • AUC · full text, p.8:1). The duration of the PK session was between 4-164 h. All trial arms reported Tmax and Cmax except one that did not report any values, 96 reported AUC0-t, 59 reported AUC0-inf, and 60 reported T1/2. Only 22 treatment arms from four studies reported Cmax and AUC in geometric scale (Supplement Table1 and Supplement Showcase). At least one PK parameter from each and all treatment arms needed to go
    • Food effect · full text, p.2:h higher Cmax, AUC0-t, and AUC0-inf. Compared to oral administration, oromucosal administration was associated with lower Cmax, AUC0-t, and AUC0-inf. Fed status was associated with higher Cmax and AUC0-t when compared to the fasting status. A higher ratio of female participants was associated with lower Tmax in oral administration and higher Cmax. Conclusion: As expected, CBD dose, route of admini
    • Food effect · full text, p.4:on of the drug in the plasma to be reduced by 50%. Potential variables of interest were: route of administration, CBD dose, CBD formulation, dietary (fasting/fed) status before CBD administration, abstinence from cannabis before CBD administration, sex, and duration of the PK session 3,5,6. Inclusion/exclusion criteria Trials of any design were considered for inclusion if conducted on healthy adul
    • Food effect · full text, p.8:6 arms. Participants’ sex was not clearly reported for 10 arms. Participants were abstinent from cannabis before study initiation in 105 arms and had fasted before CBD administration in 63 arms. Eight arms used inhalation as the route of administration, 29 oromucosal, 73 oral, and 2 intravenous. A variety of formulations were used consisting of nanotech (n=14), oil-based (n=21), alcohol-based (n=1
    • Form comparison · full text, p.2:r of males than females. The duration of the PK session was between 4h-164h. A higher CBD dose was associated with higher Cmax, AUC0-t, and AUC0-inf. Compared to oral administration, oromucosal administration was associated with lower Cmax, AUC0-t, and AUC0-inf. Fed status was associated with higher Cmax and AUC0-t when compared to the fasting status. A higher ratio of female participants was asso
    • Form comparison · full text, p.9:variables. Higher CBD dose was consistently associated with higher Cmax, AUC0-t, and AUC0-inf across all models (Table 4; Figure 2; Suppl Figure 1). Compared to oral administration as a reference, inhalation was associated with lower Tmax in a poorly-fitted model (Table 4, Model# 1,2), but did not show any significant difference for Cmax (Model# 7,8), AUC0-t (Model# 13,14), or AUC0-inf (Model#19).
    • Form comparison · full text, p.11:t fed condition was associated with a higher bioavailability of CBD, but had no significant impact in the time to reach maximum serum concentrations, compared to the fasted status. Specifically, we observed a higher Cmax and AUC0-t across all the models for fed condition compared to fast status, which is in line with within-study direct comparisons 12,19,34,40 . The lack of a significant effect of
33. HumanAssessment of Orally Administered Δ9-Tetrahydrocannabinol When Coadministered With Cannabidiol on Δ9-Tetrahydrocannabinol Pharmacokinetics and Pharmacodynamics in Healthy Adults: A Randomized Clinical Trial.
    JAMA Netw Open, 2023 · Design: randomized; crossover; double-blind · n: 18 adults · abstract only (PubMed) · not checked (off-topic)
    PMID 36780161DOI 10.1001/jamanetworkopen.2022.54752PMC9926328 (free full text)
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:MAIN OUTCOMES AND MEASURES: Change-from-baseline plasma concentrations for Δ9-THC or Δ9-THC metabolites and scores for subjective drug effects, cognitive and psychomotor performance, and vital signs.
    • Key findings · abstract:Relative to CYP cocktail + Δ9-THC, CYP cocktail + Δ9-THC + CBD produced a higher Cmax and area under the plasma concentration vs time curve for Δ9-THC, 11-OH-Δ9-THC, and Δ9-THC-COOH.
    • Cmax · abstract:Relative to CYP cocktail + Δ9-THC, CYP cocktail + Δ9-THC + CBD produced a higher Cmax and area under the plasma concentration vs time curve for Δ9-THC, 11-OH-Δ9-THC, and Δ9-THC-COOH.
    • AUC · abstract:Relative to CYP cocktail + Δ9-THC, CYP cocktail + Δ9-THC + CBD produced a higher Cmax and area under the plasma concentration vs time curve for Δ9-THC, 11-OH-Δ9-THC, and Δ9-THC-COOH.
34. HumanPopulation Pharmacokinetics of Oral-Based Administration of Cannabidiol in Healthy Adults: Implications for Drug Development.
    Cannabis Cannabinoid Res, 2023 · Design: randomized; crossover · n: n=12 · abstract only (PubMed) · closed/paywalled
    PMID 35443784DOI 10.1089/can.2021.0202
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Simulations indicated a 3.6-fold difference in drug exposure at steady state with multiple dosing (AUCτ 95% prediction interval: 65.5-138 ng·h/mL), and variability in the time to reach steady state, which was predicted to be up to ∼3 weeks in some individuals (95% prediction interval: 18.6-297 h).
    • AUC · abstract:Simulations indicated a 3.6-fold difference in drug exposure at steady state with multiple dosing (AUCτ 95% prediction interval: 65.5-138 ng·h/mL), and variability in the time to reach steady state, which was predicted to be up to ∼3 weeks in some individuals (95% prediction interval: 18.6-297 h).
    • Relative bioavailability · abstract:Simulations indicated a 3.6-fold difference in drug exposure at steady state with multiple dosing (AUCτ 95% prediction interval: 65.5-138 ng·h/mL), and variability in the time to reach steady state, which was predicted to be up to ∼3 weeks in some individuals (95% prediction interval: 18.6-297 h).
35. HumanVerifying in vitro-determined enzyme contributions to cannabidiol clearance for exposure predictions in human through physiologically-based pharmacokinetic modeling.
    CPT Pharmacometrics Syst Pharmacol, 2023 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 36540909DOI 10.1002/psp4.12908PMC10014054 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:Linear mixed effect modeling was used to estimate area under the concentration-time curve from zero to infinity (AUC0-∞ ) perpetrator + CBD versus CBD alone.
    • Key findings · abstract:The i.v. and oral datasets used in model evaluation produced acceptable average fold error (AFE) of 1.28 and absolute AFE of 1.65.
    • Key findings · abstract:The simulated DDI studies using the in vitro-derived values produced AUC0-∞ treatment ratios comparable to observed: itraconazole 1.24 versus 1.07, fluconazole 1.45 versus 1.22, and rifampicin 0.49 versus 0.69.
    • AUC · abstract:Linear mixed effect modeling was used to estimate area under the concentration-time curve from zero to infinity (AUC0-∞ ) perpetrator + CBD versus CBD alone.
    • AUC · abstract:The simulated DDI studies using the in vitro-derived values produced AUC0-∞ treatment ratios comparable to observed: itraconazole 1.24 versus 1.07, fluconazole 1.45 versus 1.22, and rifampicin 0.49 versus 0.69.
    • Relative bioavailability · abstract:The i.v. and oral datasets used in model evaluation produced acceptable average fold error (AFE) of 1.28 and absolute AFE of 1.65.
    • AUC · full text, Section 'Oral PBPK model construction and evaluat':Additionally, the oral model predicted area under the plasma concentration‐time curve from time point 0 to the end of the dosing interval (AUC0‐τ) were compared to observed values (development and evaluation datasets) by calculating the percent difference, attained by (observed – predicted)/observed × 100%.
    • AUC · full text, Section 'Oral PBPK models':The oral model predicted AUC0‐τ compared to those observed were well captured, resulting in a mean [range] percent difference of −8.54% [−90 to 28%].
    • AUC · full text, Section ' DDI simulations':The calculated percent error comparing the predicted and observed AUC0–∞ geometric mean treatment ratios were 16%, 19%, and 29% for itraconazole, fluconazole, and rifampicin, respectively.
    • Food effect · full text, Section 'Clinical DDI studies simulation':To create a population of subjects who were administered CBD in the fed state, 100 individuals were built based on the sex, age, and weight distributions reported by Patsalos et al. 10 The virtual subjects were given a single dose of 750 mg CBD oral solution after 30 min of a high‐fat breakfast for the CBD alone arm.
    • Food effect · full text, Section 'Oral PBPK models':The study by Morrison et al. 36 was used to evaluate the fed state model with 750 mg oral solution administered every other day.
    • Food effect · full text, Section 'Oral PBPK models':In the studies by Taylor et al., 5 an oral solution dose was administered in the morning after 10 h of fasting and administered again in the evening 2 h after the end of a meal.
    • Form comparison · full text, Section 'Oral PBPK model construction and evaluat':Additionally, the oral model predicted area under the plasma concentration‐time curve from time point 0 to the end of the dosing interval (AUC0‐τ) were compared to observed values (development and evaluation datasets) by calculating the percent difference, attained by (observed – predicted)/observed × 100%.
    • Form comparison · full text, Section 'Oral PBPK models':The oral model predicted AUC0‐τ compared to those observed were well captured, resulting in a mean [range] percent difference of −8.54% [−90 to 28%].
    • Form comparison · full text, TABLE 1:Physicochemical properties and ADME of CBD for i.v. model construction Used in naïve model Used in optimized model Physicochemical properties Lipophilicity (logP) 6.1 log units (ALOGPS), 6.3 log units (ChemAxon) 6 2.43 log units Fraction unbound in plasma (f u) 0.06–0.07, 44 , 45 0.18 43 0.18 Fraction excreted in urine, feces 0.16, 0.12 (unchanged) 3 0.16, 0.12 (unchanged) Molecular weigh
36. HumanPharmacokinetics of cannabidiol-/cannabidiolic acid-rich hemp oil in juvenile cynomolgus macaques (Macaca fascicularis).
    Front Vet Sci, 2023 · Design: not stated · n: n = 4 · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 38094499DOI 10.3389/fvets.2023.1286158PMC10716325 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:METHODS: After a 2 mg/kg CBD/ArHO pilot study, 4 and 8 mg/kg direct-to-mouth CBD/ArHO were administered (n = 4 per dose) once daily for 14 days and blood was collected at 0-, 0.5-, 1-, 2-, 4-, 8-, 12-, and 24-h, and on Days 7 and 14, to quantify serum cannabinoid concentrations by high-performance liquid chromatography-tandem mass spectrometry.
    • Key findings · abstract:Serum biochemistries and complete blood counts were performed on Days 0, 1, and 14.
    • Key findings · abstract:RESULTS: The maximum mean serum concentration (Cmax) of CBDA was 28.6-36.2 times that of CBD at 4 and 8 mg/kg.
    • Key findings · abstract:At 8 mg/kg, the Cmax of CBD was 1.4 times higher (p[excerpt truncated in our database — see source]
    • Cmax · abstract:RESULTS: The maximum mean serum concentration (Cmax) of CBDA was 28.6-36.2 times that of CBD at 4 and 8 mg/kg.
    • Cmax · abstract:At 8 mg/kg, the Cmax of CBD was 1.4 times higher (p = 0.0721), and CBDA was significantly 1.8 times higher (p = 0.0361), than at 4 mg/kg.
    • Cmax · full text, Table 2:istration of cannabidiol-/cannabidiolic acid-rich hemp oil at 4 or 8 mg/kg to juvenile cynomolgus macaques (n = 4 per dose) over 24 h. Cannabinoid R2 Cmax (ng/mL) Tmax (h) t1/2–λz (h) AUClast (h·ng/mL) AUMClast (h2·ng/mL) MRTlast (h) 4 mg/kg CBD 0.9124 15.98 ± 11.07 1 5.57 75.12 437.71 5.83 CBDA 0.9417 456.75 ± 187.48 0.5 6.80 838.28 3264.70 3.89 THC 0.9989 3.94 ± 2.42 1 1.94 12.50 33.03 2.64 THCA
    • Cmax · full text, Section 'Serum cannabinoids':The Cmax was 1.4 times higher at 8 mg/kg than at 4 mg/kg.
    • Cmax · full text, Section 'Serum cannabinoids':At 4 mg/kg, the Cmax for one animal was at least 5.0 times higher than any other individual Cmax, and 8.0 times higher than any other animal at the 1-h timepoint.
    • Tmax · full text, Table 2:cannabidiol-/cannabidiolic acid-rich hemp oil at 4 or 8 mg/kg to juvenile cynomolgus macaques (n = 4 per dose) over 24 h. Cannabinoid R2 Cmax (ng/mL) Tmax (h) t1/2–λz (h) AUClast (h·ng/mL) AUMClast (h2·ng/mL) MRTlast (h) 4 mg/kg CBD 0.9124 15.98 ± 11.07 1 5.57 75.12 437.71 5.83 CBDA 0.9417 456.75 ± 187.48 0.5 6.80 838.28 3264.70 3.89 THC 0.9989 3.94 ± 2.42 1 1.94 12.50 33.03 2.64 THCA 0.9464 41.90
    • Tmax · full text, Section 'Serum cannabinoids':The Tmax occurred at 1 h at 4 mg/kg, and 2 h at 8 mg/kg.
    • Tmax · full text, Section 'Serum cannabinoids':At 8 mg/kg, the Cmax for one animal was at least 1.9 times lower, and its Tmax was at least 6 h later, than any other individual.
    • AUC · full text, Table 2:iolic acid-rich hemp oil at 4 or 8 mg/kg to juvenile cynomolgus macaques (n = 4 per dose) over 24 h. Cannabinoid R2 Cmax (ng/mL) Tmax (h) t1/2–λz (h) AUClast (h·ng/mL) AUMClast (h2·ng/mL) MRTlast (h) 4 mg/kg CBD 0.9124 15.98 ± 11.07 1 5.57 75.12 437.71 5.83 CBDA 0.9417 456.75 ± 187.48 0.5 6.80 838.28 3264.70 3.89 THC 0.9989 3.94 ± 2.42 1 1.94 12.50 33.03 2.64 THCA 0.9464 41.90 ± 12.77 1 4.60 204.6
    • AUC · full text, Section 'Serum cannabinoids':At 8 mg/kg, the AUClast was 2.1 times, and the AUMClast was 2.2 times, higher than at 4 mg/kg.
    • AUC · full text, Section 'Serum cannabinoids':At 8 mg/kg, the AUClast was 3.3 times, and the AUMClast was 3.9 times, higher than at 4 mg/kg.
    • Relative bioavailability · full text, Section 'Serum cannabinoids':The Cmax was 1.4 times higher at 8 mg/kg than at 4 mg/kg.
    • Relative bioavailability · full text, Section 'Serum cannabinoids':At 4 mg/kg, the Cmax for one animal was at least 5.0 times higher than any other individual Cmax, and 8.0 times higher than any other animal at the 1-h timepoint.
    • Relative bioavailability · full text, Section 'Serum cannabinoids':The Cmax was 1.8 times higher at 8 mg/kg than at 4 mg/kg.
    • Form comparison · full text, Section 'Serum biochemistry and complete blood co':The mean AST was 1.9–2.5 times higher at Day 1 compared to Day 0 and Day 14; one individual at 4 mg/kg and two individuals at 8 mg/kg were higher than the recommended reference range at Day 1.
    • Form comparison · full text, Section 'Serum cannabinoids':One PK analysis in dogs at 8 mg/kg had a Cmax for CBD of 591 ng/mL (28), 26.5 times higher than in our subjects, indicating a higher absorption and bioavailability, or differences in metabolism, distribution, or elimination, compared to cynomolgus macaques.
37. HumanCannabidiol nanoemulsion for eye treatment - Anti-inflammatory, wound healing activity and its bioavailability using in vitro human corneal substitute.
    Int J Pharm, 2023 · Design: not stated · abstract only (PubMed) · open access (hybrid)
    PMID 37406946DOI 10.1016/j.ijpharm.2023.123202
    Verification: abstract-only auto-extract; unverified
38. HumanA One Health perspective on comparative cannabidiol and cannabidiolic acid pharmacokinetics and biotransformation in humans and domestic animals.
    Am J Vet Res, 2023 · Design: not stated · abstract only (PubMed) · open access (gold)
    PMID 36972696DOI 10.2460/ajvr.23.02.0031
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:With a knowledge of the desired serum concentration for optimum pharmacological effect, the amount and rate of drug administration can be tailored to maintain that concentration based on the 24-hour PK modeling (eg, every 24 hours, every 12 hours) to achieve therapeutic ranges.
39. HumanA Physiologically-Based Pharmacokinetic Model for Cannabidiol in Healthy Adults, Hepatically-Impaired Adults, and Children.
    Drug Metab Dispos, 2023 · Design: not stated · abstract only (PubMed) · open access (green)
    PMID 36972999DOI 10.1124/dmd.122.001128PMC10197200 (free full text)
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Our PBPK model successfully predicted CBD systemic exposure in both populations within 0.5- to 2-fold of the observed values.
    • Relative bioavailability · abstract:Our PBPK model successfully predicted CBD systemic exposure in both populations within 0.5- to 2-fold of the observed values.
40. HumanA Randomized, Triple-Blind, Comparator-Controlled Parallel Study Investigating the Pharmacokinetics of Cannabidiol and Tetrahydrocannabinol in a Novel Delivery System, Solutech, in Association with Cannabis Use History.
    Cannabis Cannabinoid Res, 2022 · Design: randomized · full text (Europe PMC XML) + abstract · open access (hybrid)
    PMID 35787693DOI 10.1089/can.2021.0176PMC9784610 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:Results: Acute consumption of Solutech provided a significantly greater maximum concentration (Cmax), larger elimination and absorption rate constants, faster time to Cmax and lag time, and half-life for all analytes compared to MCT-oil (p<0.001).
    • Key findings · abstract:On average, participants with later age of first use had higher Δ9-THC, CBD, and THC-COOH Cmax and later time-to-Cmax and half-life for Δ9-THC, CBD, THC-COOH, and 11-OH-THC than those with earlier age of first use (p≤0.032).
    • Key findings · abstract:Those with more years of recreational cannabis use had higher area under the curve for Δ9-THC and CBD, Cmax for CBD, and lo[excerpt truncated in our database — see source]
    • Cmax · abstract:Results: Acute consumption of Solutech provided a significantly greater maximum concentration (Cmax), larger elimination and absorption rate constants, faster time to Cmax and lag time, and half-life for all analytes compared to MCT-oil (p<0.001).
    • Cmax · abstract:On average, participants with later age of first use had higher Δ9-THC, CBD, and THC-COOH Cmax and later time-to-Cmax and half-life for Δ9-THC, CBD, THC-COOH, and 11-OH-THC than those with earlier age of first use (p≤0.032).
    • Cmax · abstract:Those with more years of recreational cannabis use had higher area under the curve for Δ9-THC and CBD, Cmax for CBD, and lo
    • AUC · abstract:Those with more years of recreational cannabis use had higher area under the curve for Δ9-THC and CBD, Cmax for CBD, and longer 11-OH-THC half-life than those with less (p≤0.048).
    • Cmax · full text, Section 'Cannabidiol':CBD Cmax was 1.2 ng/mL greater, tmax was 4.1 h faster, and tlag was 2.1 h faster compared to MCT-oil.
    • Cmax · full text, Section '11-OH-THC and THC-COOH':With Solutech, the Cmax of the Δ9-THC metabolites, 11-OH-THC and THC-COOH, was 2.4 and 23.5 ng/mL greater, respectively.
    • Tmax · full text, Section 'Tetrahydrocannabinol':As well, maximum Δ9-THC concentration was 2.5 ng/mL greater, tmax was 4.4 h faster, and tlag was 1.5 h faster compared to MCT-oil.
    • Tmax · full text, Section 'Cannabidiol':CBD Cmax was 1.2 ng/mL greater, tmax was 4.1 h faster, and tlag was 2.1 h faster compared to MCT-oil.
    • Tmax · full text, Section '11-OH-THC and THC-COOH':The Tmax of 11-OH-THC and THC-COOH was 4.1h faster, with Solutech.
    • Form comparison · full text, Section 'Tetrahydrocannabinol':As well, maximum Δ9-THC concentration was 2.5 ng/mL greater, tmax was 4.4 h faster, and tlag was 1.5 h faster compared to MCT-oil.
    • Form comparison · full text, Section 'Cannabidiol':CBD Cmax was 1.2 ng/mL greater, tmax was 4.1 h faster, and tlag was 2.1 h faster compared to MCT-oil.
41. HumanPharmacokinetics of cannabichromene in a medical cannabis product also containing cannabidiol and Δ9-tetrahydrocannabinol: a pilot study.
    Eur J Clin Pharmacol, 2022 · Design: randomized · n: N = 43 · full text (Europe PMC XML) + abstract · open access (hybrid)
    PMID 34664109DOI 10.1007/s00228-021-03232-8PMC8748343 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:RESULTS: After a single dose and after the final dose, the Cmax of CBC increased by 1.3-1.8-fold for each twofold increase in dose; the tmax range was 1.6-4.3 h.
    • Key findings · abstract:Based on the ratio of administered CBD, THC, and CBC to the plasma concentration, the dose of CBD was 18 times higher than the dose of CBC, yet the AUC0-t of CBD was only 6.6-9.8-fold higher than the AUC0-t of CBC; the dose of THC was similar to the dose of CBC, yet THC was quantifiable in fewer plasma samples than was CBC.
    • Cmax · abstract:RESULTS: After a single dose and after the final dose, the Cmax of CBC increased by 1.3-1.8-fold for each twofold increase in dose; the tmax range was 1.6-4.3 h.
    • Tmax · abstract:RESULTS: After a single dose and after the final dose, the Cmax of CBC increased by 1.3-1.8-fold for each twofold increase in dose; the tmax range was 1.6-4.3 h.
    • AUC · abstract:Based on the ratio of administered CBD, THC, and CBC to the plasma concentration, the dose of CBD was 18 times higher than the dose of CBC, yet the AUC0-t of CBD was only 6.6-9.8-fold higher than the AUC0-t of CBC; the dose of THC was similar to the dose of CBC, yet THC was quantifiable in fewer plasma samples than was CBC.
    • Relative bioavailability · abstract:RESULTS: After a single dose and after the final dose, the Cmax of CBC increased by 1.3-1.8-fold for each twofold increase in dose; the tmax range was 1.6-4.3 h.
    • Relative bioavailability · abstract:Based on the ratio of administered CBD, THC, and CBC to the plasma concentration, the dose of CBD was 18 times higher than the dose of CBC, yet the AUC0-t of CBD was only 6.6-9.8-fold higher than the AUC0-t of CBC; the dose of THC was similar to the dose of CBC, yet THC was quantifiable in fewer plasma samples than was CBC.
    • Cmax · full text, Table 2:parameter (unit) Treatment Aa (n = 8) Treatment Ba (n = 8) Treatment Ca (n = 8) Treatment Da (n = 8) Day 1 Day 7 Day 1 Day 7 Day 1 Day 7 Day 1 Day 7 Cmax (ng/mL)b 2.4 (43.6)d 2.8 (6.6)e 3.6 (60.1)f 4.0 (56.3)g 4.8 (20.9)f 4.2 (43.1) 6.6 (31.9)h 6.7 (42.6)g tmax (h)c 3.2 (0.0–4.3)d 1.6 (1.3–2.0)e 2.3 (2.0–4.5)f 2.3 (2.0–4.3)g 4.3 (4.2–4.4)f 4.3 (2.3–4.3) 3.4 (2–12.3)h 2.3 (2.3–8.3)g AUC0–t (ng*h/mL
    • Cmax · full text, Section 'Results':After a single dose on day 1, the maximum observed plasma concentration (Cmax) for CBC increased by 1.3- and 1.8-fold with each twofold increase in dose between Treatments A and B, and Treatments B and D; the median time to peak plasma concentration (tmax) ranged 2.3–4.3 h across treatments.
    • Cmax · full text, Section 'Results':AUC0–12 area under the plasma concentration–time curve from 0- to 12-h time point, AUC0–t area under the plasma concentration–time curve from 0 to the last quantifiable concentration, AUC0–inf area under the plasma concentration–time curve from 0 to infinity, CL/F oral clearance of drug from plasma, Cmax maximum observed plasma concentration, NE not estimable, tmax time to reach CmaxaTreatment A:
    • Tmax · full text, Table 2:Day 7 Day 1 Day 7 Day 1 Day 7 Day 1 Day 7 Cmax (ng/mL)b 2.4 (43.6)d 2.8 (6.6)e 3.6 (60.1)f 4.0 (56.3)g 4.8 (20.9)f 4.2 (43.1) 6.6 (31.9)h 6.7 (42.6)g tmax (h)c 3.2 (0.0–4.3)d 1.6 (1.3–2.0)e 2.3 (2.0–4.5)f 2.3 (2.0–4.3)g 4.3 (4.2–4.4)f 4.3 (2.3–4.3) 3.4 (2–12.3)h 2.3 (2.3–8.3)g AUC0–t (ng*h/mL)b 2.2 (75.2)i 2.3 (35.0)e 5.6 (83.9)f 5.9 (74.1)g 9.0 (41.4)f 9.9 (47.3) 17.6 (37.4)h 26.8 (31.6)g AUC0–12
    • Tmax · full text, Section 'Results':After a single dose on day 1, the maximum observed plasma concentration (Cmax) for CBC increased by 1.3- and 1.8-fold with each twofold increase in dose between Treatments A and B, and Treatments B and D; the median time to peak plasma concentration (tmax) ranged 2.3–4.3 h across treatments.
    • Tmax · full text, Section 'Results':AUC0–12 area under the plasma concentration–time curve from 0- to 12-h time point, AUC0–t area under the plasma concentration–time curve from 0 to the last quantifiable concentration, AUC0–inf area under the plasma concentration–time curve from 0 to infinity, CL/F oral clearance of drug from plasma, Cmax maximum observed plasma concentration, NE not estimable, tmax time to reach CmaxaTreatment A:
    • AUC · full text, Table 2:6 (31.9)h 6.7 (42.6)g tmax (h)c 3.2 (0.0–4.3)d 1.6 (1.3–2.0)e 2.3 (2.0–4.5)f 2.3 (2.0–4.3)g 4.3 (4.2–4.4)f 4.3 (2.3–4.3) 3.4 (2–12.3)h 2.3 (2.3–8.3)g AUC0–t (ng*h/mL)b 2.2 (75.2)i 2.3 (35.0)e 5.6 (83.9)f 5.9 (74.1)g 9.0 (41.4)f 9.9 (47.3) 17.6 (37.4)h 26.8 (31.6)g AUC0–12 (h*ng/mL)b - 5.7 (3.4)e - 9.0 (46.3)g - 13.6 (34.5) - 29.5 (26.5)g AUC0–inf (h*ng/mL)b NE NE NE NE NE 44.2 (6.9)e NE 107.8 (-)j
    • AUC · full text, Section 'Results':Thus, steady-state concentration of CBC could not be calculated.Table 2Plasma pharmacokinetic parameters for cannabichromene (CBC)Pharmacokinetic parameter (unit)Treatment Aa (n = 8)Treatment Ba (n = 8)Treatment Ca (n = 8)Treatment Da (n = 8)Day 1Day 7Day 1Day 7Day 1Day 7Day 1Day 7Cmax (ng/mL)b2.4 (43.6)d2.8 (6.6)e3.6 (60.1)f4.0 (56.3)g4.8 (20.9)f4.2 (43.1)6.6 (31.9)h6.7 (42.6)gtmax (h)c3.2 (0.0–4
    • AUC · full text, Section 'Results':AUC0–12 area under the plasma concentration–time curve from 0- to 12-h time point, AUC0–t area under the plasma concentration–time curve from 0 to the last quantifiable concentration, AUC0–inf area under the plasma concentration–time curve from 0 to infinity, CL/F oral clearance of drug from plasma, Cmax maximum observed plasma concentration, NE not estimable, tmax time to reach CmaxaTreatment A:
    • Relative bioavailability · full text, Section 'Results':After a single dose on day 1, the maximum observed plasma concentration (Cmax) for CBC increased by 1.3- and 1.8-fold with each twofold increase in dose between Treatments A and B, and Treatments B and D; the median time to peak plasma concentration (tmax) ranged 2.3–4.3 h across treatments.
    • Relative bioavailability · full text, Section 'Results':Moderate accumulation was noted on day 7 after a week of twice-daily dosing of Spectrum Yellow oil, with the Cmax increasing by 1.4- and 1.7-fold, and the area under the curve from time 0 to 12 h (AUC0–12) increasing by 1.6- and 3.3-fold with each twofold increase in dose of CBC between Treatments A and B, and Treatments B and D.
    • Relative bioavailability · full text, Section 'Results':On Days 1 and 7, while the dose of CBD was 18 times higher than that of CBC, the area under the curve from time 0 to last measurable concentration (AUC0–t) of CBD was only 6.6–9.8 fold higher than that of CBC (in Treatment D, where CBC was quantifiable in most samples); the dose of THC was similar to the dose of CBC, yet THC was quantifiable in fewer plasma samples than CBC.
42. HumanCannabidiol and Cannabidiol Metabolites: Pharmacokinetics, Interaction with Food, and Influence on Liver Function.
    Nutrients, 2022 · Design: randomized; crossover · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 35631293DOI 10.3390/nu14102152PMC9144241 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Cmax · full text, Section '3.4. Influence of Food on the CBD Pharma':Ingestion of CBD with prior consumption of food increased tmax from 38.2 ± 24.9 to 113.6 ± 70.5 min (p = 0.002), increased Cmax from 1.8 ± 1.5 to 2.9 ± 1.3 ng/mL (p = 0.045), and increased AUC0–4 from 177 ± 104 to 397 ± 167 min × ng/mL (p < 0.001).
    • Tmax · full text, Section '3.4. Influence of Food on the CBD Pharma':Ingestion of CBD with prior consumption of food increased tmax from 38.2 ± 24.9 to 113.6 ± 70.5 min (p = 0.002), increased Cmax from 1.8 ± 1.5 to 2.9 ± 1.3 ng/mL (p = 0.045), and increased AUC0–4 from 177 ± 104 to 397 ± 167 min × ng/mL (p < 0.001).
    • AUC · full text, Section '3.4. Influence of Food on the CBD Pharma':Ingestion of CBD with prior consumption of food increased tmax from 38.2 ± 24.9 to 113.6 ± 70.5 min (p = 0.002), increased Cmax from 1.8 ± 1.5 to 2.9 ± 1.3 ng/mL (p = 0.045), and increased AUC0–4 from 177 ± 104 to 397 ± 167 min × ng/mL (p < 0.001).
43. HumanPharmacokinetic Profile of ∆9-Tetrahydrocannabinol, Cannabidiol and Metabolites in Blood following Vaporization and Oral Ingestion of Cannabidiol Products.
    J Anal Toxicol, 2022 · Design: randomized; double-blind · n: n = 18 · abstract only (PubMed) · not checked (off-topic)
    PMID 35438179DOI 10.1093/jat/bkab124PMC9282269 (free full text)
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:The mean Cmax and range of CBD blood concentrations for each product were as follows: vaporized CBD-dominant cannabis, 171.1 ng/mL, 40.0-665.0 ng/mL, vaporized CBD 104.6 ng/mL, 19.0-312.0 ng/mL and oral CBD, 13.7 ng/mL, 0.0-50.0 ng/mL.
    • Cmax · abstract:The mean Cmax and range of CBD blood concentrations for each product were as follows: vaporized CBD-dominant cannabis, 171.1 ng/mL, 40.0-665.0 ng/mL, vaporized CBD 104.6 ng/mL, 19.0-312.0 ng/mL and oral CBD, 13.7 ng/mL, 0.0-50.0 ng/mL.
    • Food effect · abstract:An optional fifth experimental condition was completed for six participants in which they fasted from all food for 12 h prior to oral ingestion of 100 mg of CBD.
44. HumanPilot clinical and pharmacokinetic study of Δ9-Tetrahydrocannabinol (THC)/Cannabidiol (CBD) nanoparticle oro-buccal spray in patients with advanced cancer experiencing uncontrolled pain.
    PLoS One, 2022 · Design: not stated · n: n = 5 · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 36240167DOI 10.1371/journal.pone.0270543PMC9565400 (free full text)PDF
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:Stage I was a single escalating dose (n = 5) [2.5 mg Δ9-THC and 2.5 mg CBD) versus a 3-fold escalated dose.
    • Key findings · abstract:The water-soluble formulation in the current study resulted in a higher median (min, max) systemic exposure of Δ9-THC than CBD (AUC from 2.5 mg each of Δ9-THC and CBD, was 1.71 ng mL.h-1 (1.1, 6.6) and 0.65 ng mL.h-1 (0.49, 4.1), respectively).
    • Key findings · abstract:The water-soluble cannabis-based medicine provided acceptable bioavailability for Δ9-THC/CBD, appeared safe and tolerable in advanced incurable cancers with uncontrolled pain with preliminary evidence of analgesic efficacy.
    • AUC · abstract:The water-soluble formulation in the current study resulted in a higher median (min, max) systemic exposure of Δ9-THC than CBD (AUC from 2.5 mg each of Δ9-THC and CBD, was 1.71 ng mL.h-1 (1.1, 6.6) and 0.65 ng mL.h-1 (0.49, 4.1), respectively).
    • Relative bioavailability · abstract:Stage I was a single escalating dose (n = 5) [2.5 mg Δ9-THC and 2.5 mg CBD) versus a 3-fold escalated dose.
    • Cmax · full text, Table 4:g CBDMedian (Min, Max) Day 2 (n = 5)7.5 mg Δ9-THC+ 7.5 mg CBDMedian (Min, Max) Δ9THC ⊥ AUC(0-t) ng mL.h−1 1.71 (1.11, 6.61)* 8.26 (2.67, 11.72) Cmax ng mL−1 1.31 (0.76, 2.94)* 2.35 (1.09, 3.19) tmax hours 0.75 (0.5, 1.5)* 1.00 (0.5, 2.0) t1/2 hours 0.94 (0.75, 1.14)* 1.39 (1.30, 2.88) CBD AUC(0-t) ng mL.h−1 0.65 (0.49, 4.06)* 5.96 (1.51, 12.15)* Cmax ng mL−1 0.58 (0.48, 2.45)* 1.55 (0.62
    • Cmax · full text, Section 'Pharmacokinetic parameters':For the 2.5 mg Δ9-THC/2.5 mg CBD dose, the median Cmax of Δ9-THC was 1.31 ng/mL, 2.3-fold higher than the 0.58 ng/mL for CBD; and the median AUC(0-t) of Δ9-THC was 1.71 hr.ng/mL, 2.5-fold higher than the 0.65 hr.ng/mL for CBD (Table 3).
    • Tmax · full text, Table 4:7.5 mg CBDMedian (Min, Max) Δ9THC ⊥ AUC(0-t) ng mL.h−1 1.71 (1.11, 6.61)* 8.26 (2.67, 11.72) Cmax ng mL−1 1.31 (0.76, 2.94)* 2.35 (1.09, 3.19) tmax hours 0.75 (0.5, 1.5)* 1.00 (0.5, 2.0) t1/2 hours 0.94 (0.75, 1.14)* 1.39 (1.30, 2.88) CBD AUC(0-t) ng mL.h−1 0.65 (0.49, 4.06)* 5.96 (1.51, 12.15)* Cmax ng mL−1 0.58 (0.48, 2.45)* 1.55 (0.62, 2.25) tmax hours 0.75 (0.5, 1.5)* 1.00 (0.5, 2.0)
    • Tmax · full text, Section 'Pharmacokinetic parameters':There was a rapid uptake of Δ9-THC and CBD, as indicated by detectable plasma concentrations at the first 30 minute time point following oro-buccal administration (Fig 2) and cannabinoids having a median tmax of 0.75 hours (Table 3).
    • AUC · full text, Table 4:c parameters. Parameter Day 1 (n = 5)2.5 mg Δ9-THC+ 2.5 mg CBDMedian (Min, Max) Day 2 (n = 5)7.5 mg Δ9-THC+ 7.5 mg CBDMedian (Min, Max) Δ9THC ⊥ AUC(0-t) ng mL.h−1 1.71 (1.11, 6.61)* 8.26 (2.67, 11.72) Cmax ng mL−1 1.31 (0.76, 2.94)* 2.35 (1.09, 3.19) tmax hours 0.75 (0.5, 1.5)* 1.00 (0.5, 2.0) t1/2 hours 0.94 (0.75, 1.14)* 1.39 (1.30, 2.88) CBD AUC(0-t) ng mL.h−1 0.65 (0.49, 4.06)* 5.96
    • AUC · full text, Section 'Pharmacokinetic parameters':For the 2.5 mg Δ9-THC/2.5 mg CBD dose, the median Cmax of Δ9-THC was 1.31 ng/mL, 2.3-fold higher than the 0.58 ng/mL for CBD; and the median AUC(0-t) of Δ9-THC was 1.71 hr.ng/mL, 2.5-fold higher than the 0.65 hr.ng/mL for CBD (Table 3).
    • Relative bioavailability · full text, Section 'Inclusion and exclusion criteria':Patients were excluded from participation if they met any of the following: i) demonstrated cognitive impairment or intellectual disability; ii) had a history of primary psychotic disorder, bipolar affective disorder, bipolar disorder with psychotic features, depressive disorder with psychotic features, borderline personality disorder, antisocial personality disorder, or a positive family history
    • Relative bioavailability · full text, Section 'Pharmacokinetic parameters':For the 2.5 mg Δ9-THC/2.5 mg CBD dose, the median Cmax of Δ9-THC was 1.31 ng/mL, 2.3-fold higher than the 0.58 ng/mL for CBD; and the median AUC(0-t) of Δ9-THC was 1.71 hr.ng/mL, 2.5-fold higher than the 0.65 hr.ng/mL for CBD (Table 3).
    • Form comparison · full text, Section 'Pharmacokinetic parameters':The PK assessment of a single dose of 2.5 mg each of THC and CBD (2 sprays on Day 1) versus 7.5 mg each of Δ9-THC and CBD (six sprays on Day 2) was investigated for all participants in Stage I.
45. HumanUrinary Pharmacokinetic Profile of Cannabidiol (CBD), Δ9-Tetrahydrocannabinol (THC) and Their Metabolites following Oral and Vaporized CBD and Vaporized CBD-Dominant Cannabis Administration.
    J Anal Toxicol, 2022 · Design: not stated · n: n = 18 · abstract only (PubMed) · not checked (off-topic)
    PMID 34089060DOI 10.1093/jat/bkab059PMC9122505 (free full text)
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:This study characterized the urinary pharmacokinetics of CBD (100 mg) following vaporization or oral administration (including three formulations: gelcap, pharmacy-grade syrup and or Epidiolex) as well as vaporized CBD-dominant cannabis (containing 100 mg CBD and 3.7 mg Δ9-THC) in healthy adults (n = 18).
    • Key findings · abstract:Urinary CBD concentrations (ng/mL) were higher after oral (mean Cmax: 734; mean Tmax: 4.7 h, n = 18) versus vaporized CBD (mean Cmax: 240; mean Tmax: 1.3 h, n = 18), and oral dose formulation significantly impacted mean Cmax (Epidiolex = 1,274 ng/mL, capsule = 776 ng/mL, syrup = 151 ng/mL,[excerpt truncated in our database — see source]
    • Cmax · abstract:Urinary CBD concentrations (ng/mL) were higher after oral (mean Cmax: 734; mean Tmax: 4.7 h, n = 18) versus vaporized CBD (mean Cmax: 240; mean Tmax: 1.3 h, n = 18), and oral dose formulation significantly impacted mean Cmax (Epidiolex = 1,274 ng/mL, capsule = 776 ng/mL, syrup = 151 ng/mL, n = 6/group) with little difference in Tmax.
    • Tmax · abstract:Urinary CBD concentrations (ng/mL) were higher after oral (mean Cmax: 734; mean Tmax: 4.7 h, n = 18) versus vaporized CBD (mean Cmax: 240; mean Tmax: 1.3 h, n = 18), and oral dose formulation significantly impacted mean Cmax (Epidiolex = 1,274 ng/mL, capsule = 776 ng/mL, syrup = 151 ng/mL, n = 6/group) with little difference in Tmax.
    • Food effect · abstract:A subset of participants (n = 6) orally administered CBD syrup following overnight fasting (versus low-fat breakfast).
    • Food effect · abstract:Overnight fasting had limited impact on CBD excretion in urine, and there was no evidence of CBD conversion to Δ8- or Δ9-THC in any route or formulation in which pure CBD was administered.
46. HumanPharmacokinetics of Cannabidiol in the Hispaniolan Amazon Parrot (Amazona ventralis).
    J Avian Med Surg, 2022 · Design: not stated · abstract only (PubMed) · open access (green)
    PMID 35972864DOI 10.1647/20-00076
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Because the maximum serum concentrations (Cmax) for these doses were 5.5 and 13 ng/mL, respectively, and the serum half-life was 2 hours for both groups, the doses were considered too low for clinical use in this species.
    • Key findings · abstract:The areas under the curve (h·ng/mL) were 518 and 1863, Cmax (ng/ mL) were 213 and 562, and times to achieve Cmax (hours) were 0.5 and 4 for the 60 and 120 mg/kg doses, respectively.
    • Key findings · abstract:The serum half-life could not be determined in the 60 mg/kg treatment, but was 1.28 hours at 120 mg/kg.
    • Cmax · abstract:Because the maximum serum concentrations (Cmax) for these doses were 5.5 and 13 ng/mL, respectively, and the serum half-life was 2 hours for both groups, the doses were considered too low for clinical use in this species.
    • Cmax · abstract:The areas under the curve (h·ng/mL) were 518 and 1863, Cmax (ng/ mL) were 213 and 562, and times to achieve Cmax (hours) were 0.5 and 4 for the 60 and 120 mg/kg doses, respectively.
47. HumanEffect of two oral formulations of cannabidiol on responses to emotional stimuli in healthy human volunteers: pharmaceutical vehicle matters.
    Braz J Psychiatry, 2022 · Design: randomized; double-blind · n: 15 subjects · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 34076067DOI 10.1590/1516-4446-2020-1684PMC8827362 (free full text)PDF
    Verification: full text read; no PK numbers matched
48. HumanIn vitro percutaneous absorption studies of cannabidiol using human skin: Exploring the effect of drug concentration, chemical enhancers, and essential oils.
    Int J Pharm, 2022 · Design: not stated · abstract only (PubMed) · closed/paywalled
    PMID 35124116DOI 10.1016/j.ijpharm.2022.121540
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:The 24 h study results suggest no significant difference in amount of drug absorbed into skin, between 5% (242.41 ± 12.17 µg/cm2) and 10% (232.79 ± 20.82 cm2) cannabidiol solutions.
    • Key findings · abstract:Oleic acid (43.07 ± 10.11 µg/cm2) had significantly higher cannabidiol delivery into skin than the group without oleic acid (10.98 ± 3.40 µg/cm2) after a 4 h in vitro permeation study.
    • Fractional absorption · abstract:The 24 h study results suggest no significant difference in amount of drug absorbed into skin, between 5% (242.41 ± 12.17 µg/cm2) and 10% (232.79 ± 20.82 cm2) cannabidiol solutions.
49. HumanA phase I trial of the safety, tolerability and pharmacokinetics of cannabidiol administered as single-dose oil solution and single and multiple doses of a sublingual wafer in healthy volunteers.
    Br J Clin Pharmacol, 2021 · Design: randomized; crossover · n: 12 healthy volunteers · abstract only (PubMed) · open access (bronze)
    PMID 33075170DOI 10.1111/bcp.14617
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:The relative bioavailability of CBD after administration as a sublingual wafer was comparable with that of oil solution with 90% confidence interval of 83-131%.
    • Key findings · abstract:There was no statistically significant difference between the AUC0-τ of CBD after administration of oil solution or wafer compared with nabiximols oromucosal spray.
    • AUC · abstract:There was no statistically significant difference between the AUC0-τ of CBD after administration of oil solution or wafer compared with nabiximols oromucosal spray.
    • Relative bioavailability · abstract:The relative bioavailability of CBD after administration as a sublingual wafer was comparable with that of oil solution with 90% confidence interval of 83-131%.
50. HumanImproved Bioavailability with Dry Powder Cannabidiol Inhalation: A Phase 1 Clinical Study.
    J Pharm Sci, 2021 · Design: not stated · n: n=10 · abstract only (PubMed) · open access (hybrid)
    PMID 34400185DOI 10.1016/j.xphs.2021.08.012
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Following oral administration, the inactive metabolite blood concentration is ∼40-fold higher than CBD.
    • Key findings · abstract:Following a single dose of Epidiolex or DPI CBD (n=10 PK evaluable participants each), the maximum CBD concentration for the inhaled powder was 71-fold higher than that of Epidiolex while administering 24-fold less CBD.
    • Relative bioavailability · abstract:Following oral administration, the inactive metabolite blood concentration is ∼40-fold higher than CBD.
    • Relative bioavailability · abstract:Following a single dose of Epidiolex or DPI CBD (n=10 PK evaluable participants each), the maximum CBD concentration for the inhaled powder was 71-fold higher than that of Epidiolex while administering 24-fold less CBD.
51. HumanComparison of Five Oral Cannabidiol Preparations in Adult Humans: Pharmacokinetics, Body Composition, and Heart Rate Variability.
    Pharmaceuticals (Basel), 2021 · Design: randomized; crossover · n: 15 healthy men · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 33418866DOI 10.3390/ph14010035PMC7825058 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Tmax · abstract:Peak circulating CBD concentration, time to peak concentration, and area under the curve was superior in a preparation comprising 5% CBD concentration liquid.
    • Tmax · abstract:Fat free mass was a significant predictor (R 2 = 0.365, p = 0.017) of time to peak concentration for this preparation.
    • AUC · abstract:Peak circulating CBD concentration, time to peak concentration, and area under the curve was superior in a preparation comprising 5% CBD concentration liquid.
    • Cmax · full text, Table 6:s of current preparations with previously reported studies of ingestible cannabidiol. Study Formulation, Administration, CBD Single Dose (mg) Tmax(h) Cmax(ng/mL) AUC0-t(h × ng/mL) AUC0-inf(h × ng/mL) t½(h) Ka(1/h) Ke(1/h) Vd(L) [26] Oral capsule (CBD + THC) 5.4 mg 0.99 0.93 4.35 [27] Oral capsule (CBD + THC) 5.4 mg 1.0 0.95 [28] GW oral capsule (CBD + THC) 10 mg 1.27 2.47 5.7
    • Tmax · full text, Table 6:arameters of current preparations with previously reported studies of ingestible cannabidiol. Study Formulation, Administration, CBD Single Dose (mg) Tmax(h) Cmax(ng/mL) AUC0-t(h × ng/mL) AUC0-inf(h × ng/mL) t½(h) Ka(1/h) Ke(1/h) Vd(L) [26] Oral capsule (CBD + THC) 5.4 mg 0.99 0.93 4.35 [27] Oral capsule (CBD + THC) 5.4 mg 1.0 0.95 [28] GW oral capsule (CBD + THC) 10 mg 1.27
    • AUC · full text, Table 6:preparations with previously reported studies of ingestible cannabidiol. Study Formulation, Administration, CBD Single Dose (mg) Tmax(h) Cmax(ng/mL) AUC0-t(h × ng/mL) AUC0-inf(h × ng/mL) t½(h) Ka(1/h) Ke(1/h) Vd(L) [26] Oral capsule (CBD + THC) 5.4 mg 0.99 0.93 4.35 [27] Oral capsule (CBD + THC) 5.4 mg 1.0 0.95 [28] GW oral capsule (CBD + THC) 10 mg 1.27 2.47 5.76 6.03 1.09
    • AUC · full text, Section '2.2. Circulating CBD and Pharmacokinetic':It was not possible to calculate some pharmacokinetic parameters (i.e., AUCinf, t½, Ke and Vd) for all of the CBD preparations on account of insufficient values above the limit of quantitation during the initial 1–2 h of blood collection.
52. HumanA pilot safety, tolerability and pharmacokinetic study of an oro-buccal administered cannabidiol-dominant anti-inflammatory formulation in healthy individuals: a randomized placebo-controlled single-blinded study.
    Inflammopharmacology, 2021 · Design: randomized · n: 12 participants · abstract only (PubMed) · closed/paywalled
    PMID 34357480DOI 10.1007/s10787-021-00859-y
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Bioavailability of a 6 mg and 18 mg dose of CBD (median IQR) was 0.87 and 8.9 ng h mL-1, respectively.
53. HumanPharmacokinetics of cannabidiol in children with refractory epileptic encephalopathy.
    Epilepsia, 2021 · Design: not stated · abstract only (PubMed) · closed/paywalled
    PMID 33280111DOI 10.1111/epi.16781
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Median (range) CBD time to maximum plasma concentration, maximum plasma concentration, and area under the concentration versus time curve up to 6 hours after dosing were 3.2 hours (1.9-6.2), 49.6 ng/mL (14.4-302.0), and 226.3 ng ⋅ h/mL (70.5-861.3), respectively.
    • Key findings · abstract:Most of our patients (83%) showed little CBD plasma level fluctuation during a dosing interval, comparable to that encountered after oral administration of an extended release drug delivery system.
    • AUC · abstract:Median (range) CBD time to maximum plasma concentration, maximum plasma concentration, and area under the concentration versus time curve up to 6 hours after dosing were 3.2 hours (1.9-6.2), 49.6 ng/mL (14.4-302.0), and 226.3 ng ⋅ h/mL (70.5-861.3), respectively.
54. HumanPharmacokinetic investigation of synthetic cannabidiol oral formulations in healthy volunteers.
    Eur J Pharm Biopharm, 2020 · Design: crossover · abstract only (PubMed) · closed/paywalled
    PMID 32634571DOI 10.1016/j.ejpb.2020.06.021
    Verification: abstract-only auto-extract; unverified
55. HumanEvaluation of pharmacokinetics and acute anti-inflammatory potential of two oral cannabidiol preparations in healthy adults.
    Phytother Res, 2020 · Design: randomized; double-blind · n: 10 healthy adults · abstract only (PubMed) · closed/paywalled
    PMID 32147925DOI 10.1002/ptr.6651
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:The water-soluble powder had Cmax = 2.82 ng/ml, Tmax = 90 min, and was approximately ×4.5 more bioavailable than the lipid-soluble form.
    • Cmax · abstract:The water-soluble powder had Cmax = 2.82 ng/ml, Tmax = 90 min, and was approximately ×4.5 more bioavailable than the lipid-soluble form.
    • Tmax · abstract:The water-soluble powder had Cmax = 2.82 ng/ml, Tmax = 90 min, and was approximately ×4.5 more bioavailable than the lipid-soluble form.
56. HumanA phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects.
    Epilepsia, 2020 · Design: randomized · n: n = 15 · full text (Europe PMC XML) + abstract · open access (hybrid)
    PMID 32012251DOI 10.1111/epi.16419PMC7065230 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:PK parameters (maximum observed plasma concentration [Cmax ], area under the plasma concentration-time curve from time zero to the last observed quantifiable concentration, area under the concentration-time curve from time zero to infinity [AUC0-∞ ], and time to maximum plasma concentration [tmax ]) of CBD and its major metabolites were derived using noncompartmental analysis.
    • Key findings · abstract:RESULTS: CBD exposure increased by 3.8-fold for AUC0-∞ and 5.2-fold for Cmax when CBD was administered with a high-fat/calorie meal versus fasted.
    • Key findings · abstract:To a lesser extent, a low-fat/calorie meal enhanced CBD exposure vers[excerpt truncated in our database — see source]
    • Cmax · abstract:PK parameters (maximum observed plasma concentration [Cmax ], area under the plasma concentration-time curve from time zero to the last observed quantifiable concentration, area under the concentration-time curve from time zero to infinity [AUC0-∞ ], and time to maximum plasma concentration [tmax ]) of CBD and its major metabolites were derived using noncompartmental analysis.
    • Cmax · abstract:RESULTS: CBD exposure increased by 3.8-fold for AUC0-∞ and 5.2-fold for Cmax when CBD was administered with a high-fat/calorie meal versus fasted.
    • Cmax · abstract:To a lesser extent, a low-fat/calorie meal enhanced CBD exposure vers
    • Tmax · abstract:PK parameters (maximum observed plasma concentration [Cmax ], area under the plasma concentration-time curve from time zero to the last observed quantifiable concentration, area under the concentration-time curve from time zero to infinity [AUC0-∞ ], and time to maximum plasma concentration [tmax ]) of CBD and its major metabolites were derived using noncompartmental analysis.
    • Tmax · abstract:The same trend was seen for the CBD metabolites, except that 7-carboxy-cannabidiol tmax was considerably longer when CBD was administered with alcohol (14 vs 4 hours fasted).
    • AUC · abstract:PK parameters (maximum observed plasma concentration [Cmax ], area under the plasma concentration-time curve from time zero to the last observed quantifiable concentration, area under the concentration-time curve from time zero to infinity [AUC0-∞ ], and time to maximum plasma concentration [tmax ]) of CBD and its major metabolites were derived using noncompartmental analysis.
    • AUC · abstract:RESULTS: CBD exposure increased by 3.8-fold for AUC0-∞ and 5.2-fold for Cmax when CBD was administered with a high-fat/calorie meal versus fasted.
    • AUC · abstract:To a lesser extent, a low-fat/calorie meal enhanced CBD exposure vers
    • Relative bioavailability · abstract:RESULTS: CBD exposure increased by 3.8-fold for AUC0-∞ and 5.2-fold for Cmax when CBD was administered with a high-fat/calorie meal versus fasted.
    • Relative bioavailability · abstract:To a lesser extent, a low-fat/calorie meal enhanced CBD exposure versus fasted with a 2.7-fold increase in AUC0-∞ and a 3.8-fold increase in Cmax .
    • Relative bioavailability · abstract:Similarly, when dosed with whole milk, CBD exposure increased versus fasted by 2.4-fold for AUC0-∞ and 3.1-fold for Cmax .
    • Relative bioavailability · abstract:Modest elevations in CBD exposure occurred when it was dosed with alcohol: 1.6-fold for AUC0-∞ and 1.9-fold for Cmax .
    • Food effect · abstract:Epidiolex in the USA and Epidyolex in Europe; 100-mg/mL oral solution) were assessed in healthy adults following a high-fat/calorie meal (n = 15), a low-fat/calorie meal (n = 14), whole milk (n = 15), or alcohol (n = 14), relative to the fasted state (n = 29).
    • Food effect · abstract:RESULTS: CBD exposure increased by 3.8-fold for AUC0-∞ and 5.2-fold for Cmax when CBD was administered with a high-fat/calorie meal versus fasted.
    • Food effect · abstract:To a lesser extent, a low-fat/calorie meal enhanced CBD exposure versus fasted with a 2.7-fold increase in AUC0-∞ and a 3.8-fold increase in Cmax .
    • Food effect · abstract:Similarly, when dosed with whole milk,
    • Cmax · full text, Table 3:ow‐fat/calorie), whole milk, or alcohol; PK analysis set Comparison Ratio of geometric least squares means (90% CI) AUC0‐t,a h·ng/mL AUC0‐∞,a h·ng/mL Cmax,a ng/mL tmax,b h CBD High‐fat/calorie vs fasted 3.99 (3.37, 4.73) 3.84 (3.24, 4.55) 5.22 (4.25, 6.41) −0.50 (−1.00, 0.50) Low‐fat/calorie vs fasted 2.86 (2.41, 3.40) 2.72 (2.29, 3.24) 3.76 (3.05, 4.63) 0.54 (0.00, 1.50) Whole milk vs fasted 2.47
    • Cmax · full text, Section 'CBD exposure':In all cases, the 90% CI for AUC0‐t, AUC0‐∞, and Cmax of CBD did not include 1 (Tables 2 and 3, and Figure 2).
    • Cmax · full text, Section '7‐OH‐CBD exposure':In all cases, the 90% CI for AUC0‐t, AUC0‐∞, and Cmax did not include 1 (Tables 2 and 3, and Figure 2).
    • Tmax · full text, Table 3:e), whole milk, or alcohol; PK analysis set Comparison Ratio of geometric least squares means (90% CI) AUC0‐t,a h·ng/mL AUC0‐∞,a h·ng/mL Cmax,a ng/mL tmax,b h CBD High‐fat/calorie vs fasted 3.99 (3.37, 4.73) 3.84 (3.24, 4.55) 5.22 (4.25, 6.41) −0.50 (−1.00, 0.50) Low‐fat/calorie vs fasted 2.86 (2.41, 3.40) 2.72 (2.29, 3.24) 3.76 (3.05, 4.63) 0.54 (0.00, 1.50) Whole milk vs fasted 2.47 (2.08, 2.92)
    • AUC · full text, Table 3:meal types (high‐fat/calorie or low‐fat/calorie), whole milk, or alcohol; PK analysis set Comparison Ratio of geometric least squares means (90% CI) AUC0‐t,a h·ng/mL AUC0‐∞,a h·ng/mL Cmax,a ng/mL tmax,b h CBD High‐fat/calorie vs fasted 3.99 (3.37, 4.73) 3.84 (3.24, 4.55) 5.22 (4.25, 6.41) −0.50 (−1.00, 0.50) Low‐fat/calorie vs fasted 2.86 (2.41, 3.40) 2.72 (2.29, 3.24) 3.76 (3.05, 4.63) 0.54 (0.00
    • AUC · full text, Section 'CBD exposure':In all cases, the 90% CI for AUC0‐t, AUC0‐∞, and Cmax of CBD did not include 1 (Tables 2 and 3, and Figure 2).
    • AUC · full text, Section '7‐OH‐CBD exposure':In all cases, the 90% CI for AUC0‐t, AUC0‐∞, and Cmax did not include 1 (Tables 2 and 3, and Figure 2).
    • Food effect · full text, Table 3:Statistical analysis of PK parameters following administration of 750‐mg CBD under fasted conditions compared with various meal types (high‐fat/calorie or low‐fat/calorie), whole milk, or alcohol; PK analysis set Comparison Ratio of geometric least squares means (90% CI) AUC0‐t,a h·ng/mL AUC0‐∞,a h·ng/mL Cmax,a ng/mL tmax,b h CBD High‐fa
    • Food effect · full text, Section 'Safety':In the fasted group, 14 (48%) subjects experienced at least one AE versus six (40%) in the high‐fat/calorie group, eight (57%) in the low‐fat/calorie group, eight (53%) in the whole milk group, and 12 (80%) in the alcohol group.
    • Form comparison · full text, Table 3:Statistical analysis of PK parameters following administration of 750‐mg CBD under fasted conditions compared with various meal types (high‐fat/calorie or low‐fat/calorie), whole milk, or alcohol; PK analysis set Comparison Ratio of geometric least squares means (90% CI) AUC0‐t,a h·ng/mL AUC0‐∞,a h·ng/mL Cmax,a ng/mL tmax,b h CBD High‐fat/calorie vs fasted 3.99
    • Form comparison · full text, Section 'Safety':In the fasted group, 14 (48%) subjects experienced at least one AE versus six (40%) in the high‐fat/calorie group, eight (57%) in the low‐fat/calorie group, eight (53%) in the whole milk group, and 12 (80%) in the alcohol group.
    • Form comparison · full text, Section 'Safety':More subjects were affected by headache while taking CBD with alcohol (eight [53%] subjects) versus the other treatment groups (7%‐21% subjects affected).
57. HumanUrinary Pharmacokinetic Profile of Cannabinoids Following Administration of Vaporized and Oral Cannabidiol and Vaporized CBD-Dominant Cannabis.
    J Anal Toxicol, 2020 · Design: crossover · n: n = 6 · abstract only (PubMed) · not checked (off-topic)
    PMID 31682266DOI 10.1093/jat/bkz080PMC7152694 (free full text)
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:This study characterized the urinary pharmacokinetic profile of 100-mg oral and vaporized CBD, vaporized CBD-dominant cannabis (100-mg CBD; 3.7-mg ∆9-THC) and placebo in healthy adults (n = 6) using a within-subjects crossover design.
    • Key findings · abstract:Urinary concentrations of CBD were higher after oral (mean Cmax: 776 ng/mL) versus vaporized CBD (mean Cmax: 261 ng/mL).
    • Cmax · abstract:Urinary concentrations of CBD were higher after oral (mean Cmax: 776 ng/mL) versus vaporized CBD (mean Cmax: 261 ng/mL).
58. HumanA Phase I, Open-Label, Parallel-Group, Single-Dose Trial of the Pharmacokinetics, Safety, and Tolerability of Cannabidiol in Subjects with Mild to Severe Renal Impairment.
    Clin Pharmacokinet, 2020 · Design: not stated · n: n = 8 · full text (Europe PMC XML) + abstract · open access (hybrid)
    PMID 31802404DOI 10.1007/s40262-019-00841-6PMC7292807 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:RESULTS: No statistically significant differences were observed in Cmax, AUCt, AUC∞, or tmax values between subjects with mild, moderate, or severe renal impairment and subjects with normal renal function for CBD or its major metabolites, 7-carboxy-CBD (7-COOH-CBD) and 7-hydroxy-CBD (7-OH-CBD), and minor metabolite, 6-hydroxy-CBD (6-OH-CBD); geometric mean ratio for Cmax values ranged from 0.68 to 1.35.
    • Cmax · abstract:RESULTS: No statistically significant differences were observed in Cmax, AUCt, AUC∞, or tmax values between subjects with mild, moderate, or severe renal impairment and subjects with normal renal function for CBD or its major metabolites, 7-carboxy-CBD (7-COOH-CBD) and 7-hydroxy-CBD (7-OH-CBD), and minor metabolite, 6-hydroxy-CBD (6-OH-CBD); geometric mean ratio for Cmax values ranged from 0.68 to 1.35.
    • Tmax · abstract:RESULTS: No statistically significant differences were observed in Cmax, AUCt, AUC∞, or tmax values between subjects with mild, moderate, or severe renal impairment and subjects with normal renal function for CBD or its major metabolites, 7-carboxy-CBD (7-COOH-CBD) and 7-hydroxy-CBD (7-OH-CBD), and minor metabolite, 6-hydroxy-CBD (6-OH-CBD); geometric mean ratio for Cmax values ranged from 0.68 to 1.35.
    • AUC · abstract:RESULTS: No statistically significant differences were observed in Cmax, AUCt, AUC∞, or tmax values between subjects with mild, moderate, or severe renal impairment and subjects with normal renal function for CBD or its major metabolites, 7-carboxy-CBD (7-COOH-CBD) and 7-hydroxy-CBD (7-OH-CBD), and minor metabolite, 6-hydroxy-CBD (6-OH-CBD); geometric mean ratio for Cmax values ranged from 0.68 to 1.35.
    • Cmax · full text, Table:no effect on CBD or its biotransformation products. No statistically significant differences were observed in maximum measured plasma concentration (Cmax), area under the plasma concentration–time curve (AUC) from time zero to last measurable concentration (AUCt), AUC from time zero to infinity (AUC∞), or time to Cmax (tmax) values between subjects with renal impairment and subjects with normal re
    • Cmax · full text, Table 2:d 7-COOH-CBD pharmacokinetic parameters between renal impairment groups and the normal renal function group (pharmacokinetic analysis set) Comparison Cmax [geometric LS mean ratio (90% CI)] AUC∞ [geometric LS mean ratio (90% CI)] AUCt [geometric LS mean ratio (90% CI)] CL/F [geometric LS mean ratio (90% CI)] tmax [difference (90% CI)]a (h) CBD  Mild/normal 1.31 (0.73–2.35) 1.20 (0.59–2.45) 1.44 (0
    • Cmax · full text, Table 3:Pharmacokinetic parameters for cannabidiol, 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD (pharmacokinetic analysis set) Renal function group Cmax (ng/mL)a tmax(h)b t½(h)c,d AUCt (ng·h/mL)a AUC∞ (ng·h/mL)a,d %AUCextraa,e CL/F (L/h)c Vz/F (L)c (n  = 8) (n = 8) (n = 8) (n = 8) (n = 8) (n =  8) (n = 8) (n  = 8) CBD  Mild RI 200 (42.7) 2.5 (1.5–5.0) 15.5f (64.5) 671 (40.9) 600g (50.0) 7.50g (73.0)
    • Tmax · full text, Table:plasma concentration–time curve (AUC) from time zero to last measurable concentration (AUCt), AUC from time zero to infinity (AUC∞), or time to Cmax (tmax) values between subjects with renal impairment and subjects with normal renal function. A single dose of 200 mg CBD was well tolerated across all subject groups, and no safety concerns were observed.
    • Tmax · full text, Table 2:etric LS mean ratio (90% CI)] AUC∞ [geometric LS mean ratio (90% CI)] AUCt [geometric LS mean ratio (90% CI)] CL/F [geometric LS mean ratio (90% CI)] tmax [difference (90% CI)]a (h) CBD  Mild/normal 1.31 (0.73–2.35) 1.20 (0.59–2.45) 1.44 (0.83–2.51) 0.83 (0.41–1.69) 0.25 (0.00–1.00)  Moderate/normal 1.12 (0.62–2.02) 1.05 (0.56–1.96) 1.14 (0.66–1.98) 0.96 (0.51–1.79) 0.00 (− 0.50 to 0.00)  Severe/n
    • Tmax · full text, Table 3:Pharmacokinetic parameters for cannabidiol, 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD (pharmacokinetic analysis set) Renal function group Cmax (ng/mL)a tmax(h)b t½(h)c,d AUCt (ng·h/mL)a AUC∞ (ng·h/mL)a,d %AUCextraa,e CL/F (L/h)c Vz/F (L)c (n  = 8) (n = 8) (n = 8) (n = 8) (n = 8) (n =  8) (n = 8) (n  = 8) CBD  Mild RI 200 (42.7) 2.5 (1.5–5.0) 15.5f (64.5) 671 (40.9) 600g (50.0) 7.50g (73.0) 365g (52.3) 6
    • AUC · full text, Table:ect on CBD or its biotransformation products. No statistically significant differences were observed in maximum measured plasma concentration (Cmax), area under the plasma concentration–time curve (AUC) from time zero to last measurable concentration (AUCt), AUC from time zero to infinity (AUC∞), or time to Cmax (tmax) values between subjects with renal impairment and subjects with normal renal fu
    • AUC · full text, Table 2:between renal impairment groups and the normal renal function group (pharmacokinetic analysis set) Comparison Cmax [geometric LS mean ratio (90% CI)] AUC∞ [geometric LS mean ratio (90% CI)] AUCt [geometric LS mean ratio (90% CI)] CL/F [geometric LS mean ratio (90% CI)] tmax [difference (90% CI)]a (h) CBD  Mild/normal 1.31 (0.73–2.35) 1.20 (0.59–2.45) 1.44 (0.83–2.51) 0.83 (0.41–1.69) 0.25 (0.00–1.
    • AUC · full text, Table 3:ic parameters for cannabidiol, 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD (pharmacokinetic analysis set) Renal function group Cmax (ng/mL)a tmax(h)b t½(h)c,d AUCt (ng·h/mL)a AUC∞ (ng·h/mL)a,d %AUCextraa,e CL/F (L/h)c Vz/F (L)c (n  = 8) (n = 8) (n = 8) (n = 8) (n = 8) (n =  8) (n = 8) (n  = 8) CBD  Mild RI 200 (42.7) 2.5 (1.5–5.0) 15.5f (64.5) 671 (40.9) 600g (50.0) 7.50g (73.0) 365g (52.3) 6661g (55.5)  M
59. HumanA Phase 1, Randomised, Placebo-Controlled, Dose Escalation Study to Investigate the Safety, Tolerability and Pharmacokinetics of Cannabidiol in Fed Healthy Volunteers.
    Eur J Drug Metab Pharmacokinet, 2020 · Design: randomized · full text (Europe PMC XML) + abstract · open access (hybrid)
    PMID 32409982DOI 10.1007/s13318-020-00624-6PMC7511474 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:Blood samples were collected up to 8 days postdose and plasma was analysed by liquid chromatography and mass spectrometry to assess the pharmacokinetics of the CBD formulation.
    • Key findings · abstract:After a high-fat meal, CBD was detected in plasma samples at 15 min postdose; the median time to maximum plasma concentration (Tmax) was 4 h across all three CBD dose cohorts.
    • Key findings · abstract:The CBD plasma exposure [maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC)] increased in a dose-proportional manner and declined to levels approaching the lower level of quantification by day 8.
    • Cmax · abstract:The CBD plasma exposure [maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC)] increased in a dose-proportional manner and declined to levels approaching the lower level of quantification by day 8.
    • Tmax · abstract:After a high-fat meal, CBD was detected in plasma samples at 15 min postdose; the median time to maximum plasma concentration (Tmax) was 4 h across all three CBD dose cohorts.
    • AUC · abstract:The CBD plasma exposure [maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC)] increased in a dose-proportional manner and declined to levels approaching the lower level of quantification by day 8.
    • Food effect · abstract:After a high-fat meal, CBD was detected in plasma samples at 15 min postdose; the median time to maximum plasma concentration (Tmax) was 4 h across all three CBD dose cohorts.
    • Cmax · full text, Table 5:Key pharmacokinetic parameters for the subjects Pharmacokinetic parameters Cmax (ng/mL) Tmax (h) AUClast (h ng/mL) AUCinf (h ng/mL) T1/2 (h) Cohort 1 (5 mg/kg cannabidiol) N 6 6 6 6 6 Mean 296 4.00 1840 1951 70.3  SD 173 2.19 438 441 7.2  CV (%) 58 55 24 23 10  Median 296 4.00 1883 1967 69.4  Minimum 97 2.00 1170 1234 61.6  Max
    • Cmax · full text, Section 'Pharmacokinetic Results':The geometric mean (percent geometric coefficient of variance, GeoCV%) Cmax values were 248 (77%), 626 (57%) and 1,003 ng/mL (55%) for the 5, 10 and 20 mg/kg cannabidiol dose cohorts, respectively.
    • Tmax · full text, Table 5:Key pharmacokinetic parameters for the subjects Pharmacokinetic parameters Cmax (ng/mL) Tmax (h) AUClast (h ng/mL) AUCinf (h ng/mL) T1/2 (h) Cohort 1 (5 mg/kg cannabidiol) N 6 6 6 6 6 Mean 296 4.00 1840 1951 70.3  SD 173 2.19 438 441 7.2  CV (%) 58 55 24 23 10  Median 296 4.00 1883 1967 69.4  Minimum 97 2.00 1170 1234 61.6  Maximum 466 8.00
    • AUC · full text, Table 5:Key pharmacokinetic parameters for the subjects Pharmacokinetic parameters Cmax (ng/mL) Tmax (h) AUClast (h ng/mL) AUCinf (h ng/mL) T1/2 (h) Cohort 1 (5 mg/kg cannabidiol) N 6 6 6 6 6 Mean 296 4.00 1840 1951 70.3  SD 173 2.19 438 441 7.2  CV (%) 58 55 24 23 10  Median 296 4.00 1883 1967 69.4  Minimum 97 2.00 1170 1234 61.6  Maximum 466 8.00 2395 24
    • AUC · full text, Section 'Pharmacokinetic Results':Geometric mean (GeoCV%) AUClast values were 1793 (26%), 4,025 (37%) and 7,618 h ng/mL (28%) for the 5, 10 and 20 mg/kg cannabidiol dose cohorts, respectively.
    • AUC · full text, Section 'Pharmacokinetic Results':Geometric mean (GeoCV%) AUCinf values were 1,905 (25%), 4,227 (37%) and 8,008 h ng/mL (29%) for the 5, 10 and 20 mg/kg cannabidiol dose cohorts, respectively (see Table 5).
    • Food effect · full text, Table:al were consistent with data from other studies of purified pharmaceutical-grade cannabidiol, strengthening support for the idea of administering CBD with food to maximize bioavailability. There is potential for a substantial variation in cannabidiol bioavailability between doses if the fat content of the associated meal varies significantly.
    • Form comparison · full text, Section 'Safety and Tolerability':The most frequently reported TEAEs were headache (17%) (cannabidiol group 3/18 versus placebo group 1/6) and diarrhoea (8%) (cannabidiol group 3/18 versus placebo group 0/6).
60. HumanThe Interplay Between Liver First-Pass Effect and Lymphatic Absorption of Cannabidiol and Its Implications for Cannabidiol Oral Formulations.
    Clin Pharmacokinet, 2020 · Design: not stated · abstract only (PubMed) · open access (green)
    PMID 32785853DOI 10.1007/s40262-020-00931-w
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Due to its very high lipophilicity, cannabidiol (CBD) has physicochemical features (e.g. logP = 6.3) consistent with an oral absorption mediated at least in part by transport via the intestinal lymphatic system.
    • Key findings · abstract:In this manuscript, we discuss (1) evidence for CBD undergoing hepatic first-pass liver metabolism and lymphatic absorption to a clinically important extent;[excerpt truncated in our database — see source]
    • Key findings · abstract:(2) the potential interplay between improved oral absorption, diversion of orally absorbed drug to the lymphatic system, and magnitude of presystemic elimination in the liver; and (3) strategies by which innovative chemical an[excerpt truncated in our database — see source]
    • Fractional absorption · abstract:(2) the potential interplay between improved oral absorption, diversion of orally absorbed drug to the lymphatic system, and magnitude of presystemic elimination in the liver; and (3) strategies by which innovative chemical and/or pharmaceutical delivery systems of CBD with improved bioavailability could be developed.
61. HumanOral Cannabidiol Does Not Convert to Δ8-THC or Δ9-THC in Humans: A Pharmacokinetic Study in Healthy Subjects.
    Cannabis Cannabinoid Res, 2020 · Design: not stated · abstract only (PubMed) · open access (green)
    PMID 32322680DOI 10.1089/can.2019.0024PMC7173681 (free full text)
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Materials and Methods: Thus, we tested the plasma samples of 120 healthy human subjects (60 male and 60 female), 60 in fasting and the other 60 under normal feeding conditions after acute administration of an oral solution containing CBD 300 mg.
    • Food effect · abstract:Materials and Methods: Thus, we tested the plasma samples of 120 healthy human subjects (60 male and 60 female), 60 in fasting and the other 60 under normal feeding conditions after acute administration of an oral solution containing CBD 300 mg.
62. HumanFood effect on pharmacokinetics of cannabidiol oral capsules in adult patients with refractory epilepsy.
    Epilepsia, 2019 · Design: randomized · abstract only (PubMed) · closed/paywalled
    PMID 31247132DOI 10.1111/epi.16093
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Blood sampling for CBD plasma concentrations was performed under each condition between 0 and 72 hours post-dose and measured by a validated liquid chormatography-mass spectometry assay.
    • Key findings · abstract:CBD pharmacokinetic profiles including maximum concentration (Cmax ), area-under-the-curve from zero to infinity (AUC0-∞ ), and time-to-maximum concentration (Tmax ) were calculated.
    • Key findings · abstract:The confidence intervals (CIs) for log-transformed Cmax and AUC0-∞ ratios between fed and fasting states were calculated.
    • Key findings · abstract:On average Cmax was 14 times and AUC0-∞ 4 times higher in the fed state.
    • Key findings · abstract:The 90% CI for the ratio of[excerpt truncated in our database — see source]
    • Cmax · abstract:CBD pharmacokinetic profiles including maximum concentration (Cmax ), area-under-the-curve from zero to infinity (AUC0-∞ ), and time-to-maximum concentration (Tmax ) were calculated.
    • Cmax · abstract:The confidence intervals (CIs) for log-transformed Cmax and AUC0-∞ ratios between fed and fasting states were calculated.
    • Cmax · abstract:On average Cmax was 14 times and AUC0-∞ 4 times higher in the fed state.
    • Cmax · abstract:The 90% CI for the ratio of fed versus fast conditions for Cmax and AUC0-∞ were 7.47-31.86 and 3.42-7.82, respectively.
    • Cmax · abstract:No sequence or period effect for Cmax and AUC0-∞ was observed.
    • Cmax · abstract:The fat content of a meal can
    • Tmax · abstract:CBD pharmacokinetic profiles including maximum concentration (Cmax ), area-under-the-curve from zero to infinity (AUC0-∞ ), and time-to-maximum concentration (Tmax ) were calculated.
    • AUC · abstract:CBD pharmacokinetic profiles including maximum concentration (Cmax ), area-under-the-curve from zero to infinity (AUC0-∞ ), and time-to-maximum concentration (Tmax ) were calculated.
    • AUC · abstract:The confidence intervals (CIs) for log-transformed Cmax and AUC0-∞ ratios between fed and fasting states were calculated.
    • AUC · abstract:On average Cmax was 14 times and AUC0-∞ 4 times higher in the fed state.
    • AUC · abstract:The 90% CI for the ratio of fed versus fast conditions for Cmax and AUC0-∞ were 7.47-31.86 and 3.42-7.82, respectively.
    • AUC · abstract:No sequence or period effect for Cmax and AUC0-∞ was observed.
    • AUC · abstract:The fat content of a meal can
    • Food effect · abstract:A single dose of 99% pure CBD capsules was taken under both fasting (no breakfast) and fed (high fat 840-860 calorie) conditions.
    • Food effect · abstract:The confidence intervals (CIs) for log-transformed Cmax and AUC0-∞ ratios between fed and fasting states were calculated.
    • Food effect · abstract:On average Cmax was 14 times and AUC0-∞ 4 times higher in the fed state.
    • Food effect · abstract:The 90% CI for the ratio of fed versus fast conditions for Cmax and AUC0-∞ were 7.47-31.86 and 3.42-7.82, respectively.
63. HumanA Novel Self-Emulsifying Drug Delivery System (SEDDS) Based on VESIsorb® Formulation Technology Improving the Oral Bioavailability of Cannabidiol in Healthy Subjects.
    Molecules, 2019 · Design: randomized; crossover; double-blind · n: 16 healthy volunteers · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 31426272DOI 10.3390/molecules24162967PMC6720748 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:Single oral administration of SEDDS-CBD led to a 4.4-fold higher Cmax and a 2.85-/1.70-fold higher AUC0-8h/AUC0-24h compared to the reference formulation.
    • Cmax · abstract:Single oral administration of SEDDS-CBD led to a 4.4-fold higher Cmax and a 2.85-/1.70-fold higher AUC0-8h/AUC0-24h compared to the reference formulation.
    • Tmax · abstract:Tmax was substantially shorter for SEDDS-CBD (1.0 h) compared to MCT-CBD (3.0 h).
    • AUC · abstract:Single oral administration of SEDDS-CBD led to a 4.4-fold higher Cmax and a 2.85-/1.70-fold higher AUC0-8h/AUC0-24h compared to the reference formulation.
    • Relative bioavailability · abstract:Single oral administration of SEDDS-CBD led to a 4.4-fold higher Cmax and a 2.85-/1.70-fold higher AUC0-8h/AUC0-24h compared to the reference formulation.
    • Food effect · abstract:The study objective was to evaluate the pharmacokinetic profile of SEDDS-CBD in a randomized, double-blind, cross-over design in 16 healthy volunteers under fasted conditions.
    • Cmax · full text, Table 2:-emulsifying drug delivery system-cannabidiol (SEDDS-CBD) and medium-chain triglycerides-cannabidiol (MCT-CBD). Subjects Pharmacokinetic Parameters Cmax [ng/mL] AUC0-8h [ng/mL*h] AUC0-24h [ng/mL*h] Tmax [h] Mean (95% CI) Mean (95% CI) Mean (95% CI) Median (25th–75th percentile) MCT-CBD SEDDS-CBD p MCT-CBD SEDDS-CBD p MCT-CBD SEDDS-CBD p MCT-CBD SEDDS-CBD p All(n = 16)
    • Cmax · full text, Section '2.4. Effects of Gender on CBD Pharmacoki':In contrast, after ingestion of SEDDS-CBD the effects of gender on bioavailability were minor with no significant differences and comparable Cmax values (13.75 ng/mL (men) vs. 13.32 ng/mL (women) (p = 0.7209)).
    • Tmax · full text, Table 2:) and medium-chain triglycerides-cannabidiol (MCT-CBD). Subjects Pharmacokinetic Parameters Cmax [ng/mL] AUC0-8h [ng/mL*h] AUC0-24h [ng/mL*h] Tmax [h] Mean (95% CI) Mean (95% CI) Mean (95% CI) Median (25th–75th percentile) MCT-CBD SEDDS-CBD p MCT-CBD SEDDS-CBD p MCT-CBD SEDDS-CBD p MCT-CBD SEDDS-CBD p All(n = 16) 3.05 (1.57–4.54) 13.53 (7.96–19.10) <0.0001 9.51 (5.73–
    • Tmax · full text, Section '2.3. Pharmacokinetic Parameters':Tmax was 1.0 h for SEDDS-CBD and 3.0 h for MCT-CBD (Table 2).
    • Tmax · full text, Section '2.3. Pharmacokinetic Parameters':Despite the observed high inter-individual variability of the bioavailability of CBD in both formulations with a coefficient of variation of 58.58% for SEDDS-CBD vs. 74.66% for the reference product (data presented for AUC0–8h), the very fast absorption of CBD from SEDDS-CBD with Tmax values of ≤1 h was very homogeneously confirmed in 87.5% of subjects (maximum Tmax levels 2 h).
    • AUC · full text, Table 2:ug delivery system-cannabidiol (SEDDS-CBD) and medium-chain triglycerides-cannabidiol (MCT-CBD). Subjects Pharmacokinetic Parameters Cmax [ng/mL] AUC0-8h [ng/mL*h] AUC0-24h [ng/mL*h] Tmax [h] Mean (95% CI) Mean (95% CI) Mean (95% CI) Median (25th–75th percentile) MCT-CBD SEDDS-CBD p MCT-CBD SEDDS-CBD p MCT-CBD SEDDS-CBD p MCT-CBD SEDDS-CBD p All(n = 16) 3.05 (1.57–4.5
    • AUC · full text, Section '2.3. Pharmacokinetic Parameters':AUC0–8h of SEDDS-CBD was 2.85-fold higher compared to MCT-CBD (p < 0.0001).
    • AUC · full text, Section '2.3. Pharmacokinetic Parameters':The significant difference was also confirmed for AUC0–24h (p = 0.0021) (Table 2).
    • Relative bioavailability · full text, Section '2.3. Pharmacokinetic Parameters':AUC0–8h of SEDDS-CBD was 2.85-fold higher compared to MCT-CBD (p < 0.0001).
    • Relative bioavailability · full text, Section '2.4. Effects of Gender on CBD Pharmacoki':For MCT-CBD, the AUC0–8h and AUC0–24h values were 2.4-fold (p = 0.0192) and 1.5-fold (p = 0.0499) higher in women than in men (Table 2).
    • Form comparison · full text, Section '2.2. CBD Plasma Concentration Time Profi':For SEDDS-CBD the concentration was significantly increased starting from 0.5 h to 6 h compared to baseline levels.
    • Form comparison · full text, Section '2.3. Pharmacokinetic Parameters':AUC0–8h of SEDDS-CBD was 2.85-fold higher compared to MCT-CBD (p < 0.0001).
    • Form comparison · full text, Section '2.3. Pharmacokinetic Parameters':Despite the observed high inter-individual variability of the bioavailability of CBD in both formulations with a coefficient of variation of 58.58% for SEDDS-CBD vs. 74.66% for the reference product (data presented for AUC0–8h), the very fast absorption of CBD from SEDDS-CBD with Tmax values of ≤1 h was very homogeneously confirmed in 87.5% of subjects (maximum Tmax levels 2 h).
64. HumanExamination of a New Delivery Approach for Oral Cannabidiol in Healthy Subjects: A Randomized, Double-Blinded, Placebo-Controlled Pharmacokinetics Study.
    Adv Ther, 2019 · Design: randomized; crossover; double-blind · n: 12 participants · abstract only (PubMed) · closed/paywalled
    PMID 31512143DOI 10.1007/s12325-019-01074-6
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:RESULTS: Although there were no differences in the 45 mg conditions, circulating CBD levels were higher with the TurboCBD™ 90 mg group at both 90 (+ 86%) and 120 (+ 65%) min compared with the 90 mg control (p < 0.05).
    • Key findings · abstract:Total area under the curve tended to be higher with TurboCBD™ 90 mg compared with 90 mg (10,865 ± 6322 ng ml-1 vs. 7114 ± 2978 ng ml-1; p = 0.088).
    • Key findings · abstract:Only the TurboCBD™ 90 mg dose was elevated greater than placebo at 30 min (p = 0.017) and remained elevated at 4 h (p = 0.002).
    • Key findings · abstract:CONCLUSION: Consistent with higher bioavailability, TurboCBD™ 90 mg at the peak CBD concentration wa[excerpt truncated in our database — see source]
    • AUC · abstract:Total area under the curve tended to be higher with TurboCBD™ 90 mg compared with 90 mg (10,865 ± 6322 ng ml-1 vs. 7114 ± 2978 ng ml-1; p = 0.088).
65. HumanPharmacokinetics and Tolerability of Multiple Doses of Pharmaceutical-Grade Synthetic Cannabidiol in Pediatric Patients with Treatment-Resistant Epilepsy.
    CNS Drugs, 2019 · Design: not stated · n: 61 patients · full text (Europe PMC XML) + abstract · open access (hybrid)
    PMID 31049885DOI 10.1007/s40263-019-00624-4PMC6534520 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:Concomitant administration of clobazam with 40 mg/kg/day of cannabidiol oral solution resulted in a 2.5-fold increase in mean cannabidiol exposure.
    • Key findings · abstract:Mean plasma clobazam concentrations were 1.7- and 2.2-fold greater in patients receiving clobazam concomitantly with 40 mg/kg/day of cannabidiol oral solution compared with 10 mg/kg/day and 20 mg/kg/day.
    • Key findings · abstract:Mean plasma norclobazam values were 1.3- and 1.9-fold higher for patients taking clobazam plus 40 mg/kg/day of cannabidiol oral solution compared with the 10-mg/kg/day and 20-mg/kg/day groups.
    • Relative bioavailability · abstract:Concomitant administration of clobazam with 40 mg/kg/day of cannabidiol oral solution resulted in a 2.5-fold increase in mean cannabidiol exposure.
    • Relative bioavailability · abstract:Mean plasma clobazam concentrations were 1.7- and 2.2-fold greater in patients receiving clobazam concomitantly with 40 mg/kg/day of cannabidiol oral solution compared with 10 mg/kg/day and 20 mg/kg/day.
    • Relative bioavailability · abstract:Mean plasma norclobazam values were 1.3- and 1.9-fold higher for patients taking clobazam plus 40 mg/kg/day of cannabidiol oral solution compared with the 10-mg/kg/day and 20-mg/kg/day groups.
    • Cmax · full text, Table 3:tients with epilepsy Cannabidiol oral solution cohort Day 1 (single dose) Day 10 (multiple dose) Tmax, h: median (range) t1/2, ha AUC(0–12), ng·h/mLa Cmax, ng/mLa Tmax, h: median (range) AUC(0–τ), ng·h/mLa Cmax, ng/mLa CLss/F, L/h/kga 10 mg/kg/day (n = 20) 2.6 (1.0–8.0) 26.4, 31.3 (74.9) 122, 173.9 (103.3) 29.12, 59.03 (169.4) 3.0 (1.0–4.2) 507.0, 581.6 (48.7) 91.0, 119.6 (87.8) 9.9, 12.1 (88.0) 2
    • Cmax · full text, Table 4:tients with epilepsy Cannabidiol oral solution cohort Day 1 (single dose) Day 10 (multiple dose) Tmax, h: median (range) t1/2, ha AUC(0–12), ng·h/mLa Cmax, ng/mLa Tmax, h: median (range) AUC(0–τ), ng·h/mLa Cmax, ng/mLa MRAUC(0–τ)a 10 mg/kg/day (n = 20) 2.6 (1.0–6.1) 18.4, 19.7 (38.8) 104.0, 124.4 (64.4) 22.03, 28.71 (93.1) 2.1 (1.0–4.1) 428.3, 513.4 (52.4) 65.6, 79.4 (51.4) 0.80, 0.88 (46.4) 20 mg
    • Cmax · full text, Table 5:10) 2520 (1567–4053) Infants vs. adolescents 38.67 (18.26–81.93)   Adolescents (n = 6) 2761 (1495–5097) Children vs. adolescents 91.30 (48.13–173.18) Cmax, ng/mL (95% CI)  Cohort 1, 10 mg/kg/day   Infants (n = 5) 55.89 (27.21–114.8) Infants vs. children 47.74 (22.78–100.07)   Children (n = 9) 117.1 (68.47–200.2) Infants vs. adolescents 59.70 (26.73–133.33)   Adolescents (n = 6) 93.61 (48.53–180.6)
    • Tmax · full text, Table 3:annabidiol pharmacokinetic parameters in pediatric patients with epilepsy Cannabidiol oral solution cohort Day 1 (single dose) Day 10 (multiple dose) Tmax, h: median (range) t1/2, ha AUC(0–12), ng·h/mLa Cmax, ng/mLa Tmax, h: median (range) AUC(0–τ), ng·h/mLa Cmax, ng/mLa CLss/F, L/h/kga 10 mg/kg/day (n = 20) 2.6 (1.0–8.0) 26.4, 31.3 (74.9) 122, 173.9 (103.3) 29.12, 59.03 (169.4) 3.0 (1.0–4.2) 507.
    • Tmax · full text, Table 4:annabidiol pharmacokinetic parameters in pediatric patients with epilepsy Cannabidiol oral solution cohort Day 1 (single dose) Day 10 (multiple dose) Tmax, h: median (range) t1/2, ha AUC(0–12), ng·h/mLa Cmax, ng/mLa Tmax, h: median (range) AUC(0–τ), ng·h/mLa Cmax, ng/mLa MRAUC(0–τ)a 10 mg/kg/day (n = 20) 2.6 (1.0–6.1) 18.4, 19.7 (38.8) 104.0, 124.4 (64.4) 22.03, 28.71 (93.1) 2.1 (1.0–4.1) 428.3, 5
    • AUC · full text, Table 3:ters in pediatric patients with epilepsy Cannabidiol oral solution cohort Day 1 (single dose) Day 10 (multiple dose) Tmax, h: median (range) t1/2, ha AUC(0–12), ng·h/mLa Cmax, ng/mLa Tmax, h: median (range) AUC(0–τ), ng·h/mLa Cmax, ng/mLa CLss/F, L/h/kga 10 mg/kg/day (n = 20) 2.6 (1.0–8.0) 26.4, 31.3 (74.9) 122, 173.9 (103.3) 29.12, 59.03 (169.4) 3.0 (1.0–4.2) 507.0, 581.6 (48.7) 91.0, 119.6 (87.8
    • AUC · full text, Table 4:ters in pediatric patients with epilepsy Cannabidiol oral solution cohort Day 1 (single dose) Day 10 (multiple dose) Tmax, h: median (range) t1/2, ha AUC(0–12), ng·h/mLa Cmax, ng/mLa Tmax, h: median (range) AUC(0–τ), ng·h/mLa Cmax, ng/mLa MRAUC(0–τ)a 10 mg/kg/day (n = 20) 2.6 (1.0–6.1) 18.4, 19.7 (38.8) 104.0, 124.4 (64.4) 22.03, 28.71 (93.1) 2.1 (1.0–4.1) 428.3, 513.4 (52.4) 65.6, 79.4 (51.4) 0.8
    • AUC · full text, Table 5:Age effects of cannabidiol exposure after multiple-dose administration Cohort Geometric LS mean Pairwise comparison Ratio, % (90% CI) AUC(0–τ), ng·h/mL (95% CI)  Cohort 1, 10 mg/kg/day   Infants (n = 5) 335.7 (197.8–569.8) Infants vs. children 52.73 (30.26–91.87)   Children (n = 8) 636.8 (419.2–967.3) Infants vs. adolescents 63.64 (35.29–114.79)   Adolescents (n = 6) 527.5 (325.5–854.
    • Relative bioavailability · full text, Section 'Influence of Clobazam Use':In patients receiving clobazam plus cannabidiol oral solution at a dose of 40 mg/kg/day, mean cannabidiol exposure on day 10 increased approximately 2.5-fold compared with patients not receiving clobazam (geometric mean AUC(0–τ), 3130 ng·h/mL vs. 1245 ng·h/mL, respectively;
    • Relative bioavailability · full text, Section 'Influence of Clobazam Use':On day 10, mean plasma clobazam concentrations were increased 1.7- and 2.2-fold in patients receiving clobazam concomitantly with cannabidiol oral solution of 40 mg/kg/day compared with 10 mg/kg/day and 20 mg/kg/day (857 ng/mL vs. 500 ng/mL and 390 ng/mL), respectively.
    • Relative bioavailability · full text, Section 'Influence of Clobazam Use':Similarly, mean plasma norclobazam concentrations on day 10 were increased 1.3- and 1.9-fold in patients receiving clobazam concomitantly with cannabidiol oral solution of 40 mg/kg/day compared with 10 mg/kg/day and 20 mg/kg/day (6111 ng/mL vs. 4750 ng/mL and 3224 ng/mL), respectively.
    • Form comparison · full text, Table 5:metric LS mean Pairwise comparison Ratio, % (90% CI) AUC(0–τ), ng·h/mL (95% CI)  Cohort 1, 10 mg/kg/day   Infants (n = 5) 335.7 (197.8–569.8) Infants vs. children 52.73 (30.26–91.87)   Children (n = 8) 636.8 (419.2–967.3) Infants vs. adolescents 63.64 (35.29–114.79)   Adolescents (n = 6) 527.5 (325.5–854.9) Children vs. adolescents 120.71 (71.33–204.26)  Cohort 2, 20 mg/kg/day   Infants (n = 4)a 7
    • Form comparison · full text, Section 'Age Assessment':The point estimates for infants vs. children or for infants vs. adolescents for Cmax and AUC(0–τ) ranged from 38.7 to 46.8%.
    • Form comparison · full text, Section 'Influence of Clobazam Use':In patients receiving clobazam plus cannabidiol oral solution at a dose of 40 mg/kg/day, mean cannabidiol exposure on day 10 increased approximately 2.5-fold compared with patients not receiving clobazam (geometric mean AUC(0–τ), 3130 ng·h/mL vs. 1245 ng·h/mL, respectively;
66. HumanA Phase 1, Open-Label, Parallel-Group, Single-Dose Trial of the Pharmacokinetics and Safety of Cannabidiol (CBD) in Subjects With Mild to Severe Hepatic Impairment.
    J Clin Pharmacol, 2019 · Design: not stated · n: n =  8 · full text (Europe PMC XML) + abstract · open access (hybrid)
    PMID 30921490DOI 10.1002/jcph.1412PMC6618279 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:CBD was rapidly absorbed in all groups independent of hepatic function (median time to maximum plasma concentration, 2-2.8 hours).
    • AUC · abstract:Exposure (area under the concentration-time curve from time zero to infinity) to total CBD slightly increased in subjects with mild hepatic impairment (geometric mean ratio [GMR], 1.48; 90% confidence interval [CI], 0.90-2.41).
    • Fractional absorption · abstract:CBD was rapidly absorbed in all groups independent of hepatic function (median time to maximum plasma concentration, 2-2.8 hours).
    • Cmax · full text, Table 3:Parameter Mild Hepatic Impairment (N = 8) Moderate Hepatic Impairment (N = 8) Severe Hepatic Impairment (N = 6) Normal Hepatic Function (N = 8) CBD Cmax (ng/mL) 233 (70.5) 354 (42.3) 381 (52.2) 148 (65.0) AUC0‐∞ (ng·h/mL)b 699 (44.2) 1163 (39.9) 2439 (29.5)d 474 (73.8) AUC0‐t (ng·h/mL) 648 (44.2) 1054 (38.9) 1855 (52.0) 449 (73.5) tmax 2.8 (1.5‐5.0) 2.0 (1.5‐3.0) 2.5 (2.0‐5.0) 2.3 (1.5‐5.0) t½
    • Cmax · full text, Table 4:rs Between Hepatic Impairment Groups and the Normal Hepatic Function Group: PK Analysis Set Ratio of Geometric Least Squares Means (90%CI) Comparison Cmax (ng/mL) AUC0‐∞ (ng·h/mL) AUC0‐t (ng·h/mL) CL/F (L/h) tmax a (h) CBD Mild/Normal 1.57 (0.90 to 2.75) 1.48 (0.90 to 2.41) 1.44 (0.86 to 2.41) 0.68 (0.41 to 1.11) 0.23 (–0.55 to 1.00) Moderate/Normal 2.39 (1.37 to 4.18) 2.45 (1.50 to 4.01) 2.35 (1.
    • Cmax · full text, Section 'Pharmacokinetics':Geometric mean Cmax was 233 ng/mL for mild, 354 ng/mL for moderate, and 381 ng/mL for severe hepatic impairment versus 148 ng/mL for subjects with normal hepatic function (Table 3).
    • Tmax · full text, Table 3:1 (52.2) 148 (65.0) AUC0‐∞ (ng·h/mL)b 699 (44.2) 1163 (39.9) 2439 (29.5)d 474 (73.8) AUC0‐t (ng·h/mL) 648 (44.2) 1054 (38.9) 1855 (52.0) 449 (73.5) tmax 2.8 (1.5‐5.0) 2.0 (1.5‐3.0) 2.5 (2.0‐5.0) 2.3 (1.5‐5.0) t½ (h)c 15.7 (58.3) 20.5 (39.2) 22.1 (44.9)d 8.58 (68.4) CL/F (L/h) 286 (44.2) 172 (39.9) 82.0 (29.5)d 422 (73.8) Vz/F (L) 5302 (60.1) 4668 (40.1) 2437 (70.5)d 4105 (37.5) 6‐OH‐CBD Cma
    • Tmax · full text, Table 4:c Function Group: PK Analysis Set Ratio of Geometric Least Squares Means (90%CI) Comparison Cmax (ng/mL) AUC0‐∞ (ng·h/mL) AUC0‐t (ng·h/mL) CL/F (L/h) tmax a (h) CBD Mild/Normal 1.57 (0.90 to 2.75) 1.48 (0.90 to 2.41) 1.44 (0.86 to 2.41) 0.68 (0.41 to 1.11) 0.23 (–0.55 to 1.00) Moderate/Normal 2.39 (1.37 to 4.18) 2.45 (1.50 to 4.01) 2.35 (1.41 to 3.92) 0.41 (0.25 to 0.67) –0.52 (–2.03 to 0.02) Seve
    • AUC · full text, Table 3:tic Impairment (N = 8) Severe Hepatic Impairment (N = 6) Normal Hepatic Function (N = 8) CBD Cmax (ng/mL) 233 (70.5) 354 (42.3) 381 (52.2) 148 (65.0) AUC0‐∞ (ng·h/mL)b 699 (44.2) 1163 (39.9) 2439 (29.5)d 474 (73.8) AUC0‐t (ng·h/mL) 648 (44.2) 1054 (38.9) 1855 (52.0) 449 (73.5) tmax 2.8 (1.5‐5.0) 2.0 (1.5‐3.0) 2.5 (2.0‐5.0) 2.3 (1.5‐5.0) t½ (h)c 15.7 (58.3) 20.5 (39.2) 22.1 (44.9)d 8.58 (68.4)
    • AUC · full text, Table 4:patic Impairment Groups and the Normal Hepatic Function Group: PK Analysis Set Ratio of Geometric Least Squares Means (90%CI) Comparison Cmax (ng/mL) AUC0‐∞ (ng·h/mL) AUC0‐t (ng·h/mL) CL/F (L/h) tmax a (h) CBD Mild/Normal 1.57 (0.90 to 2.75) 1.48 (0.90 to 2.41) 1.44 (0.86 to 2.41) 0.68 (0.41 to 1.11) 0.23 (–0.55 to 1.00) Moderate/Normal 2.39 (1.37 to 4.18) 2.45 (1.50 to 4.01) 2.35 (1.41 to 3.92) 0
    • AUC · full text, Section 'Pharmacokinetics':Respective geometric mean AUC0‐t and AUC0‐∞ were 648 and 699 ng·h/mL for subjects with mild, 1054 and 1163 ng·h/mL for subjects with moderate, and 1855 and 2439 ng·h/mL for subjects with severe hepatic impairment versus 449 and 474 ng·h/mL for subjects with normal hepatic function.
    • Form comparison · full text, Section 'Pharmacokinetics':Geometric mean Cmax was 233 ng/mL for mild, 354 ng/mL for moderate, and 381 ng/mL for severe hepatic impairment versus 148 ng/mL for subjects with normal hepatic function (Table 3).
    • Form comparison · full text, Section 'Pharmacokinetics':Respective geometric mean AUC0‐t and AUC0‐∞ were 648 and 699 ng·h/mL for subjects with mild, 1054 and 1163 ng·h/mL for subjects with moderate, and 1855 and 2439 ng·h/mL for subjects with severe hepatic impairment versus 449 and 474 ng·h/mL for subjects with normal hepatic function.
    • Form comparison · full text, Section 'Pharmacokinetics':Statistical analysis showed AUC0‐∞ was increased slightly in subjects with mild hepatic impairment compared with those with normal hepatic function (geometric mean ratio [GMR, 1.48; 90%CI 0.90‐2.41]), and significantly increased in subjects with moderate (GMR, 2.45; 90%CI, 1.50‐4.01) or severe (GMR, 5.15; 90%CI, 2.94‐9.00) hepatic impairment relative to subjects with normal hepatic function (Table
67. HumanCorrection to: A Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Dose, and Food Effect Trial of the Safety, Tolerability and Pharmacokinetics of Highly Purified Cannabidiol in Healthy Subjects.
    CNS Drugs, 2019 · Design: not stated · abstract only (PubMed) · open access (bronze)
    PMID 30830575DOI 10.1007/s40263-019-00617-3PMC6828038 (free full text)
    Verification: abstract-only auto-extract; unverified
68. HumanSingle-Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology.
    Clin Pharmacol Drug Dev, 2018 · Design: randomized; crossover · abstract only (PubMed) · closed/paywalled
    PMID 29125702DOI 10.1002/cpdd.408
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Study objectives were to evaluate the safety and tolerability of PTL101 containing 10 and 100 mg CBD, following single administrations to healthy volunteers and to compare the pharmacokinetic profiles and relative bioavailability of CBD with Sativex oromucosal spray (the reference product) in a randomized, crossover study design.
    • Key findings · abstract:Administration of PTL101 containing 10 CBD, led to a 1.7-fold higher Cmax and 1.3-fold higher AUC compared with the oromucosal spray.
    • Key findings · abstract:CBD exhibited about a 1-hour lag in absorption when delivered via PTL101.
    • Key findings · abstract:A 10-fold increase in the dose resulted in an ∼15-fold[excerpt truncated in our database — see source]
    • Cmax · abstract:Administration of PTL101 containing 10 CBD, led to a 1.7-fold higher Cmax and 1.3-fold higher AUC compared with the oromucosal spray.
    • Cmax · abstract:A 10-fold increase in the dose resulted in an ∼15-fold increase in Cmax and AUC.
    • Tmax · abstract:Tmax following both modes of delivery was 3-3.5 hours postdosing.
    • AUC · abstract:Administration of PTL101 containing 10 CBD, led to a 1.7-fold higher Cmax and 1.3-fold higher AUC compared with the oromucosal spray.
    • AUC · abstract:A 10-fold increase in the dose resulted in an ∼15-fold increase in Cmax and AUC.
    • Relative bioavailability · abstract:Study objectives were to evaluate the safety and tolerability of PTL101 containing 10 and 100 mg CBD, following single administrations to healthy volunteers and to compare the pharmacokinetic profiles and relative bioavailability of CBD with Sativex oromucosal spray (the reference product) in a randomized, crossover study design.
    • Relative bioavailability · abstract:Administration of PTL101 containing 10 CBD, led to a 1.7-fold higher Cmax and 1.3-fold higher AUC compared with the oromucosal spray.
    • Relative bioavailability · abstract:A 10-fold increase in the dose resulted in an ∼15-fold increase in Cmax and AUC.
69. HumanA Phase I, Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose, Multiple Dose, and Food Effect Trial of the Safety, Tolerability and Pharmacokinetics of Highly Purified Cannabidiol in Healthy Subjects.
    CNS Drugs, 2018 · Design: randomized · n: n = 6 · full text (Europe PMC XML) + abstract · open access (hybrid)
    PMID 30374683DOI 10.1007/s40263-018-0578-5PMC6223703 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:After single oral doses, CBD appeared rapidly in plasma; time to maximum plasma concentration (tmax) was approximately 4-5 h.
    • Key findings · abstract:Plasma exposure to CBD [maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to time t (AUCt)] increased in a less than dose-proportional manner (Cmax slope 0.73;[excerpt truncated in our database — see source]
    • Key findings · abstract:AUCt slope 0.64).
    • Key findings · abstract:CBD reached steady state after approximately 2 days, with moderate accumulation (1.8- to 2.6-fold) after 750 and 1500 mg CBD twice daily.
    • Key findings · abstract:After 7 days, a twofold increase in CBD dose resulted in 1.6- and 1.9-fold increases in geometric[excerpt truncated in our database — see source]
    • Cmax · abstract:Plasma exposure to CBD [maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to time t (AUCt)] increased in a less than dose-proportional manner (Cmax slope 0.73;
    • Cmax · abstract:After 7 days, a twofold increase in CBD dose resulted in 1.6- and 1.9-fold increases in geometric mean Cmax and area under the plasma concentration-time curve over a dosing interval (AUCτ), respectively.
    • Cmax · abstract:Cmax was 541.2 ng/mL and AUCτ was 3236 ng·h/mL after 1500 mg CBD twice daily.
    • Cmax · abstract:A high-fat meal increased CBD plasma exposure (Cmax and AUCt) by 4.85- and 4.2-fold, respectively; t
    • Tmax · abstract:After single oral doses, CBD appeared rapidly in plasma; time to maximum plasma concentration (tmax) was approximately 4-5 h.
    • Tmax · abstract:A high-fat meal increased CBD plasma exposure (Cmax and AUCt) by 4.85- and 4.2-fold, respectively; there was no effect of food on tmax or terminal half-life.
    • AUC · abstract:Plasma exposure to CBD [maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to time t (AUCt)] increased in a less than dose-proportional manner (Cmax slope 0.73;
    • AUC · abstract:AUCt slope 0.64).
    • AUC · abstract:After 7 days, a twofold increase in CBD dose resulted in 1.6- and 1.9-fold increases in geometric mean Cmax and area under the plasma concentration-time curve over a dosing interval (AUCτ), respectively.
    • AUC · abstract:Cmax was 541.2 ng/mL and AUCτ was 3236 ng·h/mL after 1500 mg CBD twice daily.
    • AUC · abstract:A high-fat meal increased CBD plasma exposure (Cmax and AUCt) by 4.85- and 4.2-f
    • Relative bioavailability · abstract:CBD reached steady state after approximately 2 days, with moderate accumulation (1.8- to 2.6-fold) after 750 and 1500 mg CBD twice daily.
    • Relative bioavailability · abstract:After 7 days, a twofold increase in CBD dose resulted in 1.6- and 1.9-fold increases in geometric mean Cmax and area under the plasma concentration-time curve over a dosing interval (AUCτ), respectively.
    • Relative bioavailability · abstract:A high-fat meal increased CBD plasma exposure (Cmax and AUCt) by 4.85- and 4.2-fold, respectively; there was no effect of food on tmax or terminal half-life.
    • Food effect · abstract:METHODS: The study consisted of three arms: single ascending dose (1500, 3000, 4500 or 6000 mg CBD [n = 6 per group]/placebo [n = 8; 2 per CBD dose group]), multiple dose (750 or 1500 mg CBD [n = 9 per group]/placebo [n = 6; 3 per CBD dose group] twice daily), and food effect (1500 mg CBD single dose [n = 12]).
    • Food effect · abstract:A high-fat meal increased CBD plasma exposure (Cmax and AUCt) by 4.85- and 4.2-fold, respectively; there was no effect of food on tmax or terminal half-life.
    • Cmax · full text, Table 7:of the trial Pharmacokinetic parameter (unit) 750 mg CBD (n = 9) 1500 mg CBD (n = 9) Day 1, am Day 1, pm Day 7, am Day 1, am Day 1, pm Day 7, am CBD  Cmax (ng/mL)a 290.8 (86.3) 732.4 (39.4) 330.3 (40.8) 361.8 (105.8) 1385 (52.4) 541.2 (53.7)  AUCτ (ng·h/mL)a 1070 (74.6) 2683 (33.4)d 1745 (38.4) 1444 (101.4) 9819 (32.3)e 3236 (44.0)  tmax (h)b 5.00 (2.50–5.00) 2.50 (2.00–5.00) 3.00 (2.50–5.00) 5.00
    • Cmax · full text, Table 8:iol and metabolites for the food effect arm of the trial Pharmacokinetic parameter (unit) 1500 mg CBD, fasted (n = 12) 1500 mg CBD, fed (n = 12) CBD  Cmax (ng/mL)a 335.4 (81.3) 1628 (51.4)  AUCt (ng·h/mL)a 1987 (53.6) 8347 (34.1)  AUC∞ (ng·h/mL)a 2198 (48.2) 8669 (33.9)  tmax (h)b 3.50 (2.50–5.03) 3.00 (1.50–5.00)  t½,z (h)c 30.33 (28.5) 24.40 (16.0)  CL/F (L/h)c 751.8 (46.6) 182.0 (34.2)  Vz/F (L
    • Cmax · full text, Section 'Single Ascending Dose PK':Figure 1 shows the geometric mean plasma concentration-time profiles, and Table 6 summarizes the PK parameters of CBD and its metabolites after single CBD doses.Fig. 1Single ascending CBD dose (1500, 3000, 4500 or 6000 mg) geometric mean plasma concentration-time profiles for CBD and its major metabolites (semi-logarithmic scale; pharmacokinetic set). 6-OH-CBD 6-hydroxy-cannabidiol, 7-OH-CBD 7-hyd
    • Tmax · full text, Table 7:9.4) 330.3 (40.8) 361.8 (105.8) 1385 (52.4) 541.2 (53.7)  AUCτ (ng·h/mL)a 1070 (74.6) 2683 (33.4)d 1745 (38.4) 1444 (101.4) 9819 (32.3)e 3236 (44.0)  tmax (h)b 5.00 (2.50–5.00) 2.50 (2.00–5.00) 3.00 (2.50–5.00) 5.00 (2.50–5.00) 4.00 (2.50–5.00) 3.00 (2.00–4.00)  t½,z (h)c – – 56.41 (32.6) – – 60.54 (20.2)  Racc – 2.914 (44.7) 1.795 (45.4) – 6.319 (62.8) 2.618 (59.3) 6-OH-CBD  Cmax (ng/mL)a 8.2 (82
    • Tmax · full text, Table 8:0 mg CBD, fed (n = 12) CBD  Cmax (ng/mL)a 335.4 (81.3) 1628 (51.4)  AUCt (ng·h/mL)a 1987 (53.6) 8347 (34.1)  AUC∞ (ng·h/mL)a 2198 (48.2) 8669 (33.9)  tmax (h)b 3.50 (2.50–5.03) 3.00 (1.50–5.00)  t½,z (h)c 30.33 (28.5) 24.40 (16.0)  CL/F (L/h)c 751.8 (46.6) 182.0 (34.2)  Vz/F (L/h)c 34,101 (60.5) 6349 (31.6) 6-OH-CBD  Cmax (ng/mL)a 9.6 (47.7) 26.8 (47.0)  AUCt (ng·h/mL)a 96.93 (44.0) 255.6 (40.2)
    • Tmax · full text, Section 'Single Ascending Dose PK':Figure 1 shows the geometric mean plasma concentration-time profiles, and Table 6 summarizes the PK parameters of CBD and its metabolites after single CBD doses.Fig. 1Single ascending CBD dose (1500, 3000, 4500 or 6000 mg) geometric mean plasma concentration-time profiles for CBD and its major metabolites (semi-logarithmic scale; pharmacokinetic set). 6-OH-CBD 6-hydroxy-cannabidiol, 7-OH-CBD 7-hyd
    • AUC · full text, Table 7:m Day 1, pm Day 7, am Day 1, am Day 1, pm Day 7, am CBD  Cmax (ng/mL)a 290.8 (86.3) 732.4 (39.4) 330.3 (40.8) 361.8 (105.8) 1385 (52.4) 541.2 (53.7)  AUCτ (ng·h/mL)a 1070 (74.6) 2683 (33.4)d 1745 (38.4) 1444 (101.4) 9819 (32.3)e 3236 (44.0)  tmax (h)b 5.00 (2.50–5.00) 2.50 (2.00–5.00) 3.00 (2.50–5.00) 5.00 (2.50–5.00) 4.00 (2.50–5.00) 3.00 (2.00–4.00)  t½,z (h)c – – 56.41 (32.6) – – 60.54 (20.2)
    • AUC · full text, Table 8:arm of the trial Pharmacokinetic parameter (unit) 1500 mg CBD, fasted (n = 12) 1500 mg CBD, fed (n = 12) CBD  Cmax (ng/mL)a 335.4 (81.3) 1628 (51.4)  AUCt (ng·h/mL)a 1987 (53.6) 8347 (34.1)  AUC∞ (ng·h/mL)a 2198 (48.2) 8669 (33.9)  tmax (h)b 3.50 (2.50–5.03) 3.00 (1.50–5.00)  t½,z (h)c 30.33 (28.5) 24.40 (16.0)  CL/F (L/h)c 751.8 (46.6) 182.0 (34.2)  Vz/F (L/h)c 34,101 (60.5) 6349 (31.6) 6-OH-CBD
    • AUC · full text, Section 'Single Ascending Dose PK':Figure 1 shows the geometric mean plasma concentration-time profiles, and Table 6 summarizes the PK parameters of CBD and its metabolites after single CBD doses.Fig. 1Single ascending CBD dose (1500, 3000, 4500 or 6000 mg) geometric mean plasma concentration-time profiles for CBD and its major metabolites (semi-logarithmic scale; pharmacokinetic set). 6-OH-CBD 6-hydroxy-cannabidiol, 7-OH-CBD 7-hyd
    • Relative bioavailability · full text, Section 'Multiple Dose PK':Cmax increased by approximately 1.6-fold (330 and 541 ng/mL after 750 and 1500 mg CBD, respectively, on day 7) and AUCτ increased by approximately 1.9-fold (1745 and 3236 ng·h/mL for 750 and 1500 mg CBD, respectively, on day 7).
    • Relative bioavailability · full text, Section 'Multiple Dose PK':There was moderate accumulation with multiple CBD doses; on the morning of day 7, compared with the morning of day 1, Rac increased by 1.8- and 2.6-fold after 750 and 1500 mg CBD doses, respectively.
    • Relative bioavailability · full text, Section 'Multiple Dose PK':The extent of accumulation was similar for CBD metabolites, except 7-COOH-CBD, for which Rac was 4.5- and 9.6-fold after 750 and 1500 mg CBD, respectively.
    • Food effect · full text, Table 8:Pharmacokinetic parameters of cannabidiol and metabolites for the food effect arm of the trial Pharmacokinetic parameter (unit) 1500 mg CBD, fasted (n = 12) 1500 mg CBD, fed (n = 12) CBD  Cmax (ng/mL)a 335.4 (81.3) 1628 (51.4)  AUCt (ng·h/mL)a 1987 (53.6) 8347 (34.1)  AUC∞ (ng·h/mL)a 2198 (48.2) 8669 (33.9)  tmax (h)b 3.50 (2.50–5.03) 3.00 (1.50–5.00)  t½,z (h)c 30.33 (28.5) 24.40 (16.0)  CL/F
    • Food effect · full text, Section 'Multiple Dose Arm':A separate cohort of 24 subjects was enrolled, and two groups of 12 healthy subjects received multiple oral doses of 750 or 1500 mg CBD (n = 9 per group) or matching placebo (n = 3 per group) twice daily under fasted conditions.
    • Food effect · full text, Section 'Food Effect Arm':Twelve randomly selected subjects from the SAD arm, irrespective of group (excluding subjects randomized to the 6000 mg group) or investigational medicinal product (IMP) taken in the SAD arm (CBD or placebo), crossed over into the FE arm to receive a single oral dose of 1500 mg CBD in either the fed (high-fat breakfast) or fasted state before crossing over.
    • Form comparison · full text, Section 'Safety and Tolerability of Cannabidiol (':Most notably, headache and dizziness affected 8 (33%) and 4 (17%) subjects taking CBD, respectively, compared with no subjects taking placebo.
    • Form comparison · full text, Section 'Safety and Tolerability of Cannabidiol (':Most TEAEs in the gastrointestinal disorders SOC affected a greater proportion of subjects taking CBD than placebo, most notably diarrhea [12 (67%) subjects taking CBD vs. 0 subjects taking placebo] and nausea [8 (44%) subjects taking CBD vs. 1 (17%) subject taking placebo].
    • Form comparison · full text, Section 'Safety and Tolerability of Cannabidiol (':In addition, more subjects taking CBD were affected by TEAEs in the nervous system disorders SOC than subjects taking placebo, most notably headache [8 (44%) subjects taking CBD vs. 0 subjects taking placebo], dizziness [3 (33%) subjects taking CBD vs. 0 subjects taking placebo] and presyncope [3 (33%) subjects taking CBD vs. 0 subjects taking placebo].
70. HumanA phase I study to assess the effect of food on the single dose bioavailability of the THC/CBD oromucosal spray.
    Eur J Clin Pharmacol, 2013 · Design: crossover · n: 7 subjects · abstract only (PubMed) · closed/paywalled
    PMID 23052407DOI 10.1007/s00228-012-1393-4
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:PURPOSE: To assess the effect of food on the single-dose bioavailability of delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray, an endocannabinoid system modulator, when administered to healthy male subjects.
    • Key findings · abstract:Plasma samples were collected at designated time-points for analysis of CBD, THC, and its active metabolite, 11-hydroxy delta-9-tetrahydrocannabinol (11-OH-THC).
    • Key findings · abstract:Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions.
    • Key findings · abstract:The Cmax for THC in fed versus fasted subjects was higher in 7 subjec[excerpt truncated in our database — see source]
    • Cmax · abstract:Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions.
    • Cmax · abstract:The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80-14.91 ng/ml) and lower in 5 subjects (2.81-3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97-9.34 ng/ml) observed in the fasted state.
    • Cmax · abstract:Increases in mean AUC(0-t), AUC(0-inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable.
    • Tmax · abstract:Food also appeared to delay the time to peak concentration (Tmax) of all analytes by approximately 2-2.5 h.
    • AUC · abstract:Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions.
    • AUC · abstract:Increases in mean AUC(0-t), AUC(0-inf), and Cmax for THC, CBD, and 11-OH-THC in the fed state were within the range of inter-subject variability, which was considerable.
    • Relative bioavailability · abstract:Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions.
    • Food effect · abstract:METHODS: Twelve subjects took part in this fed-fasted cross-over study and received a single dose of THC/CBD spray (4 sprays = 10.8 mg THC + 10 mg CBD) in the fasted then fed state (or vice versa) with a 3-day wash-out period between treatments.
    • Food effect · abstract:Mean AUC and Cmax were one to three-fold higher for THC and 11-OH-THC, and five and three-fold higher for CBD respectively during fed conditions.
    • Food effect · abstract:The Cmax for THC in fed versus fasted subjects was higher in 7 subjects (4.80-14.91 ng/ml) and lower in 5 subjects (2.81-3.51 ng/ml) compared with the mean Cmax of 3.98 ng/ml (range 0.97-9.34 ng/ml) obser
71. HumanA phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray.
    Eur J Clin Pharmacol, 2013 · Design: randomized · abstract only (PubMed) · closed/paywalled
    PMID 23179176DOI 10.1007/s00228-012-1441-0
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Plasma samples were analyzed by gas chromatography-mass spectrometry for CBD, THC, and its primary metabolite 11-hydroxy-THC, and various PK parameters were investigated.
    • Key findings · abstract:RESULTS: Δ(9)-Tetrahydrocannabinol and CBD were rapidly absorbed following single-dose administration.
    • Key findings · abstract:CONCLUSIONS: The mean Cmax values (<12 ng/mL) recorded in this study were well below those reported in patients who smoked/inhaled cannabis, which is reassuring since elevated Cmax values are linked to significant psychoactivity.
    • Cmax · abstract:CONCLUSIONS: The mean Cmax values (<12 ng/mL) recorded in this study were well below those reported in patients who smoked/inhaled cannabis, which is reassuring since elevated Cmax values are linked to significant psychoactivity.
    • Fractional absorption · abstract:RESULTS: Δ(9)-Tetrahydrocannabinol and CBD were rapidly absorbed following single-dose administration.
    • Food effect · abstract:METHODS: Subjects received either single doses of THC/CBD spray as multiple sprays [2 (5.4 mg THC and 5.0 mg CBD), 4 (10.8 mg THC and 10.0 mg CBD) or 8 (21.6 mg THC and 20.0 mg CBD) daily sprays] or multiple doses of THC/CBD spray (2, 4 or 8 sprays once daily) for nine consecutive days, following fasting for a minimum of 10 h overnight prior to each dosing.
72. PrimatePharmacokinetics of cannabidiol and its metabolites in rhesus monkeys and New Zealand White rabbits.
    Toxicol Sci, 2025 · Design: not stated · abstract only (PubMed) · closed/paywalled
    PMID 40973479DOI 10.1093/toxsci/kfaf129
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:We have investigated if the pharmacokinetics of CBD in rhesus monkeys and New Zealand White rabbits is similar to humans by measuring serum levels of CBD and its phase I and II metabolites after single intragastric (77.5 mg/kg body weight) or intravenous (3.9 mg/kg body weight) CBD doses.
    • Key findings · abstract:In rhesus monkeys, intragastric CBD yielded a maximum concentration (Cmax) of 241.6 nM (males) and 476.5 nM (females), with a terminal half-life (T1/2) of 11.6 and 15.4 h.
    • Key findings · abstract:The area under the curve from zero to infinity (AUC0-inf) was 5,376 nM*h (males) and 7,366 nM*h (females), with bioavailability of 2.5[excerpt truncated in our database — see source]
    • Cmax · abstract:In rhesus monkeys, intragastric CBD yielded a maximum concentration (Cmax) of 241.6 nM (males) and 476.5 nM (females), with a terminal half-life (T1/2) of 11.6 and 15.4 h.
    • Cmax · abstract:The area under the curve from zero to infinity (AUC0-inf) was 5,376 nM*h (males) and 7,366 nM*h (females), with bioavailability of 2.5% and 5.5%. 7-Carboxy-CBD showed a Cmax of 334.7 nM (males) and 655.4 nM (females), with AUC0-inf 1.5 to 1.6 times higher than CBD.
    • Cmax · abstract:In rabbits, intragastric CBD resulted in a Cmax of 76.6 nM (males) and 117.1 nM (females), with a T1/2 of 11.1 and 14.9 h.
    • Cmax · abstract:The AUC0-inf was 1,443 nM*h (male
    • AUC · abstract:The area under the curve from zero to infinity (AUC0-inf) was 5,376 nM*h (males) and 7,366 nM*h (females), with bioavailability of 2.5% and 5.5%. 7-Carboxy-CBD showed a Cmax of 334.7 nM (males) and 655.4 nM (females), with AUC0-inf 1.5 to 1.6 times higher than CBD.
    • AUC · abstract:The AUC0-inf was 1,443 nM*h (males) and 1,645 nM*h (females), with bioavailability of 2.1% to 2.2%. 7-Carboxy-CBD levels were significantly higher than CBD, with a Cmax of 11,631 nM (males) and 13,278 nM (females), and an AUC0-inf 120 to 133 times higher.
73. PigSelection of In Vivo Relevant Dissolution Test Parameters for the Development of Cannabidiol Formulations with Enhanced Oral Bioavailability.
    Pharmaceutics, 2025 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 39861727DOI 10.3390/pharmaceutics17010079PMC11769287 (free full text)PDF
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Food effect · full text, Section '2.2.6. In Vivo Pharmacokinetic Data':Briefly, amorphous and lipid-based formulations (which contained an equivalent of 2.5 mg/kg of CBD) were administered orally to fasted piglets (n = 5 mean weight of 15 kg) and plasma collected at times zero, 1 h, 2 h, 2.5 h, 3 h, 3.5 h, 4 h, 4.5 h, 5 h, 5.5 h, 6 h, 7 h, 8 h, 12 h and 24 h was analyzed by a validated UHPLC–MS/MS method [18].
74. PigEvaluation of amorphous and lipid-based formulation strategies to increase the in vivo cannabidiol bioavailability in piglets.
    Int J Pharm, 2024 · Design: crossover · abstract (PubMed); full-text PDF saved · open access (green)
    PMID 38685441DOI 10.1016/j.ijpharm.2024.124173PDF
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:CBD and 7 - COOH - CBD, a secondary metabolite used as an indicator of hepatic degradation, were analyzed in plasma.
    • Key findings · abstract:A 10.9-fold and 6.8-fold increase in oral bioavailability was observed for the amorphous and lipid formulations, respectively.
    • Relative bioavailability · abstract:A 10.9-fold and 6.8-fold increase in oral bioavailability was observed for the amorphous and lipid formulations, respectively.
    • Cmax · full text, p.8:software and TargetLynx Version 4.2 software. 237 Pharmacokinetic analysis 238 Concentrations versus time in vivo data and pharmacokinetic parameters Cmax, Tmax and 239 AUClast were analyzed by a non-compartmental pharmacokinetic analysis using PhoenixTM 240 WinNonlin 8.4 (Certara, Princeton, USA). Linear trapezoidal linear interpolation calculation 241 method was applied for AUClast, Cmax corresp
    • Cmax · full text, p.13:he amorphous and lipid-based curves 334 never show similar exponential phases from T0 to Tmax for a same piglet. Pharmacokinetic 335 parameters Tmax, Cmax, and AUClast calculated from the data using the six piglets showed 336 higher variability for the amorphous formulation in comparison with the lipid-based 337 formulation (Table S1, Supplementary materials). This may be due to the fact that the
    • Cmax · full text, p.15:348 As the fourth piglet (P4) showed a completely different behavior and showed a high AUC and 349 Cmax for the crystalline form of CBD, it was decided to exclude this piglet from the main 350 analysis since it modified considerably the results and biased the bioavailability assessment. 351 Attention has to be made on the fact that the results directl
    • Tmax · full text, p.8:re and TargetLynx Version 4.2 software. 237 Pharmacokinetic analysis 238 Concentrations versus time in vivo data and pharmacokinetic parameters Cmax, Tmax and 239 AUClast were analyzed by a non-compartmental pharmacokinetic analysis using PhoenixTM 240 WinNonlin 8.4 (Certara, Princeton, USA). Linear trapezoidal linear interpolation calculation 241 method was applied for AUClast, Cmax correspond to
    • Tmax · full text, p.13:gh 333 variability between the animals. It is observed that the amorphous and lipid-based curves 334 never show similar exponential phases from T0 to Tmax for a same piglet. Pharmacokinetic 335 parameters Tmax, Cmax, and AUClast calculated from the data using the six piglets showed 336 higher variability for the amorphous formulation in comparison with the lipid-based 337 formulation (Table S1, Su
    • Tmax · full text, p.15:ased the bioavailability assessment. 351 Attention has to be made on the fact that the results directly depend on the variability. In 352 particular, Tmax values are highly influenced by the presence of at least two peaks for the 353 amorphous formulation while the crystalline and lipid-based formulations have mostly one 354 single peak. Tmax is indeed associated with the Cmax and not always with
    • AUC · full text, p.8:Lynx Version 4.2 software. 237 Pharmacokinetic analysis 238 Concentrations versus time in vivo data and pharmacokinetic parameters Cmax, Tmax and 239 AUClast were analyzed by a non-compartmental pharmacokinetic analysis using PhoenixTM 240 WinNonlin 8.4 (Certara, Princeton, USA). Linear trapezoidal linear interpolation calculation 241 method was applied for AUClast, Cmax correspond to the highest
    • AUC · full text, p.13:us and lipid-based curves 334 never show similar exponential phases from T0 to Tmax for a same piglet. Pharmacokinetic 335 parameters Tmax, Cmax, and AUClast calculated from the data using the six piglets showed 336 higher variability for the amorphous formulation in comparison with the lipid-based 337 formulation (Table S1, Supplementary materials). This may be due to the fact that the 338 formul
    • AUC · full text, p.15:348 As the fourth piglet (P4) showed a completely different behavior and showed a high AUC and 349 Cmax for the crystalline form of CBD, it was decided to exclude this piglet from the main 350 analysis since it modified considerably the results and biased the bioavailability assessment. 351 Attention has to be made on the fact that the re
    • Relative bioavailability · full text, p.22:496 increased the bioavailability of CBD by 10.9-fold and 6.8-fold for the amorphous and lipid 497 formulations, respectively. A high inter piglet variability has been highlighted as well as a 498 potential enterohepatic cycle mainly for the amorphous formulation. The simultaneous 499 quantification of
    • Food effect · full text, p.6:olled by the STARe System software. 173 Concentration at saturation of CBD in FaSSIF medium 174 The concentration at saturation of raw CBD in FaSSIF (fasted stated simulated intestinal 175 fluid) has been determined by adding excess of CBD in media placed in a water bath set at 176 37 °C and a rotating speed of 100 rpm during 24 hours (triplicate). After this time, the 177 suspension was filtered
    • Food effect · full text, p.7:2013 on the protection of experimental animals, A.G.W. 30.11.2017». 196 Per os study was conducted by given orally an equivalent of 2.5 mg CBD/kg in fasted sate. 197 This dosage was selected based on Epidiolex® posology and dosage form volume. The 198 amorphous and lipid-based formulations were compared to the crystalline CBD. All 199 formulation were sealed manually in gelatin 00 sized capsules w
    • Food effect · full text, p.10:3 mixture 270 inside the mesopores, which must then exit the silica pores by diffusion. 271 In vitro dissolution test 272 FaSSIF medium simulates the fasted intestinal fluid with a pH of 6.5 and contained 3 mM of 273 taurocholate and 0.75 mM of phospholipids, namely lecithin. This media mimics the intestinal 274 fluids in terms of pH, isotonicity and surfactant characteristics, under fasted condit
    • Form comparison · full text, p.7:in fasted sate. 197 This dosage was selected based on Epidiolex® posology and dosage form volume. The 198 amorphous and lipid-based formulations were compared to the crystalline CBD. All 199 formulation were sealed manually in gelatin 00 sized capsules without any additional 200 excipient and administered by force-feeding system. Six Large White piglets (male and 201 female, between 8 and 20 kg) b
    • Form comparison · full text, p.8:acquisition was achieved 236 using MassLynx Version 4.2 software and TargetLynx Version 4.2 software. 237 Pharmacokinetic analysis 238 Concentrations versus time in vivo data and pharmacokinetic parameters Cmax, Tmax and 239 AUClast were analyzed by a non-compartmental pharmacokinetic analysis using PhoenixTM 240 WinNonlin 8.4 (Certara, Princeton, USA). Linear trapezoidal linear interpolation calc
    • Form comparison · full text, p.9:e for all the 260 duration of the current in vitro and in vivo experiments. 261 262 Figure 1 – Thermograms of amorphous and lipid-based formulations, compared to the crystalline CBD
75. PigPlasma and joint tissue pharmacokinetics of two doses of oral cannabidiol oil in guinea pigs (Cavia porcellus).
    J Vet Pharmacol Ther, 2021 · Design: not stated · n: n = 5 · abstract only (PubMed) · open access (green)
    PMID 34658021DOI 10.1111/jvp.13026PMC11114070 (free full text)
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:This study determined plasma and tissue pharmacokinetics after oral CBD oil suspension administration in Hartley guinea pigs (Cavia porcellus), which spontaneously develop OA at 3 months of age.
    • Key findings · abstract:The area under the plasma concentration-versus-time curve was 379.5 and 873.7 h*ng/mL, maximum plasma concentration was 42 and 96.8 ng/mL, time to maximum plasma concentration was 1.6 and 4.8 h, and terminal phase half-life was 8.1 and 10.8 h for the 25 and 50 mg/kg doses, respectively.
    • AUC · abstract:The area under the plasma concentration-versus-time curve was 379.5 and 873.7 h*ng/mL, maximum plasma concentration was 42 and 96.8 ng/mL, time to maximum plasma concentration was 1.6 and 4.8 h, and terminal phase half-life was 8.1 and 10.8 h for the 25 and 50 mg/kg doses, respectively.
76. PigCannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers.
    Drug Dev Ind Pharm, 2010 · Design: not stated · abstract only (PubMed) · closed/paywalled
    PMID 20545522DOI 10.3109/03639041003657295
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:RESULTS: CBD was absorbed intranasally within 10 minutes with a bioavailability of 34-46%, except with 100% polyethylene glycol formulation in rats.
    • Key findings · abstract:The steady-state plasma concentration of CBD in guinea pigs after transdermal gel application was 6.3 +/- 2.1 ng/mL, which was attained at 15.5 +/- 11.7 hours.
    • Key findings · abstract:The steady-state concentration increased by 3.7-fold in the presence of enhancer.
    • Relative bioavailability · abstract:The steady-state concentration increased by 3.7-fold in the presence of enhancer.
    • Fractional absorption · abstract:RESULTS: CBD was absorbed intranasally within 10 minutes with a bioavailability of 34-46%, except with 100% polyethylene glycol formulation in rats.
77. RodentPharmacokinetics of Cannabidiol in Rat Brain Tissue After Single-Dose Administration of Different Formulations.
    Molecules, 2025 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 40649195DOI 10.3390/molecules30132676PMC12250628 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Cmax · full text, Table 2:Average values for the maximum concentration (Cmax), time to reach the maximum concentration (Tmax), and the area under the curve from 0 to 6 h (AUC0–6) of CBD (cannabidiol) and its metabolites in rat brain tissue after a single oral dose of 10 mg/kg CBD in different nanoformulations. Carrier A: CBD
    • Cmax · full text, Section '2.4. Transfer of CBD into the Brain of E':The following CBD pharmacokinetic parameters (PK) were then assessed: the maximum brain concentration (Cmax) over time (up to 6 h after CBD administration), the time needed to reach maximum concentration (Tmax) in brain tissue, and biotransformation.
    • Cmax · full text, Section '2.4.1. Pharmacokinetic Findings of CBD':Figure 4 shows a rapid increase in CBD in brain tissue for all tested carriers; the maximum concentration, Cmax, was reached within 1–2 h (Tmax) after gavage administration; then, a slower decrease occurred until 4 h, and no notable changes were observed between 4 h and 6 h.
    • Tmax · full text, Table 2:Average values for the maximum concentration (Cmax), time to reach the maximum concentration (Tmax), and the area under the curve from 0 to 6 h (AUC0–6) of CBD (cannabidiol) and its metabolites in rat brain tissue after a single oral dose of 10 mg/kg CBD in different nanoformulations. Carrier A: CBD powder; Carrier B: 10% CBD oil; Carrier C: SEDD
    • Tmax · full text, Section '2.4. Transfer of CBD into the Brain of E':The following CBD pharmacokinetic parameters (PK) were then assessed: the maximum brain concentration (Cmax) over time (up to 6 h after CBD administration), the time needed to reach maximum concentration (Tmax) in brain tissue, and biotransformation.
    • Tmax · full text, Section '2.4.1. Pharmacokinetic Findings of CBD':Figure 4 shows a rapid increase in CBD in brain tissue for all tested carriers; the maximum concentration, Cmax, was reached within 1–2 h (Tmax) after gavage administration; then, a slower decrease occurred until 4 h, and no notable changes were observed between 4 h and 6 h.
    • AUC · full text, Table 2:Average values for the maximum concentration (Cmax), time to reach the maximum concentration (Tmax), and the area under the curve from 0 to 6 h (AUC0–6) of CBD (cannabidiol) and its metabolites in rat brain tissue after a single oral dose of 10 mg/kg CBD in different nanoformulations. Carrier A: CBD powder; Carrier B: 10% CBD oil; Carrier C: SEDDS (self-emulsifying drug
    • AUC · full text, Section '2.4. Transfer of CBD into the Brain of E':The area under the curve (AUC0–6) illustrating changes in CBD concentration in brain tissue over 6 h period was used to assess the total animal’s body exposure by CBD (linear trapezoidal rule from time 0 to time of the last quantifiable concentration employed for area calculation [29]).
    • AUC · full text, Section '2.4.1. Pharmacokinetic Findings of CBD':In this case, the highest AUC0–6 (596 µg/kg × h) was calculated, indicating the highest exposure of brain tissue by CBD.
    • Form comparison · full text, Section '2.4.1. Pharmacokinetic Findings of CBD':In summary, carriers A, D, E, and F showed a slower decrease in CBD concentration over time compared to carriers B (10% CBD oil) and C (SEDDS with MCT oil) which might be desirable for therapeutic purposes.
    • Form comparison · full text, Section '2.4.1. Pharmacokinetic Findings of CBD':Higher Cmax (226 ± 118 µg/kg) was achieved by carrier C (SEDDS with MCT oil) compared to carrier D (SEDDS with sesame oil) for which the Cmax was 124 ± 45 µg/kg.
    • Form comparison · full text, Section '2.4.2. Pharmacokinetic Findings of CBD M':For carrier B, the Tmax of 7-COOH-CBD was delayed to 2 h, whereas for carrier F, it was substantially prolonged to 6 h, compared to 2 h for CBD.
78. RodentThe Impact of Cannabidiol (CBD) on Lipid Absorption and Lymphatic Transport in Rats.
    Nutrients, 2025 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 40292467DOI 10.3390/nu17061034PMC11944757 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Food effect · full text, Section '2.4. Lymph Collection':After overnight recovery, fasting lymph was collected and kept on ice for 1 h prior to lipid infusion.
    • Food effect · full text, Section '2.7. Measurements of Apolipoproteins':Fold changes in the lymphatic apolipoprotein output, including ApoA1, ApoA4, and ApoB48, were determined by normalizing the relative lymph apolipoprotein levels at each hourly time point to their respective baseline (0 h, fasting) levels.
    • Form comparison · full text, Section '3.2. Lymphatic Isotope Labeled TG and CH':At the 4th hour, the hourly lymphatic TG output peaked at ~51% recovery of the infused [3H]-TG in the high-dose CBD group, compared to 45% in the low-dose group and 37% in the vehicle group (p < 0.05, Figure 2a).
79. RodentThe Effect of Route of Administration and Vehicle on the Pharmacokinetics of THC and CBD in Adult, Neonate, and Breastfed Sprague-Dawley Rats.
    Cannabis Cannabinoid Res, 2024 · Design: not stated · abstract only (PubMed) · open access (green)
    PMID 37852006DOI 10.1089/can.2023.0121
    Verification: abstract-only auto-extract; unverified
80. RodentAbsorption and Bioavailability of Novel UltraShear Nanoemulsion of Cannabidiol in Rats.
    Med Cannabis Cannabinoids, 2023 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 37942295DOI 10.1159/000534473PMC10629855 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:RESULTS: Bioavailability of orally delivered CBD UltraShear nanoemulsion was calculated to be 18.6% at 6 h and 25.4% at 24 h.
    • Key findings · abstract:While oral-GI bioavailability is unsurprisingly limited by first-pass metabolism, it is nonetheless notable that CBD bioavailability for oral-GI UltraShear nanoemulsion CBD is roughly 3-4x higher than the typical bioavailability for oral-GI CBD delivered in oil solution or conventional edible formats.
    • Key findings · abstract:CONCLUSION: This study has provided a compelling demonstration of unprecedented speed and efficiency of oral-GI CBD absorption of CBD UltraShear nanoemulsions, achievi[excerpt truncated in our database — see source]
    • AUC · full text, Table 5.:Area under curve (AUC) calculations of oral CBD UltraShear nanoemulsion 5 mg/rat results at 6 h CBD AUC Relative bioavailability, % CBD-7-COOH (CBD equivalents) AUC 7-OH-CBD (CBD equivalents) AUC Total CBD equivalents AUC Relative total absorption, % Rat 1 621.8 20.60 2
    • AUC · full text, Table 8.:Area under curve (AUC) calculations of IV CBD Control 1 mg/rat results at 24 h CBD AUC Dose-adjusted (5X) CBD AUC CBD-7-COOH (CBD equivalents) AUC 7-OH-CBD (CBD equivalents) AUC Total CBD equivalents AUC Dose-adjusted (5X) total CBD equivalents AUC Rat 5 560.0 2,799.8 6
    • AUC · full text, Table 7.:Area under curve (AUC) calculations of oral CBD UltraShear Nanoemulsion 5 mg/rat results at 24 h CBD AUC Relative bioavailability, % CBD-7-COOH (CBD equivalents) AUC 7-OH-CBD (CBD equivalents) AUC TOTAL CBD equivalents AUC Relative total absorption, % Rat 1 1,073.9 27.9
    • Relative bioavailability · full text, Table 5.:Area under curve (AUC) calculations of oral CBD UltraShear nanoemulsion 5 mg/rat results at 6 h CBD AUC Relative bioavailability, % CBD-7-COOH (CBD equivalents) AUC 7-OH-CBD (CBD equivalents) AUC Total CBD equivalents AUC Relative total absorption, % Rat 1 621.8 20.60 2,917.9 230.8 3,770.4 57.90 Rat 2 326.8 10.80 1,698.8 89.5 2,115.1 32.50 Rat 3 460.1 15.20 2,128.8 133.2
    • Relative bioavailability · full text, Table 7.:Area under curve (AUC) calculations of oral CBD UltraShear Nanoemulsion 5 mg/rat results at 24 h CBD AUC Relative bioavailability, % CBD-7-COOH (CBD equivalents) AUC 7-OH-CBD (CBD equivalents) AUC TOTAL CBD equivalents AUC Relative total absorption, % Rat 1 1,073.9 27.9 4,964.0 474.0 6,512.0 83.4 Rat 2 657.9 17.1 4,105.7 256.7 5,020.3 64.3 Rat 3 584.5 15.2 6,254.0 321.5 7
    • Form comparison · full text, Table 3.:Time versus plasma concentration (ng/mL) of CBD and metabolites, CBD-7-COOH and 7-OH-CBD, after oral administration of 5 mg CBD nanoemulsion Rat 1 Rat 2 Rat 3 Rat 4 CBD CBD-7-COOH 7-OH-CBD CBD CBD-7-COOH 7-OH-CBD CBD CBD-7-COOH 7-OH-CBD CBD CBD-7-COOH 7-OH-CBD
    • Form comparison · full text, Table 4.:Time versus plasma concentrations (ng/mL) profile of CBD and metabolites, CBD-7-COOH and 7-OH-CBD, in plasma after IV administration of 1 mg control CBD Time Rat 5 Rat 6 Rat 7 CBD CBD-7-COOH 7-OH-CBD CBD CBD-7-COOH 7-OH-CBD CBD CBD-7-COOH 7-OH-CBD 0 min BLQ BLQ
81. RodentPharmacokinetics of Cannabidiol in Sprague-Dawley Rats After Oral and Pulmonary Administration.
    Cannabis Cannabinoid Res, 2023 · Design: not stated · abstract only (PubMed) · closed/paywalled
    PMID 36301522DOI 10.1089/can.2022.0121
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Methods: Pharmacokinetics, brain distribution, and urinary elimination of CBD and its major metabolites (6-hydroxy-cannabidiol [6-OH-CBD], 7-hydroxy-cannabidiol [7-OH-CBD], 7-carboxy-cannabidiol [7-COOH-CBD], and CBD-glucuronide) were evaluated in adult Sprague-Dawley rats following a single oral CBD ingestion (10 mg/kg in medium chain triglyceride oil; 24 male animals), and 1 or 14 days of repeated inhalation (0.9-13.9 mg/kg in propylene glycol [41%/59% by weight]; 5 male and 5 female animals per dose).
    • Key findings · abstract:Results: CBD was more rapidly absorbed following inhalation than ingestion (Tmax=5 min a[excerpt truncated in our database — see source]
    • Cmax · abstract:CBD Cmax was 24-fold higher following the highest pulmonary dose (13.9 mg/kg) versus an oral dose of comparable concentration (10 mg/kg).
    • Cmax · abstract:Cmax and AUClast (0-16 h) trended higher following repeated exposure.
    • Tmax · abstract:Results: CBD was more rapidly absorbed following inhalation than ingestion (Tmax=5 min and 2 h, respectively).
    • AUC · abstract:Cmax and AUClast (0-16 h) trended higher following repeated exposure.
    • AUC · abstract:While metabolites were detectable in plasma, AUClast (0-2 h) was at least 10- (7-OH-CBD, 7-COOH-CBD) to 100- (6-OH-CBD) fold lower than the parent compound.
    • AUC · abstract:AUClast (0-16 h) was ∼1.8-, ∼1.4-, and ∼2.4-fold higher following 14 days of exposure for 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD, respectively.
    • Relative bioavailability · abstract:CBD Cmax was 24-fold higher following the highest pulmonary dose (13.9 mg/kg) versus an oral dose of comparable concentration (10 mg/kg).
    • Relative bioavailability · abstract:While metabolites were detectable in plasma, AUClast (0-2 h) was at least 10- (7-OH-CBD, 7-COOH-CBD) to 100- (6-OH-CBD) fold lower than the parent compound.
    • Relative bioavailability · abstract:AUClast (0-16 h) was ∼1.8-, ∼1.4-, and ∼2.4-fold higher following 14 days of exposure for 6-OH-CBD, 7-OH-CBD, and 7-COOH-CBD, respectively.
    • Fractional absorption · abstract:Results: CBD was more rapidly absorbed following inhalation than ingestion (Tmax=5 min and 2 h, respectively).
82. RodentCannabidiol Produces Distinct U-Shaped Dose-Response Effects on Cocaine-Induced Conditioned Place Preference and Associated Recruitment of Prelimbic Neurons in Male Rats.
    Biol Psychiatry Glob Open Sci, 2022 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 35252951DOI 10.1016/j.bpsgos.2021.06.014PMC8896771 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Form comparison · full text, Section 'CBD Reduces CPP-Associated Neuronal Acti':Compared with vehicle, 7.5 mg/kg CBD significantly decreased Fos protein expression in the PL but not the IL, NAcc, or NAcs (Figure 3).
    • Form comparison · full text, Section 'CBD Produces Decreases in Neuronal Activ':To establish whether the observed reduction of PL neuronal activity by the behaviorally effective CBD dose (7.5 mg/kg) is selective for excitatory versus inhibitory neurons, in situ hybridization (RNAscope) was employed to quantify Vglut-mRNA-expressing, Vgat-mRNA-expressing, and Chat-mRNA-expressing neuronal subtypes (Figures 5 and 6).
83. RodentMaternal and Fetal Pharmacokinetic Analysis of Cannabidiol during Pregnancy in Mice.
    Drug Metab Dispos, 2021 · Design: not stated · abstract only (PubMed) · open access (bronze)
    PMID 33531413DOI 10.1124/dmd.120.000270
    Verification: abstract-only auto-extract; unverified
84. RodentAnticonvulsive Effects and Pharmacokinetic Profile of Cannabidiol (CBD) in the Pentylenetetrazol (PTZ) or N-Methyl-D-Aspartate (NMDA) Models of Seizures in Infantile Rats.
    Int J Mol Sci, 2021 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 35008517DOI 10.3390/ijms23010094PMC8744811 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:Plasma and brain levels of CBD were determined up to 24 h after administration.
    • AUC · full text, Section '2.1. Serum and Brain Levels of CBD':After administration of CBD 10 mg/kg the peak concentration in serum (1655 ± 664 ng/mL as detected using AUC) was reached at the interval 0.5 h and in the brain (996 ± 128 ng/g) at the 1 h interval.
    • Form comparison · full text, Section '2.1. Serum and Brain Levels of CBD':Concentration of CBD was significantly higher in the brain tissue compared to serum 1 h (p = 0.0352) and 24 h (p < 0.0001) after drug administration.
    • Form comparison · full text, Section '2.2. Effects of CBD on PTZ-Induced Seizu':Animals treated with CBD 60 mg/kg displayed reduced seizure severity compared to both controls (p < 0.0001) and CBD 10 mg/kg group (p = 0.0013) (Figure 2A).
    • Form comparison · full text, Section '2.4.1. Bar Holding Test':Administration of CBD resulted in significant shortening of time spent on the bar compared to controls in the 3rd test, i.e., 24 h after administration a dose of 10 mg/kg (p = 0.0029) as well as 60 mg/kg (p = 0.0102).
85. RodentUsing the Absorption Cocktail Approach to Assess Differential Absorption Kinetics of Cannabidiol Administered in Lipid-Based Vehicles in Rats.
    Mol Pharm, 2020 · Design: not stated · abstract only (PubMed) · closed/paywalled
    PMID 32352800DOI 10.1021/acs.molpharmaceut.0c00141
    Verification: abstract-only auto-extract; unverified
86. RodentInvestigation of cannabidiol gastro retentive tablets based on regional absorption of cannabinoids in rats.
    Eur J Pharm Biopharm, 2020 · Design: not stated · abstract only (PubMed) · closed/paywalled
    PMID 32422168DOI 10.1016/j.ejpb.2020.05.010
    Verification: abstract-only auto-extract; unverified
87. RodentPharmacokinetics of oral and intravenous cannabidiol and its antidepressant-like effects in chronic mild stress mouse model.
    Environ Toxicol Pharmacol, 2019 · Design: not stated · abstract only (PubMed) · closed/paywalled
    PMID 31173966DOI 10.1016/j.etap.2019.103202
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:A single bolus intravenous injection of CBD resulted in a half-life of 3.9 h, mean residence time of 3.3 h, and oral bioavailability of about 8.6%.
88. RodentAcute effect of cannabidiol on the activity of various novel antiepileptic drugs in the maximal electroshock- and 6 Hz-induced seizures in mice: Pharmacodynamic and pharmacokinetic studies.
    Neuropharmacology, 2019 · Design: not stated · abstract only (PubMed) · open access (green)
    PMID 31377197DOI 10.1016/j.neuropharm.2019.107733
    Verification: abstract-only auto-extract; unverified
89. RodentSimultaneous quantification of cannabinoids tetrahydrocannabinol, cannabidiol and CB1 receptor antagonist in rat plasma: An application to characterize pharmacokinetics after passive cannabis smoke inhalation and co-administration of rimonabant.
    J Pharm Biomed Anal, 2018 · Design: not stated · abstract only (PubMed) · not checked (off-topic)
    PMID 30077950DOI 10.1016/j.jpba.2018.07.004PMC6397651 (free full text)
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Maximum concentration (Cmax) for THC was observed immediately after rats were removed from the exposure chamber (10 min post completion) which declined with a terminal half-life of 3.7 h and clearance was calculated to be 1.1 (L/h).
    • Key findings · abstract:Rimonabant (i.p) at a dose of 3 mg/kg was rapidly absorbed and maximum concentration (Cmax) was seen at 11 min which declined with a terminal half-life of 5.4 h and clearance was calculated to be 2.0 (L/h).
    • Key findings · abstract:Exposure AUCinf (h* μg/L) for THC and rimonabant were 13.9 and 457.6 respectively.
    • Key findings · abstract:As this method was highly sensitive and required only 50 μL of plasma,[excerpt truncated in our database — see source]
    • Cmax · abstract:Maximum concentration (Cmax) for THC was observed immediately after rats were removed from the exposure chamber (10 min post completion) which declined with a terminal half-life of 3.7 h and clearance was calculated to be 1.1 (L/h).
    • Cmax · abstract:Rimonabant (i.p) at a dose of 3 mg/kg was rapidly absorbed and maximum concentration (Cmax) was seen at 11 min which declined with a terminal half-life of 5.4 h and clearance was calculated to be 2.0 (L/h).
    • AUC · abstract:Exposure AUCinf (h* μg/L) for THC and rimonabant were 13.9 and 457.6 respectively.
    • Fractional absorption · abstract:Rimonabant (i.p) at a dose of 3 mg/kg was rapidly absorbed and maximum concentration (Cmax) was seen at 11 min which declined with a terminal half-life of 5.4 h and clearance was calculated to be 2.0 (L/h).
90. RodentThe effect of Pro NanoLipospheres (PNL) formulation containing natural absorption enhancers on the oral bioavailability of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) in a rat model.
    Eur J Pharm Sci, 2017 · Design: not stated · abstract only (PubMed) · not checked (off-topic)
    PMID 28736128DOI 10.1016/j.ejps.2017.07.003
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Both molecules are poorly water soluble and subjected to extensive first pass metabolism in the gastrointestinal tract, leading to a limited oral bioavailability of approximately 9%.
    • Key findings · abstract:Oral administration of CBD-piperine-PNL resulted in 6-fold increase in AUC compared to CBD solution, proving to be the most effective of the screened formulations.
    • Key findings · abstract:The same trend was found in pharmacokinetic experiments of THC-piperine-PNL which resulted in a 9.3-fold increase in AUC as compared to THC solution.
    • AUC · abstract:Oral administration of CBD-piperine-PNL resulted in 6-fold increase in AUC compared to CBD solution, proving to be the most effective of the screened formulations.
    • AUC · abstract:The same trend was found in pharmacokinetic experiments of THC-piperine-PNL which resulted in a 9.3-fold increase in AUC as compared to THC solution.
    • Relative bioavailability · abstract:Oral administration of CBD-piperine-PNL resulted in 6-fold increase in AUC compared to CBD solution, proving to be the most effective of the screened formulations.
    • Relative bioavailability · abstract:The same trend was found in pharmacokinetic experiments of THC-piperine-PNL which resulted in a 9.3-fold increase in AUC as compared to THC solution.
91. RodentPharmacokinetic and behavioural profile of THC, CBD, and THC+CBD combination after pulmonary, oral, and subcutaneous administration in rats and confirmation of conversion in vivo of CBD to THC.
    Eur Neuropsychopharmacol, 2017 · Design: not stated · abstract only (PubMed) · closed/paywalled
    PMID 29129557DOI 10.1016/j.euroneuro.2017.10.037
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Concentrations of THC, its metabolites 11-OH-THC and THC-COOH, and CBD in serum and brain were determined over 24h, locomotor activity (open field) and sensorimotor gating (prepulse inhibition, PPI) were also evaluated.
92. RodentABC transporters P-gp and Bcrp do not limit the brain uptake of the novel antipsychotic and anticonvulsant drug cannabidiol in mice.
    PeerJ, 2016 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 27257556DOI 10.7717/peerj.2081PMC4888295 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:P-gp knockout (Abcb1a/b (-∕-)), Bcrp knockout (Abcg2 (-∕-)), combined P-gp/Bcrp knockout (Abcb1a/b (-∕-) Abcg2 (-∕-)) and WT mice were injected with CBD, before brain and plasma samples were collected at various time-points.
    • Key findings · abstract:In comparison, the brain/plasma concentration ratios of risperidone and 9-hydroxy risperidone were profoundly higher in P-gp knockout mice than WT mice.
    • Form comparison · full text, Section 'P-gp or Bcrp knockout did not increase b':Tukey’s post-hoc comparisons confirmed that no significant differences were observed between WT when individually compared to P-gp knockout, Bcrp knockout or P-gp/Bcrp knockout mice at 1, 2 or 3 h time-points.
    • Form comparison · full text, Section 'P-gp or Bcrp knockout did not influence ':P-gp/Bcrp knockout mice achieved a significantly higher brain/plasma concentration ratio for 9-hydroxy risperidone than WT mice at 1 h, however P-gp knockout mice failed to reach significance when compared to WT mice at this timepoint.
93. RodentPlasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), Δ⁹-tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive-compulsive behaviour.
    Psychopharmacology (Berl), 2012 · Design: not stated · abstract only (PubMed) · closed/paywalled
    PMID 21796370DOI 10.1007/s00213-011-2415-0
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:In rats, oral administration offered higher brain concentrations for CBD (120 mg/kg) and CBDV (60 mg/kg), but not for Δ(9)-THCV (30 mg/kg) and CBG (120 mg/kg), for which the intraperitoneal route was more effective.
94. Other animalA microfluidic and mechanistic modeling approach to enhance oral bioavailability of cannabidiol via poloxamer-coated camel milk exosomes.
    Int J Pharm, 2026 · Design: not stated · abstract only (PubMed) · closed/paywalled
    PMID 42641999DOI 10.1016/j.ijpharm.2026.127347
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:In MDCK monolayers, CBD-CMDE-P407 showed higher apparent permeability than the control formulation, with a Papp of 29.56 × 10-6 ± 0.78 cm/s.
    • Key findings · abstract:Following oral administration in rats, CBD-CMDE-P407 increased systemic CBD exposure compared with the control formulation, with Cmax of 719.58 ± 27.63 ng/mL and AUC0-24 h of 2947.88 ± 124.03 h·ng/mL.
    • Cmax · abstract:Following oral administration in rats, CBD-CMDE-P407 increased systemic CBD exposure compared with the control formulation, with Cmax of 719.58 ± 27.63 ng/mL and AUC0-24 h of 2947.88 ± 124.03 h·ng/mL.
    • AUC · abstract:Following oral administration in rats, CBD-CMDE-P407 increased systemic CBD exposure compared with the control formulation, with Cmax of 719.58 ± 27.63 ng/mL and AUC0-24 h of 2947.88 ± 124.03 h·ng/mL.
95. Other animalPharmacokinetic studies and synergistic antitumor effects of cannabichromene and cannabidiol in drug-resistant breast cancers.
    Drug Deliv Transl Res, 2026 · Design: not stated · abstract only (PubMed) · closed/paywalled
    PMID 41670942DOI 10.1007/s13346-026-02057-1
    Verification: abstract-only auto-extract; unverified
96. Other animalPharmacokinetics and tolerability of liposomal synthetic cannabidiol subcutaneous depot in Holstein dairy calves.
    J Dairy Sci, 2026 · Design: not stated · abstract only (PubMed) · open access (gold)
    PMID 41349822DOI 10.3168/jds.2025-27373
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Blood was sampled for CBD and its metabolites, complete blood count, serum chemistry and serum amyloid A up to 6 wk.
    • Key findings · abstract:Plasma CBD concentrations were detected up to a median of 4.5 wk; with median peak plasma concentration (Cmax) 44.1 ng/mL, median time to Cmax 1 d and median half-life 5.3 d.
    • Key findings · abstract:The primary metabolite, 7-carboxy-CBD, exceeded CBD exposure by 9-fold (4-16) based on the area under the curve.
    • Cmax · abstract:Plasma CBD concentrations were detected up to a median of 4.5 wk; with median peak plasma concentration (Cmax) 44.1 ng/mL, median time to Cmax 1 d and median half-life 5.3 d.
    • AUC · abstract:The primary metabolite, 7-carboxy-CBD, exceeded CBD exposure by 9-fold (4-16) based on the area under the curve.
    • Relative bioavailability · abstract:The primary metabolite, 7-carboxy-CBD, exceeded CBD exposure by 9-fold (4-16) based on the area under the curve.
97. Other animalComparative Study on Cannabidiol-Loaded Solubilizing Systems for Improvement of Oral Bioavailability: Liposome and Cyclodextrin-Based Formulations.
    Biopharm Drug Dispos, 2026 · Design: not stated · abstract only (PubMed) · closed/paywalled
    PMID 41454837DOI 10.1002/bdd.70019
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:In contrast, LIP/CBD significantly enhanced the dissolution of CBD, as evidenced by 8-fold higher dissolution amount than that of crystalline CBD.
    • Key findings · abstract:Orally administered LIP/CBD and CD/CBD exhibited significant improvements of oral absorption with 22- and 5.3-fold higher systemic exposure, respectively.
    • Relative bioavailability · abstract:In contrast, LIP/CBD significantly enhanced the dissolution of CBD, as evidenced by 8-fold higher dissolution amount than that of crystalline CBD.
    • Relative bioavailability · abstract:Orally administered LIP/CBD and CD/CBD exhibited significant improvements of oral absorption with 22- and 5.3-fold higher systemic exposure, respectively.
98. Other animalPharmacokinetics of Buccally Administered Cannabidiol and Oral Carprofen During Single- and Repeated-Dose Administration in Dogs.
    J Vet Pharmacol Ther, 2026 · Design: not stated · abstract only (PubMed) · open access (hybrid)
    PMID 42813543DOI 10.1111/jvp.70114
    Verification: abstract-only auto-extract; unverified
    • Key findings · abstract:Plasma samples were collected during the first 12 h after the initial dose and at two and 4 weeks of treatment.
    • Key findings · abstract:Among metabolites, 7-COOH-CBD showed greater exposure and persistence than 7-OH-CBD.
99. Other animalPharmacokinetic Modeling of the "Nose-to-Brain" Pathway as Demonstrated by Intranasal Administration of Cannabidiol-Loaded Nanoparticles.
    Pharmaceuticals (Basel), 2026 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
    PMID 41901301DOI 10.3390/ph19030456PMC13029557 (free full text)
    Verification: full-text auto-extracted verbatim snippets with location; needs human check
    • Key findings · abstract:Results: Intranasal administration resulted in a bioavailability of 47.9%.
    • Key findings · abstract:Systemic absorption accounted for 44% of the absorbed drug, while 56% was absorbed by direct brain entry.
    • Key findings · abstract:Intranasal administration resulted in rapid brain penetration with a brain tmax of 10 min and demonstrated a brain bioavailability of 28.5% compared to bioavailability after intravenous bolus injection of cannabidiol solution.
    • Tmax · abstract:Intranasal administration resulted in rapid brain penetration with a brain tmax of 10 min and demonstrated a brain bioavailability of 28.5% compared to bioavailability after intravenous bolus injection of cannabidiol solution.
    • Fractional absorption · abstract:Systemic absorption accounted for 44% of the absorbed drug, while 56% was absorbed by direct brain entry.
    • AUC · full text, Table 2:18.0 λ1, min−1 0.1286 0.1051 λ2, min−1 0.0031 0.0028 t1/2 λ2, min 222.8 245.9 Ka, min−1 --- 0.1112 t1/2 Ka, min --- 6.23 V1, mL 276 --- AUC0–∞, ng ⸳ min/mL 13,185.3 6844.3 F , % 100 47.9 K10, min−1 0.0275 --- K12, min−1 0.0897 --- K21, min−1 0.0146 --- K12(IN), min−1 --- 0.0697 K21(IN), min−1 --- 0.0107 Ka1, min−1 --- 0.0489 (44%) Ka2, min−1 --- 0.0623 (56%)
    • Form comparison · full text, Section '4. Conclusions':The present pharmacokinetic study showed that the absolute bioavailability of CBD after intranasal administration was relatively high, 47.9%, followed by a significantly lower systemic exposure compared to IV injection of a similar dose.
100. Other animalMetabolic effects and pharmacokinetics of oral cannabidiol (CBD) in Connemara ponies following 21 days of treatment.
     Front Vet Sci, 2026 · Design: not stated · n: n = 7 · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 42221961DOI 10.3389/fvets.2026.1813917PMC13215832 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:Plasma CBD and metabolite concentrations were measurable, with Cmax increasing from 22.79 ± 13.24 ng/mL to 39.93 ± 14.45 ng/mL after the, tmax ranging from 3.14 ± 1.07 to 2.29 ± 0.76 h, and an accumulation ratio of 2.75 ± 1.51, indicating moderate accumulation.
     • Cmax · abstract:Plasma CBD and metabolite concentrations were measurable, with Cmax increasing from 22.79 ± 13.24 ng/mL to 39.93 ± 14.45 ng/mL after the, tmax ranging from 3.14 ± 1.07 to 2.29 ± 0.76 h, and an accumulation ratio of 2.75 ± 1.51, indicating moderate accumulation.
     • Tmax · abstract:Plasma CBD and metabolite concentrations were measurable, with Cmax increasing from 22.79 ± 13.24 ng/mL to 39.93 ± 14.45 ng/mL after the, tmax ranging from 3.14 ± 1.07 to 2.29 ± 0.76 h, and an accumulation ratio of 2.75 ± 1.51, indicating moderate accumulation.
     • Cmax · full text, Table 1:d last dose following oral administration of CBD at 2 mg/kg every 12 h. Parameter Dosing regimen After first dose (n = 7) After last dose (n = 7) CBD Cmax (ng/mL) 22.79 ± 13.24 39.93 ± 14.45* tmax (h) 3.14 ± 1.07 2.29 ± 0.76 ns t½ (elim) (h) 5.48 ± 2.06 4.41 ± 1.23 ns λz (1/h) 0.14 ± 0.05 0.18 ± 0.08 ns Vz/F (mL/kg) 156350.50 ± 117916.16 59966.30 ± 23267.52 ns Cl/F (mL/kg/h) 18384.77 ± 7379.70 918
     • Cmax · full text, Section 'Pharmacokinetics of CBD and its main met':After administration of the first dose of CBD, the Cmax of CBD was 22.79 ± 13.24 ng/mL, whereas by the end of the study, following the final dose, it had increased to 39.93 ± 14.45 ng/mL.
     • Tmax · full text, Table 1:of CBD at 2 mg/kg every 12 h. Parameter Dosing regimen After first dose (n = 7) After last dose (n = 7) CBD Cmax (ng/mL) 22.79 ± 13.24 39.93 ± 14.45* tmax (h) 3.14 ± 1.07 2.29 ± 0.76 ns t½ (elim) (h) 5.48 ± 2.06 4.41 ± 1.23 ns λz (1/h) 0.14 ± 0.05 0.18 ± 0.08 ns Vz/F (mL/kg) 156350.50 ± 117916.16 59966.30 ± 23267.52 ns Cl/F (mL/kg/h) 18384.77 ± 7379.70 9180.80 ± 1565.62** AUC0-τ (h*ng/mL) 101.15 ±
     • Tmax · full text, Section 'Pharmacokinetics of CBD and its main met':The tmax was 3.14 ± 1.07 h after the first dose and 2.29 ± 0.76 h after the last dose, while the t½ (elim) was 5.48 ± 2.06 h and 4.41 ± 1.23 h, respectively.
     • AUC · full text, Table 1:s λz (1/h) 0.14 ± 0.05 0.18 ± 0.08 ns Vz/F (mL/kg) 156350.50 ± 117916.16 59966.30 ± 23267.52 ns Cl/F (mL/kg/h) 18384.77 ± 7379.70 9180.80 ± 1565.62** AUC0-τ (h*ng/mL) 101.15 ± 47.97 223.12 ± 36.61*** AUC0-∞ (h*ng/mL) 123.37 ± 44.40 — AUC504-∞ (h*ng/mL) — 269.01 ± 31.29 AUC0-∞ or 504-∞ extrapolation (%) 21.02 ± 14.42 17.22 ± 8.03 ns MRT0-∞ (h) 8.68 ± 3.20 7.29 ± 1.58 ns Rac — 2.75 ± 1.51 7-OH-CBD C
     • Form comparison · full text, Section 'Blood insulin and glucose responses duri':Following the treatment period, insulin concentrations remained numerically higher in the CBD-treated group at 60 and 90 min (60.07 vs. 92.97 μIU/mL at 60 min; 54.45 vs. 91.57 μIU/mL at 90 min;
     • Form comparison · full text, Section 'Physical examination, body weight, BCS a':In geldings, mean heart rate decreased compared to pre-treatment values (24 h post-treatment: estimate ± SE = −5.33 ± 1.88, t = −2.844, p = 0.022; day 21: −6.67 ± 1.88, t = −3.556, p = 0.005;
     • Form comparison · full text, Section 'Blood hematology, biochemistry and ACTH ':Although total bilirubin concentrations remained within the reference range (7–60 μmol/L) at all time points in all ponies, the CBD-treated group showed significantly lower baseline values compared with controls (estimate ± SE = 5.668 ± 1.863 μmol/L, z = 3.043, p = 0.012).
101. Other animalComparative in vitro safety assessments of synthetized and plant-derived cannabidiol (CBD), and pharmacokinetics of synthetized CBD: evidence of similar toxicological profiles and accumulation upon repeated oral administration.
     Front Toxicol, 2026 · Design: not stated · abstract only (PubMed) · not checked (off-topic)
     PMID 42761342DOI 10.3389/ftox.2026.1844643PMC13586287 (free full text)
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:CBD and its metabolites (7-COOH-CBD, 7-OH-CBD, 6-OH-CBD) were measured in plasma and tissues using liquid chromatography-tandem mass spectrometry.
     • Key findings · abstract:Over 21 days, repeated dosing increased plasma CBD (AUCINF_D 567 vs. 209 h*kg*ng/mL/mg;[excerpt truncated in our database — see source]
     • Key findings · abstract:Day 21 vs. 1), 7-COOH-CBD (AUClast_D 1006 vs. 581), 6-OH-CBD (AUClast_D 33 vs. 13) and 7-OH-CBD (AUClast_D 43 vs. 31) exposure, and prolonged CBD half-life (41.9 h vs. 5.9 h).
     • Key findings · abstract:The steady-state plasma CBD concentration was achieved by Day 6.
     • Key findings · abstract:Tissue analysis showed marked CBD accumulation in adipose tissue (70,124 ng/g, 1470-fold relative to plasma level) a[excerpt truncated in our database — see source]
     • AUC · abstract:Over 21 days, repeated dosing increased plasma CBD (AUCINF_D 567 vs. 209 h*kg*ng/mL/mg;
     • AUC · abstract:Day 21 vs. 1), 7-COOH-CBD (AUClast_D 1006 vs. 581), 6-OH-CBD (AUClast_D 33 vs. 13) and 7-OH-CBD (AUClast_D 43 vs. 31) exposure, and prolonged CBD half-life (41.9 h vs. 5.9 h).
     • Relative bioavailability · abstract:Tissue analysis showed marked CBD accumulation in adipose tissue (70,124 ng/g, 1470-fold relative to plasma level) and mesenteric lymph nodes (10,018 ng/g, 201-fold relative to plasma level).
     • Relative bioavailability · abstract:Notably, 7-OH-CBD accumulated in adipose tissue (42 ng/g, 21-fold relative to plasma level) and mesenteric lymph nodes (136 ng/g, 73-fold relative to plasma level).
102. Other animalOil-based and oil-free formulations for enhancing cannabidiol bioavailability.
     J Cannabis Res, 2025 · Design: randomized; crossover · n: n = 75 · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 41331788DOI 10.1186/s42238-025-00371-yPMC12777474 (free full text)
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:Among emulsions, droplet size significantly influenced bioavailability: the 16 μm formulation yielded the highest exposure, with AUClast and Cmax values reaching 291% and 455% of the reference, respectively.
     • Key findings · abstract:Higher concentrations of Tween 20 accelerated absorption but reduced overall exposure, while an excess of lecithin decreased bioavailability.
     • Cmax · abstract:Among emulsions, droplet size significantly influenced bioavailability: the 16 μm formulation yielded the highest exposure, with AUClast and Cmax values reaching 291% and 455% of the reference, respectively.
     • AUC · abstract:Among emulsions, droplet size significantly influenced bioavailability: the 16 μm formulation yielded the highest exposure, with AUClast and Cmax values reaching 291% and 455% of the reference, respectively.
     • Cmax · full text, Section 'Oil type':Cmax, AUClast reference ratios are given as geometric means (± 90% CI).
     • Cmax · full text, Section 'Droplet size':These values are higher compared to those measured in our previous work (Jelínek et al. 2024) considering emulsion distribution was very polydisperse covering range from 10 to 100 μm, where the AUC and Cmax were 3811 ng/mL.h and 860 ng/mL, respectively, compared to those obtained in this work with AUC 4357 ng/mL.h and Cmax 888 ng/mL for the T3 formulation with narrow distribution.
     • Tmax · full text, Section 'Surfactant concentration':Formulation T7 without the addition of TW20 exhibited a significantly higher Cmax and a trend toward shortening Tmax by 1.94-fold, increasing the total exposure to the drug with a bioavailability of 202.8%.
     • AUC · full text, Section 'Oil type':Cmax, AUClast reference ratios are given as geometric means (± 90% CI).
     • AUC · full text, Section 'Droplet size':These values are higher compared to those measured in our previous work (Jelínek et al. 2024) considering emulsion distribution was very polydisperse covering range from 10 to 100 μm, where the AUC and Cmax were 3811 ng/mL.h and 860 ng/mL, respectively, compared to those obtained in this work with AUC 4357 ng/mL.h and Cmax 888 ng/mL for the T3 formulation with narrow distribution.
     • Relative bioavailability · full text, Section 'Surfactant concentration':Formulation T7 without the addition of TW20 exhibited a significantly higher Cmax and a trend toward shortening Tmax by 1.94-fold, increasing the total exposure to the drug with a bioavailability of 202.8%.
     • Food effect · full text, Section 'In vivo animal tests':Animals were fasted for 4 h before and after dosing with free access to water.
     • Form comparison · full text, Section 'Droplet size':These values are higher compared to those measured in our previous work (Jelínek et al. 2024) considering emulsion distribution was very polydisperse covering range from 10 to 100 μm, where the AUC and Cmax were 3811 ng/mL.h and 860 ng/mL, respectively, compared to those obtained in this work with AUC 4357 ng/mL.h and Cmax 888 ng/mL for the T3 formulation with narrow distribution.
     • Form comparison · full text, Section 'Droplet size':On the other hand, low bioavailability for submicron formulation (T5) at the level of 102.6% compared to the reference solution is surprising.
103. Other animalPharmacokinetics of a single oral administration of two cannabidiol formulations in fed and fasted horses.
     Front Vet Sci, 2025 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 40046423DOI 10.3389/fvets.2025.1515833PMC11880937 (free full text)PDF
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     • Cmax · full text, Table 2:.91) 7.76§ ± 3.63*(4.56–11.39)(a) 7.20§ ± 2.49*(4.39–10.11)(c) Tmax h 2.50 ± 2.51(0.25–8) 1.94 ± 0.56(1.50–3) 2.32 ± 2.34(0.25–6) 1.75 ± 1.25(0.25–4) Cmax ng/mL 12.12 ± 4.63(6.19–18.90) 17.35 ± 10.77(3.32–36.23) 22.91 ± 22.76(5.53–71.10) 14.18 ± 8.53(5.28–31.35) AUC 0-t ng/mL*h 80.55 ± 44.58(35.61–177.96) 88.72 ± 40.65(37.39–161.49) 68.81 ± 14.23(51.77–95.31) 81.15 ± 51.38(32.53–177.23) AUC 0-∞ ng
     • Cmax · full text, Section 'Results':In addition, little fluctuations in CBD plasma concentrations were sometimes observed in the terminal phase (between 8 and 10 h) of the concentration-time curves; these fluctuations were generally lower than 0.5 ng/mL, with only one fasted horse showing a secondary peak similar to the Cmax at 8 h following CBD oil administration.
     • Cmax · full text, Section 'Results':In fasted horses, Cmax was achieved between 1.50 and 3 h following CBD administration, while in fed horses Cmax was observed at the first sampling time (0.25 h) in two subjects and between 1.50 and 4 h in the remaining animals.
     • Tmax · full text, Table 2:d status Paste in fed status t1/2λz h 6.70§ ± 0.79*(5.58–7.77)(b) 8.36§ ± 1.59*(6.70–12.91) 7.76§ ± 3.63*(4.56–11.39)(a) 7.20§ ± 2.49*(4.39–10.11)(c) Tmax h 2.50 ± 2.51(0.25–8) 1.94 ± 0.56(1.50–3) 2.32 ± 2.34(0.25–6) 1.75 ± 1.25(0.25–4) Cmax ng/mL 12.12 ± 4.63(6.19–18.90) 17.35 ± 10.77(3.32–36.23) 22.91 ± 22.76(5.53–71.10) 14.18 ± 8.53(5.28–31.35) AUC 0-t ng/mL*h 80.55 ± 44.58(35.61–177.96) 88.72
     • AUC · full text, Table 2:2 ± 2.34(0.25–6) 1.75 ± 1.25(0.25–4) Cmax ng/mL 12.12 ± 4.63(6.19–18.90) 17.35 ± 10.77(3.32–36.23) 22.91 ± 22.76(5.53–71.10) 14.18 ± 8.53(5.28–31.35) AUC 0-t ng/mL*h 80.55 ± 44.58(35.61–177.96) 88.72 ± 40.65(37.39–161.49) 68.81 ± 14.23(51.77–95.31) 81.15 ± 51.38(32.53–177.23) AUC 0-∞ ng/mL*h 65.42 ± 17.77(40.21–89.19)(b) 100.46 ± 45.93(41.59–180.77) 80.53 ± 23.54(54.14–117.32)(a) 95.14 ± 56.58(37.
     • AUC · full text, Section 'Results':In two fed horses treated with CBD oil and one fed horse treated with the paste, the terminal phase obtained from the NCA was considered unreliable by virtue of an extrapolated AUC percentage greater than 46%.
     • Food effect · full text, Table 2:Main pharmacokinetic parameters obtained following oral administration of CBD oil or paste at 1 mg/kg in 8 horses both in fed and in fasted status (Data expressed as mean ± S.D. and range in brackets). PK Parameter CBD treatment Unit Oil in fasted status Paste in fasted status Oil in fed status Paste in fed status t1/2λz h 6.70§ ± 0.79*(5.58–7.77)(b) 8.36§ ± 1.59*(6.70–12
     • Food effect · full text, Section 'Animals and treatments':They were all fed polyphite hay at a rate of 2.5% of their body weight divided into three daily meals (at 07:00, 13:00 and 19:00), and water was available ad libitum.
     • Food effect · full text, Section 'Animals and treatments':All animals received both formulations 2 h before the morning meal, corresponding to 10 h after the previous meal (fasted status), and 1 h after (fed status).
     • Form comparison · full text, Section 'Blood sampling':Blood samples (10 mL) were taken from the jugular vein following the insertion of a catheter, before drug administration and at pre-fixed time-points during the 24 h following the CBD administration (0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10 and 24 h), to determine drug concentration vs time curves.
104. Other animalPharmacokinetic Characteristics of a Single Cannabidiol Dose in Oil and Treat Forms and Health Impacts After 30 Days of Administration in Dogs.
     Animals (Basel), 2025 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 40427347DOI 10.3390/ani15101470PMC12108255 (free full text)
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     • Key findings · abstract:The CBD-infused rice bran oil formulation (OG) achieved a significantly higher dose-normalized maximum plasma concentration (Cmax, 58.40 vs. 21.29 kg·ng/mL/mg) and area under the curve (AUC0-inf, 305.85 vs. 141.75 h·kg·ng/mL/mg) compared to the treats (TG).
     • Key findings · abstract:The treat formulation exhibited relative reductions in bioavailability, with AUC and Cmax values approximately 2.2- and 2.7-fold lower than the oil group.
     • Cmax · abstract:The CBD-infused rice bran oil formulation (OG) achieved a significantly higher dose-normalized maximum plasma concentration (Cmax, 58.40 vs. 21.29 kg·ng/mL/mg) and area under the curve (AUC0-inf, 305.85 vs. 141.75 h·kg·ng/mL/mg) compared to the treats (TG).
     • Cmax · abstract:The treat formulation exhibited relative reductions in bioavailability, with AUC and Cmax values approximately 2.2- and 2.7-fold lower than the oil group.
     • Tmax · abstract:The terminal half-life (~9.66 h OG vs. 8.52 h TG) and time to peak (2.38 h OG vs. 3.63 h TG) did not differ significantly.
     • AUC · abstract:The CBD-infused rice bran oil formulation (OG) achieved a significantly higher dose-normalized maximum plasma concentration (Cmax, 58.40 vs. 21.29 kg·ng/mL/mg) and area under the curve (AUC0-inf, 305.85 vs. 141.75 h·kg·ng/mL/mg) compared to the treats (TG).
     • AUC · abstract:The treat formulation exhibited relative reductions in bioavailability, with AUC and Cmax values approximately 2.2- and 2.7-fold lower than the oil group.
     • Relative bioavailability · abstract:The treat formulation exhibited relative reductions in bioavailability, with AUC and Cmax values approximately 2.2- and 2.7-fold lower than the oil group.
     • Cmax · full text, Table 1:PK parameters (mean ± SEM) of CBD following a single oral dose administration in the OG and TG groups, where p-values < 0.05. The dose-normalized Cmax and AUC parameters are presented. Parameter Unit OG (n = 8) TG (n = 8) p-Value HL_Lambda_z (T1/2) h   Mean ± SEM 9.66 ± 1.52 8.52 ± 1.15 0.7984   Range (Median) 4.87 - 15.1 (8.5) 1.8 12.75 (8.95)   95% CI 6.68 - 12.63 6.25 1
     • Tmax · full text, Table 1:Mean ± SEM 9.66 ± 1.52 8.52 ± 1.15 0.7984   Range (Median) 4.87 - 15.1 (8.5) 1.8 12.75 (8.95)   95% CI 6.68 - 12.63 6.25 10.78 Tmax h   Mean ± SEM 2.38 ± 0.26 3.63 ± 1.07 0.5793   Range (Median) 1 - 3 (2.5) 1 10 (3)   95% CI 1.85 - 2.89 1.53 5.71 Cmax_D kg*ng/mL/mg   Mean ± SEM 58.40 ± 8.24 21.29 ± 3.15 0.0011
     • Tmax · full text, Section '3. Results':The OG reached the Tmax faster than the TG (2.38 ± 0.26 h vs. 3.63 ± 1.07 h), although this difference was not statistically significant.
     • AUC · full text, Table 1:rameters (mean ± SEM) of CBD following a single oral dose administration in the OG and TG groups, where p-values < 0.05. The dose-normalized Cmax and AUC parameters are presented. Parameter Unit OG (n = 8) TG (n = 8) p-Value HL_Lambda_z (T1/2) h   Mean ± SEM 9.66 ± 1.52 8.52 ± 1.15 0.7984   Range (Median) 4.87 - 15.1 (8.5) 1.8 12.75 (8.95)   95% CI 6.68 - 12.63 6.25 10.78
     • AUC · full text, Section '3. Results':Relative bioavailability in the TG was markedly reduced, with values of 46.35% and 36.46% for AUC_D and Cmax_D, respectively.
     • AUC · full text, Section '3. Results':In addition, the TG showed a higher calculated inter-individual variation for AUCinf-D (95.97%) compared to the OG (69.23%), indicating greater variability in drug exposure among individuals in the TG.
     • Relative bioavailability · full text, Section '3. Results':Relative bioavailability in the TG was markedly reduced, with values of 46.35% and 36.46% for AUC_D and Cmax_D, respectively.
     • Form comparison · full text, Section '3. Results':In addition, the TG showed a higher calculated inter-individual variation for AUCinf-D (95.97%) compared to the OG (69.23%), indicating greater variability in drug exposure among individuals in the TG.
     • Form comparison · full text, Section '3. Results':The OG reached the Tmax faster than the TG (2.38 ± 0.26 h vs. 3.63 ± 1.07 h), although this difference was not statistically significant.
105. Other animalEnhancing Cannabidiol Bioavailability: Development and Evaluation of an Amorphous Cannabidiol Powder Formulation.
     J Nutr Sci Vitaminol (Tokyo), 2025 · Design: not stated · abstract (PubMed); full-text PDF saved · open access (gold)
     PMID 40887280DOI 10.3177/jnsv.71.312PDF
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     • Key findings · abstract:The Cmax values demonstrated a 3.9-fold increase for the amorphous CBD powder formulation containing polyvinylpyrrolidone (PVP) as a polymer (F3) and a 3.0-fold increase for the amorphous CBD powder formulation containing hydroxypropyl methylcellulose (HPMC) as a polymer (F4) compared to the CBD isolate powder.
     • Key findings · abstract:Furthermore, the AUC0-6h values for F3 and F4 were 5.3- and 5.2-fold higher than those for CBD isolate powder, respectively, indicating a significant enhancement.
     • Cmax · abstract:The Cmax values demonstrated a 3.9-fold increase for the amorphous CBD powder formulation containing polyvinylpyrrolidone (PVP) as a polymer (F3) and a 3.0-fold increase for the amorphous CBD powder formulation containing hydroxypropyl methylcellulose (HPMC) as a polymer (F4) compared to the CBD isolate powder.
     • Tmax · abstract:The Tmax values were also significantly shorter for F3 and F4, at 0.9±0.1 h and 0.8±0.1 h, respectively, compared to >6.0 h for CBD isolate powder.
     • AUC · abstract:Furthermore, the AUC0-6h values for F3 and F4 were 5.3- and 5.2-fold higher than those for CBD isolate powder, respectively, indicating a significant enhancement.
     • Relative bioavailability · abstract:The Cmax values demonstrated a 3.9-fold increase for the amorphous CBD powder formulation containing polyvinylpyrrolidone (PVP) as a polymer (F3) and a 3.0-fold increase for the amorphous CBD powder formulation containing hydroxypropyl methylcellulose (HPMC) as a polymer (F4) compared to the CBD isolate powder.
     • Relative bioavailability · abstract:Furthermore, the AUC0-6h values for F3 and F4 were 5.3- and 5.2-fold higher than those for CBD isolate powder, respectively, indicating a significant enhancement.
     • Cmax · full text, p.1:ey rats, we orally administered 10 mg/kg of CBD isolate powder with a crys- talline structure and our developed amorphous CBD powder formulation. The Cmax values demonstrated a 3.9-fold increase for the amorphous CBD powder formulation containing polyvinylpyrrolidone (PVP) as a polymer (F3) and a 3.0-fold increase for the amorphous CBD powder formulation containing hydroxypropyl methylcellulose (H
     • Cmax · full text, p.3:it is strongly inferred that there is no significant impact on the maximum plasma con- ronidase solution, and 30 mL of plasma sample were centration (Cmax), the area under the concentration– combined in a brown microtube. The CBD conjugate time curve (AUC), or the time to reach the maximum was hydrolyzed by incubating the mixture at 37˚C for plasma concentration (Tmax) compared to oral gavage 4 h,
     • Cmax · full text, p.4:in rats after oral administra- tion of Control and amorphous CBD powder formula- tions F1 and F2 (CBD dose 10 mg/kg). Control F1 F2 (n54) (n54) (n54) Cmax (ng/mL) 10.762.2 23.664.1 51.5618.8 AUC0–6h 30.069.8a 86.2612.1ab 160.7642.5b (ng/mL·h) Tmax (h) .5.560.5a 0.960.1b 1.060.0b Cmax, maximum plasma concentration; AUC0–6h, area Fig. 2. X-ray diffraction patterns of (I) cannabidiol under the plasma
     • Tmax · full text, p.1:AUC0–6h values for F3 and F4 were 5.3- and 5.2-fold higher than those for CBD isolate powder, respectively, indicating a significant enhancement. The Tmax values were also significantly shorter for F3 and F4, at 0.960.1 h and 0.860.1 h, respectively, compared to .6.0 h for CBD isolate powder. These findings demonstrate the superior BA of the amorphous CBD formulation. Based on these results, the a
     • Tmax · full text, p.3:tube. The CBD conjugate time curve (AUC), or the time to reach the maximum was hydrolyzed by incubating the mixture at 37˚C for plasma concentration (Tmax) compared to oral gavage 4 h, Then, 15 mL of methanol with phenprocoumon administration. Based on the previously established (500 ng/mL) as an internal standard and 0.5 mL of a average body weight of 260 g, approximately 10 mg 1 : 1 mixture of e
     • Tmax · full text, p.4:F2 (CBD dose 10 mg/kg). Control F1 F2 (n54) (n54) (n54) Cmax (ng/mL) 10.762.2 23.664.1 51.5618.8 AUC0–6h 30.069.8a 86.2612.1ab 160.7642.5b (ng/mL·h) Tmax (h) .5.560.5a 0.960.1b 1.060.0b Cmax, maximum plasma concentration; AUC0–6h, area Fig. 2. X-ray diffraction patterns of (I) cannabidiol under the plasma concentration–time curve; Tmax, time (CBD) isolate powder; (II) physical mixture (F1); (III)
     • AUC · full text, p.1:orphous CBD powder formulation containing hydroxypropyl methylcellulose (HPMC) as a polymer (F4) compared to the CBD isolate powder. Furthermore, the AUC0–6h values for F3 and F4 were 5.3- and 5.2-fold higher than those for CBD isolate powder, respectively, indicating a significant enhancement. The Tmax values were also significantly shorter for F3 and F4, at 0.960.1 h and 0.860.1 h, respectively,
     • AUC · full text, p.3:gly inferred that there is no significant impact on the maximum plasma con- ronidase solution, and 30 mL of plasma sample were centration (Cmax), the area under the concentration– combined in a brown microtube. The CBD conjugate time curve (AUC), or the time to reach the maximum was hydrolyzed by incubating the mixture at 37˚C for plasma concentration (Tmax) compared to oral gavage 4 h, Then, 15 m
     • AUC · full text, p.4:ntrol and amorphous CBD powder formula- tions F1 and F2 (CBD dose 10 mg/kg). Control F1 F2 (n54) (n54) (n54) Cmax (ng/mL) 10.762.2 23.664.1 51.5618.8 AUC0–6h 30.069.8a 86.2612.1ab 160.7642.5b (ng/mL·h) Tmax (h) .5.560.5a 0.960.1b 1.060.0b Cmax, maximum plasma concentration; AUC0–6h, area Fig. 2. X-ray diffraction patterns of (I) cannabidiol under the plasma concentration–time curve; Tmax, time (CB
     • Relative bioavailability · full text, p.1:ered 10 mg/kg of CBD isolate powder with a crys- talline structure and our developed amorphous CBD powder formulation. The Cmax values demonstrated a 3.9-fold increase for the amorphous CBD powder formulation containing polyvinylpyrrolidone (PVP) as a polymer (F3) and a 3.0-fold increase for the amorphous CBD powder formulation containing hydroxypropyl methylcellulose (HPMC) as a polymer (F4) comp
     • Relative bioavailability · full text, p.4:ow) at- ferences were observed between F1 and F2, the amor- tributed to the melting endotherm of CBD. In contrast, phous CBD formulation F2 yielded a 5.4-fold signifi- the developed amorphous CBD powder formulations cantly higher AUC0–6h compared with the Control (F1–F4) showed a complete disappearance of the melt- (Table 2). ing endothermic peak derived from CBD, indicating the The time course of
     • Relative bioavailability · full text, p.5:lations containing 20% which were significantly different. Additionally, F3 and CBD, 50% PVP, and 30% emulsifier (F3) and 20% CBD, F4 showed 3.9- and 3.0-fold higher Cmax values than 50% HPMC, and 30% emulsifier (F4) showed higher those of the Control, respectively, but the differences plasma CBD concentrations from 0.5 to 4 h after admin- were not significant. Although there was no significant is
     • Food effect · full text, p.3:ebruary 6, 2023) and conducted in accordance with the company’s animal experimentation regulations. Rats were kept in a pathogen-free environment and fed ad libitum on food (MF solids) and water. They were maintained under a 12-h light/dark cycle (lights on: 7:00–19:00) in a temperature- and humidity-controlled room (19.5–26.4˚C; 34.5–75.4%). Twelve male Sprague–Dawley rats (8 wk old) were randoml
     • Form comparison · full text, p.1:as a polymer (F3) and a 3.0-fold increase for the amorphous CBD powder formulation containing hydroxypropyl methylcellulose (HPMC) as a polymer (F4) compared to the CBD isolate powder. Furthermore, the AUC0–6h values for F3 and F4 were 5.3- and 5.2-fold higher than those for CBD isolate powder, respectively, indicating a significant enhancement. The Tmax values were also significantly shorter for
     • Form comparison · full text, p.3:The CBD conjugate time curve (AUC), or the time to reach the maximum was hydrolyzed by incubating the mixture at 37˚C for plasma concentration (Tmax) compared to oral gavage 4 h, Then, 15 mL of methanol with phenprocoumon administration. Based on the previously established (500 ng/mL) as an internal standard and 0.5 mL of a average body weight of 260 g, approximately 10 mg 1 : 1 mixture of ethyl a
     • Form comparison · full text, p.4:n amorphous state. trations in rats: effect of adding an emulsifier. Plasma Bioavailability of amorphous CBD powder formulations in CBD concentration vs. time plots after oral administra- rats tion of CBD isolate powder and amorphous CBD pow- der formulations (F1 and F2) at a CBD dose of 10 mg/ Total plasma CBD concentrations at 0, 0.5, 1, 2, 4, kg (n54 per group). Statistical differences were and
106. Other animalEfficacy, pharmacokinetics and safety of liposomal synthetic cannabidiol injected subcutaneously in dogs: a randomized, blinded, placebo-controlled, crossover clinical trial.
     Front Vet Sci, 2025 · Design: randomized; crossover · n: 8 dogs · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 41635790DOI 10.3389/fvets.2025.1746266PMC12862949 (free full text)PDF
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     • Key findings · abstract:Blood was sampled for CBD and metabolites concentrations, complete blood count and serum chemistry up to 4-weeks post-injections.
     • Key findings · abstract:RESULTS: CBD plasma concentrations were detected up to 4-weeks; median peak plasma concentration (Cmax) was 58.2 [range 35.1-141.0] ng/mL, median time to Cmax was 3 [3-7] days and median half-life 6.1 [4.6-9.5] days.
     • Cmax · abstract:RESULTS: CBD plasma concentrations were detected up to 4-weeks; median peak plasma concentration (Cmax) was 58.2 [range 35.1-141.0] ng/mL, median time to Cmax was 3 [3-7] days and median half-life 6.1 [4.6-9.5] days.
     • Cmax · full text, Table 2:Pharmacokinetic data of plasma cannabidiol (CBD) from eight dogs after liposomal-synthetic-CBD (L-sCBD; 7 mg/kg) subcutaneous injection. Dog Cmax(ng/mL) Tmax(days) Half-life(days) AUC(ng·d/mL) AUC/dose(ng·d/mL/mg/kg) MRT (days) 1 56.1 3 5.4# 740 105.7 9.9 2 118.2 3 9.1 902 128.9 6.6 3 58.6 3 4.9 492 70.3 6.2 4 35.1 7 8.2 491 70.1 11.9 5 106.7 3 4.6 1,011 144.4 6.9 6 141.0 3 6.6 1,039 148.4 7.
     • Cmax · full text, Section 'Pharmacokinetics':Compared with six dogs administered a lower single-dose of 5 mg/kg L-sCBD, the median Cmax (45.2 [17.8–72.5] ng/mL) and AUC (490 [189–803] ng·d/mL) were higher in the present study, while the median Tmax (4 [2–14]) days was similar (16).
     • Cmax · full text, Section 'Pharmacokinetics':When comparing the results of the present study and the study where 5 mg/kg L-sCBD was injected, it seems that the effect of increasing L-sCBD dose on Cmax is positive, as was reported in horses after oral CBD administration (27).
     • Tmax · full text, Table 2:rmacokinetic data of plasma cannabidiol (CBD) from eight dogs after liposomal-synthetic-CBD (L-sCBD; 7 mg/kg) subcutaneous injection. Dog Cmax(ng/mL) Tmax(days) Half-life(days) AUC(ng·d/mL) AUC/dose(ng·d/mL/mg/kg) MRT (days) 1 56.1 3 5.4# 740 105.7 9.9 2 118.2 3 9.1 902 128.9 6.6 3 58.6 3 4.9 492 70.3 6.2 4 35.1 7 8.2 491 70.1 11.9 5 106.7 3 4.6 1,011 144.4 6.9 6 141.0 3 6.6 1,039 148.4 7.3 7 57.8
     • Tmax · full text, Section 'Pharmacokinetics':Compared with six dogs administered a lower single-dose of 5 mg/kg L-sCBD, the median Cmax (45.2 [17.8–72.5] ng/mL) and AUC (490 [189–803] ng·d/mL) were higher in the present study, while the median Tmax (4 [2–14]) days was similar (16).
     • AUC · full text, Table 2:cannabidiol (CBD) from eight dogs after liposomal-synthetic-CBD (L-sCBD; 7 mg/kg) subcutaneous injection. Dog Cmax(ng/mL) Tmax(days) Half-life(days) AUC(ng·d/mL) AUC/dose(ng·d/mL/mg/kg) MRT (days) 1 56.1 3 5.4# 740 105.7 9.9 2 118.2 3 9.1 902 128.9 6.6 3 58.6 3 4.9 492 70.3 6.2 4 35.1 7 8.2 491 70.1 11.9 5 106.7 3 4.6 1,011 144.4 6.9 6 141.0 3 6.6 1,039 148.4 7.3 7 57.8 3 5.6 645 92.1 7.9 8 56.6 7
     • AUC · full text, Section 'Pharmacokinetics':Compared with six dogs administered a lower single-dose of 5 mg/kg L-sCBD, the median Cmax (45.2 [17.8–72.5] ng/mL) and AUC (490 [189–803] ng·d/mL) were higher in the present study, while the median Tmax (4 [2–14]) days was similar (16).
     • AUC · full text, Section 'Pharmacokinetics':When the median AUC was normalized to dose (AUC per mg/kg dose administered), both studies showed the same AUC (98 versus 99 ng·d/mL/mg/kg), suggesting proportional increase in exposure with dose increase.
     • Form comparison · full text, Table 7:ts and follow-up of eight dogs with naturally-occurring osteoarthritis after liposomal-synthetic-cannabidiol (L-sCBD; 7 mg/kg) subcutaneous injection compared with placebo injection. Dog Fever1 Local response2 Follow-up 1 No Yes Per owner request, continued receiving L-sCBD injections every 4–10 weeks (total injections 16).Was diagnosed with anal sac carcinoma and lung metastasis 2 years & 3 month
     • Form comparison · full text, Section 'Behavior, activity monitoring collar, la':Specifically, 100% of dogs post-L-sCBD injection demonstrated improved function compared to only 25% post-placebo injection.
     • Form comparison · full text, Section 'Pharmacokinetics':Compared with six dogs administered a lower single-dose of 5 mg/kg L-sCBD, the median Cmax (45.2 [17.8–72.5] ng/mL) and AUC (490 [189–803] ng·d/mL) were higher in the present study, while the median Tmax (4 [2–14]) days was similar (16).
107. Other animalLimited 12-hour pharmacokinetic assessment of CBD and CBDA isolates compared to their full-spectrum extracts in healthy adult beagles.
     Front Vet Sci, 2025 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 40874201DOI 10.3389/fvets.2025.1639846PMC12379728 (free full text)PDF
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     • Key findings · abstract:CBDA showed higher Cmax and AUC than CBD in both isolate and FS forms (p < 0.001).
     • Cmax · abstract:CBDA showed higher Cmax and AUC than CBD in both isolate and FS forms (p < 0.001).
     • Tmax · abstract:CBDA in CBD/CBDA FS had a shorter Tmax compared to CBD (p = 0.019).
     • AUC · abstract:CBDA showed higher Cmax and AUC than CBD in both isolate and FS forms (p < 0.001).
     • Cmax · full text, Section 'Twelve-hour pharmacokinetics':For Cmax, CBDA isolate had a higher peak serum concentration compared to CBD isolate (235.51 ± 65.59 vs. 69.80 ± 35.44 ng/mL, p < 0.001).
     • Cmax · full text, Section 'Twelve-hour pharmacokinetics':CBDA in CBD/CBDA FS had a higher Cmax than CBD in the same formulation (229.30 ± 145.51 vs. 64.66 ± 37.05 ng/mL, p < 0.001).
     • Tmax · full text, Section 'Twelve-hour pharmacokinetics':For Tmax, CBDA in CBD/CBDA FS reached peak concentration earlier than CBD in the same formulation (1.81 ± 2.55 vs. 3.75 ± 2.71 h, p = 0.019).
     • AUC · full text, Section 'Twelve-hour pharmacokinetics':For AUC, CBDA isolate had a higher AUC than CBD isolate (1255.70 ± 463.52 vs. 420.61 ± 45.52 ng·h/mL, p < 0.001).
     • AUC · full text, Section 'Twelve-hour pharmacokinetics':CBDA in CBD/CBDA FS had a higher AUC than CBD in the same formulation (1240.97 ± 450.55 vs. 354.45 ± 124.65 ng·h/mL, p < 0.001).
     • Form comparison · full text, Section 'Twelve-hour pharmacokinetics':For Cmax, CBDA isolate had a higher peak serum concentration compared to CBD isolate (235.51 ± 65.59 vs. 69.80 ± 35.44 ng/mL, p < 0.001).
     • Form comparison · full text, Section 'Twelve-hour pharmacokinetics':CBDA in CBD/CBDA FS had a higher Cmax than CBD in the same formulation (229.30 ± 145.51 vs. 64.66 ± 37.05 ng/mL, p < 0.001).
     • Form comparison · full text, Section 'Twelve-hour pharmacokinetics':For Tmax, CBDA in CBD/CBDA FS reached peak concentration earlier than CBD in the same formulation (1.81 ± 2.55 vs. 3.75 ± 2.71 h, p = 0.019).
108. Other animalFormulation and Evaluation of Solid Self-Nanoemulsifying Drug Delivery System of Cannabidiol for Enhanced Solubility and Bioavailability.
     Pharmaceutics, 2025 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 40143004DOI 10.3390/pharmaceutics17030340PMC11944824 (free full text)
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Cmax · full text, Table 9:ed following the oral administration of CBD-loaded SNEDDS and oil-based formulations in rats (n = 3–4). All values are presented as mean ± SEM. Group Cmax(ng/mL) AUC0–4 h(ng/mL·h) AUC0–24 h(ng/mL·h) AUC0–∞(ng/mL·h) Tmax(h) T1/2(h) L-SNEDDS 499.5 ± 144.6 * 1255.4 ± 368.4 *# 1504.6 ± 427.7 * 1534.3 ± 438.9 1.3 ± 0.3 **## 4.8 ± 1.8 S-SNEDDS-SD 283.7 ± 84.7 * 616.2 ± 162.2 *# 808.0 ± 219.4 * 833.8 ± 2
     • Cmax · full text, Section '3.6. In Vivo Pharmacokinetic Study':The Cmax for L-SNEDDS, S-SNEDDS-SCA, S-SNEDDS-SD, CBD-MCT, and CBD-sesame oil was determined to be 499.5 ± 144.6 (L-SNEDDS, highest), 146.7 ± 26.0, 283.7 ± 84.7, 13.4 ± 4.2 (CBD-MCT, lowest), and 186.2 ± 31.4 ng/mL, respectively.
     • Cmax · full text, Section '3.6. In Vivo Pharmacokinetic Study':While the oil-based formulations exhibited a delayed absorption of CBD, lasting until 6~7 h, the SNEDDS formulations led to a rapid absorption rate and a relatively high Cmax.
     • Tmax · full text, Table 9:-based formulations in rats (n = 3–4). All values are presented as mean ± SEM. Group Cmax(ng/mL) AUC0–4 h(ng/mL·h) AUC0–24 h(ng/mL·h) AUC0–∞(ng/mL·h) Tmax(h) T1/2(h) L-SNEDDS 499.5 ± 144.6 * 1255.4 ± 368.4 *# 1504.6 ± 427.7 * 1534.3 ± 438.9 1.3 ± 0.3 **## 4.8 ± 1.8 S-SNEDDS-SD 283.7 ± 84.7 * 616.2 ± 162.2 *# 808.0 ± 219.4 * 833.8 ± 214.7 1.0 ± 0.0 **### 4.5 ± 1.2 S-SNEDDS-SCA 146.7 ± 26.0 ** 396.2
     • Tmax · full text, Section '3.6. In Vivo Pharmacokinetic Study':The Tmax value for CBD-MCT administration (6.7 ± 0.7 h) was similar to that of CBD-sesame oil (6.5 ± 0.5 h), while Tmax for L-SNEDDS, S-SNEDDS-SCA, and S-SNEDDS-SD administration (1.3 ± 0.3, 2.0 ± 0.0, 1.0 ± 0.0 h) was shorter compared with the oil-based formulations.
     • Tmax · full text, Section '3.6. In Vivo Pharmacokinetic Study':Figure 13 suggests that CBD was absorbed rapidly (Tmax within 2 h) following the administration in the SNEDDS, which is rationally attributed to the augmentation of the surface absorption area offered by the nanoemulsification process in the gastrointestinal tract.
     • AUC · full text, Table 9:the oral administration of CBD-loaded SNEDDS and oil-based formulations in rats (n = 3–4). All values are presented as mean ± SEM. Group Cmax(ng/mL) AUC0–4 h(ng/mL·h) AUC0–24 h(ng/mL·h) AUC0–∞(ng/mL·h) Tmax(h) T1/2(h) L-SNEDDS 499.5 ± 144.6 * 1255.4 ± 368.4 *# 1504.6 ± 427.7 * 1534.3 ± 438.9 1.3 ± 0.3 **## 4.8 ± 1.8 S-SNEDDS-SD 283.7 ± 84.7 * 616.2 ± 162.2 *# 808.0 ± 219.4 * 833.8 ± 214.7 1.0 ± 0.
     • AUC · full text, Section '3.6. In Vivo Pharmacokinetic Study':As presented in Table 9, the AUC0–4 h value of CBD from SNEDDS formulations was significantly greater than that of oil-based formulations during the first 4 h.
     • AUC · full text, Section '3.6. In Vivo Pharmacokinetic Study':Additionally, the AUC value of CBD for SNEDDS formulations was also contrasted with oil-based formulations from 0 to 24 h.
     • Relative bioavailability · full text, Section '3.6. In Vivo Pharmacokinetic Study':However, the ratio of the AUC0–24 h value of CBD relative to CBD-sesame oil was 1.2-, 0.6-, and 0.5-fold for L-SNEDDS, S-SNEDDS-SD, and S-SNEDDS-SCA formulations, respectively.
     • Food effect · full text, Section '2.8.2. In Vivo Pharmacokinetic Study':The rats underwent fasting for 12 h before the administration, and food was given after 6 h of drug administration.
     • Food effect · full text, Section '3.6. In Vivo Pharmacokinetic Study':The feeding time of the animals was different in the two studies; the rats were fed 6 h after the oral administration (this study) and 2 h after (previous research).
     • Form comparison · full text, Section '3.1.4. Characterization of CBD-Loaded SN':As shown in Figure 3B, compared with the SNEDDS formulation with 10% MCT, when the proportion of MCT increased to 20%, the dissolution of SNEDDS in the pH 1.0 medium was decreased by approximately 10% (from 94.59 ± 0.66% to 83.48 ± 4.59% in 1 h).
     • Form comparison · full text, Section '3.6. In Vivo Pharmacokinetic Study':The Tmax value for CBD-MCT administration (6.7 ± 0.7 h) was similar to that of CBD-sesame oil (6.5 ± 0.5 h), while Tmax for L-SNEDDS, S-SNEDDS-SCA, and S-SNEDDS-SD administration (1.3 ± 0.3, 2.0 ± 0.0, 1.0 ± 0.0 h) was shorter compared with the oil-based formulations.
     • Form comparison · full text, Section '4. Conclusions':Meanwhile, compared with the two oil-based formulations (CBD-sesame oil (similar to Epidiolex®) and CBD-MCT), oral administration of L-SNEDDS and spray drying S-SNEDDS formulations resulted in faster absorption of CBD (Tmax: 6~8 h (CBD oils), 1~2 h (SNEDDS formulations); p < 0.05 compared with two controls) and higher blood concentrations (p < 0.05 compared with CBD-MCT), which were essential for
109. Other animalPreclinical assessment of pharmacokinetics and anticonvulsant activity of CBDTech, a novel orally administered cannabidiol (CBD) formulation for seizure and epilepsy.
     J Cannabis Res, 2025 · Design: not stated · n: n = 10 · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 41029806DOI 10.1186/s42238-025-00322-7PMC12487286 (free full text)
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     • Key findings · abstract:For the PK studies, Sprague Dawley rats were orally administered 25 mg/kg CBD in MCT oil or test formulations incorporating DehydraTECH™ (n = 10 per group).
     • Key findings · abstract:Area under the curve from dosing to the last measurable concentration (AUClast) was 391 to 2708% improved following treatment with DehydraTECH™ formulations as compared with the MCT control (all p < 0.01).
     • AUC · abstract:Area under the curve from dosing to the last measurable concentration (AUClast) was 391 to 2708% improved following treatment with DehydraTECH™ formulations as compared with the MCT control (all p < 0.01).
     • Cmax · full text, Table 2:armacokinetics after oral administration of various formulations of 25 mg/kg CBD in male Sprague–Dawley rats (n = 10 per group) Test Article tmax(hr) Cmax(ng/mL) AUClast(hr•ng/mL) AUClast/dose(hr•kg•ng/mL/mg) MCT Control 0.95 ± 0.11 25.8 ± 12.0 13.2 ± 6.8a 0.53 ± 0.27a Original DehydraTECH™ 1.0 0.83 ± 0.21 112.2 ± 46.6 64.6 ± 23.7a 2.58 ± 0.95a Original DehydraTECH™ 2.0 0.75 ± 0.12 234.6 ± 111.0*
     • Cmax · full text, Section 'Determination of CBDtech plasma PK, brai':Cmax was significantly improved following administration of Original DehydraTECH™ 2.0 (807.6%; p < 0.001), New DehydraTECH™ 2.0, formulation 5 (515.2%; p = 0.007), and New DehydraTECH™ 2.0, formulation 6 (1064.5%; p < 0.001) as compared with the MCT control.
     • Tmax · full text, Table 2:plasma pharmacokinetics after oral administration of various formulations of 25 mg/kg CBD in male Sprague–Dawley rats (n = 10 per group) Test Article tmax(hr) Cmax(ng/mL) AUClast(hr•ng/mL) AUClast/dose(hr•kg•ng/mL/mg) MCT Control 0.95 ± 0.11 25.8 ± 12.0 13.2 ± 6.8a 0.53 ± 0.27a Original DehydraTECH™ 1.0 0.83 ± 0.21 112.2 ± 46.6 64.6 ± 23.7a 2.58 ± 0.95a Original DehydraTECH™ 2.0 0.75 ± 0.12 234.6
     • Tmax · full text, Section 'Determination of CBDtech plasma PK, brai':With the exception of New DehydraTECH™ 2.0, formulation 5 (Tmax = 1.68 h; p < 0.001), remaining formulations had a Tmax that was less than one hour post dose and did not significantly differ from MCT control.
     • AUC · full text, Table 2:cs after oral administration of various formulations of 25 mg/kg CBD in male Sprague–Dawley rats (n = 10 per group) Test Article tmax(hr) Cmax(ng/mL) AUClast(hr•ng/mL) AUClast/dose(hr•kg•ng/mL/mg) MCT Control 0.95 ± 0.11 25.8 ± 12.0 13.2 ± 6.8a 0.53 ± 0.27a Original DehydraTECH™ 1.0 0.83 ± 0.21 112.2 ± 46.6 64.6 ± 23.7a 2.58 ± 0.95a Original DehydraTECH™ 2.0 0.75 ± 0.12 234.6 ± 111.0* 134.7 ± 63.7
     • AUC · full text, Section 'Determination of CBDtech plasma PK, brai':Similarly, AUClast was significantly improved following administration of Original DehydraTECH™ 2.0 (923.4%; p = 0.019), New DehydraTECH™ 2.0, formulation 5 (1322.8%; p < 0.001), and New DehydraTECH™ 2.0, formulation 6 (2707.3%; p < 0.001) as compared with the MCT control.
     • AUC · full text, Section 'Determination of CBDtech plasma PK, brai':Moreover, AUClast was significantly improved following administration of New DehydraTECH™ 2.0, formulation 5 (190.0%; p = 0.032), and New DehydraTECH™ 2.0, formulation 6 (472.4%; p < 0.001) as compared with Original DehydraTECH™ 1.0.
     • Relative bioavailability · full text, Section 'MES Induction':This stimulus was ~ 5–10 times higher than the individual animal electrical seizure threshold, eliminating bias stemming from daily fluctuations in seizure threshold.
     • Form comparison · full text, Section 'Determination of CBDtech plasma PK, brai':Cmax was significantly improved following administration of Original DehydraTECH™ 2.0 (807.6%; p < 0.001), New DehydraTECH™ 2.0, formulation 5 (515.2%; p = 0.007), and New DehydraTECH™ 2.0, formulation 6 (1064.5%; p < 0.001) as compared with the MCT control.
     • Form comparison · full text, Section 'Determination of CBDtech plasma PK, brai':Similarly, AUClast was significantly improved following administration of Original DehydraTECH™ 2.0 (923.4%; p = 0.019), New DehydraTECH™ 2.0, formulation 5 (1322.8%; p < 0.001), and New DehydraTECH™ 2.0, formulation 6 (2707.3%; p < 0.001) as compared with the MCT control.
     • Form comparison · full text, Section 'Determination of CBDtech plasma PK, brai':Moreover, AUClast was significantly improved following administration of New DehydraTECH™ 2.0, formulation 5 (190.0%; p = 0.032), and New DehydraTECH™ 2.0, formulation 6 (472.4%; p < 0.001) as compared with Original DehydraTECH™ 1.0.
110. Other animalPharmacokinetics of cannabidiol, (-)-trans-Δ9-tetrahydrocannabinol, and their oxidative metabolites after intravenous and oral administration of a cannabidiol-dominant full-spectrum hemp product to beagle dogs.
     Front Vet Sci, 2025 · Design: not stated · n: n = 4 · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 40264990DOI 10.3389/fvets.2025.1556975PMC12013723 (free full text)
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     • Key findings · abstract:Blood samples were collected at predetermined times to measure concentrations of serum CBD, 7-hydroxy-CBD (7-OH-CBD), 7-nor-7-carboxy-CBD (7-COOH-CBD), Δ9-tetrahydrocannabinol (Δ9-THC), 11-hydroxy-THC (11-OH-THC), and 11-carboxy-THC (11-COOH-THC).
     • Key findings · abstract:Serum CBD and Δ9-THC concentrations were analyzed to estimate various pharmacokinetic parameters.
     • Key findings · abstract:The AUC0-∞ for 7-OH-CBD after single IV compared to single PO dose was not different, suggesting complete absorption of CBD from the formulation in MCT oil when administered with canned dog food.
     • AUC · abstract:The AUC0-∞ for 7-OH-CBD after single IV compared to single PO dose was not different, suggesting complete absorption of CBD from the formulation in MCT oil when administered with canned dog food.
     • Cmax · full text, Table 1:mum Single dose IV administration of CBD in test article diluted in ethanol λz 1/min 0.00241 0.00136 0.00379 t1/2 min 291 183 508 Tmax min 5 5 5 Cmax ng/mL 2.20 × 103 1.87 × 103 3.29 × 103 C0 ng/mL 2.45 × 103 2.17 × 103 3.57 × 103 AUC_0−∞_obs ng h/mL 5,196 3,486 5,972 MRT 0−∞_obs min 277 179 429 Vz_obs L/kg 3.11 1.62 6.26 Cl_obs mL/min/kg 7.06 6.14 10.5 Vss, obs L/kg 2.13 1.10 2.85 ER % 57 44
     • Cmax · full text, Table 2:57 Single PO dose of Δ9-THC in test article mixed with moist dog food λz 1/min 0.00153 0.000511 0.00423 t1/2 min 455 164 1,357 Tmax min 120 60 480 Cmax ng/mL 4.76 2.55 9.89 Tlag min 17.5 0 60 AUC 0−∞_obs ng h/mL 35.8 26.8 48.3 MRT 0−∞_obs min 610 263 1,473 Vz/F_obs L/kg 14.0 6.48 39.1 Cl/F_obs mL/min/kg 0.0253 0.0186 0.0335 F % 40.9 20.5 46.2
     • Cmax · full text, Table 3:Median (range) Cmax and AUC0 − t for CBD, 7-OH-CBD, and 7-COOH-CBD after single dose IV and PO CBD at 2.2 mg/kg body weight. Parameter CBD 7-OH-CBD 7-COOH-CBD CBD and metabolites after IV administration of CBD Cmax, ng/mL 2,196 (1,870–3,290) 7.04 (3.42–14.40)
     • Tmax · full text, Table 1:Minimum Maximum Single dose IV administration of CBD in test article diluted in ethanol λz 1/min 0.00241 0.00136 0.00379 t1/2 min 291 183 508 Tmax min 5 5 5 Cmax ng/mL 2.20 × 103 1.87 × 103 3.29 × 103 C0 ng/mL 2.45 × 103 2.17 × 103 3.57 × 103 AUC_0−∞_obs ng h/mL 5,196 3,486 5,972 MRT 0−∞_obs min 277 179 429 Vz_obs L/kg 3.11 1.62 6.26 Cl_obs mL/min/kg 7.06 6.14 10.5 Vss, obs L/kg 2.13 1.10 2
     • Tmax · full text, Table 2:3 91 (1-ER) % 44 9.0 57 Single PO dose of Δ9-THC in test article mixed with moist dog food λz 1/min 0.00153 0.000511 0.00423 t1/2 min 455 164 1,357 Tmax min 120 60 480 Cmax ng/mL 4.76 2.55 9.89 Tlag min 17.5 0 60 AUC 0−∞_obs ng h/mL 35.8 26.8 48.3 MRT 0−∞_obs min 610 263 1,473 Vz/F_obs L/kg 14.0 6.48 39.1 Cl/F_obs mL/min/kg 0.0253 0.0186 0.0335 F % 40.9 20.5 46.2
     • AUC · full text, Table 1:min 0.00241 0.00136 0.00379 t1/2 min 291 183 508 Tmax min 5 5 5 Cmax ng/mL 2.20 × 103 1.87 × 103 3.29 × 103 C0 ng/mL 2.45 × 103 2.17 × 103 3.57 × 103 AUC_0−∞_obs ng h/mL 5,196 3,486 5,972 MRT 0−∞_obs min 277 179 429 Vz_obs L/kg 3.11 1.62 6.26 Cl_obs mL/min/kg 7.06 6.14 10.5 Vss, obs L/kg 2.13 1.10 2.85 ER % 57 44 80 1-ER % 43 20 56 Single dose PO administration of CBD in test article mixed with
     • AUC · full text, Table 2:ta min 169 139 476 C0 ng/mL 51.4 44.6 70.3 V mL/kg 1,052 768 1,209 CL mL/min/kg 8.85 6.88 14.38 V2 mL/kg 867 488 1,197 CL2 mL/min/kg 15.7 0.8132 40.0 AUC0−∞ ng h/mL 102 62.5 131 AUMC ng min2/mL 1.29 × 106 0.602 × 106 1.49 × 106 MRT min 203 160 230 Vss L/kg 1.98 1.30 2.30 ER % 56 43 91 (1-ER) % 44 9.0 57 Single PO dose of Δ9-THC in test article mixed with moist dog food λz 1/min 0.00153 0.000511
     • AUC · full text, Table 3:Median (range) Cmax and AUC0 − t for CBD, 7-OH-CBD, and 7-COOH-CBD after single dose IV and PO CBD at 2.2 mg/kg body weight. Parameter CBD 7-OH-CBD 7-COOH-CBD CBD and metabolites after IV administration of CBD Cmax, ng/mL 2,196 (1,870–3,290) 7.04 (3.42–14.40) 47.7 (3
     • Food effect · full text, Section '2.2 Dogs and outcome assessment':All dogs were fed Purina Pro Plan Adult Complete Essentials Shredded Blend Chicken & Rice dry dog food (minimum 18.2% crude fat, 29.5% crude protein dry matter basis) twice daily during the acclimation period and throughout the study.
     • Food effect · full text, Section '2.2 Dogs and outcome assessment':Approximately 10–20 g of canned dog food1 (minimum 31.8% crude fat, 36.4% crude protein dry matter basis) was fed during Phases 2 and 3 to deliver the test article.
     • Form comparison · full text, Table 1:03 2.17 × 103 3.57 × 103 AUC_0−∞_obs ng h/mL 5,196 3,486 5,972 MRT 0−∞_obs min 277 179 429 Vz_obs L/kg 3.11 1.62 6.26 Cl_obs mL/min/kg 7.06 6.14 10.5 Vss, obs L/kg 2.13 1.10 2.85 ER % 57 44 80 1-ER % 43 20 56 Single dose PO administration of CBD in test article mixed with moist dog food λz 1/min 0.00187 0.000888 0.00286 t1/2 min 420 243 781 Tmax min 120 60 480 Cmax ng/mL 270 118 537 Tlag min 0
     • Form comparison · full text, Table 2:mL/kg 867 488 1,197 CL2 mL/min/kg 15.7 0.8132 40.0 AUC0−∞ ng h/mL 102 62.5 131 AUMC ng min2/mL 1.29 × 106 0.602 × 106 1.49 × 106 MRT min 203 160 230 Vss L/kg 1.98 1.30 2.30 ER % 56 43 91 (1-ER) % 44 9.0 57 Single PO dose of Δ9-THC in test article mixed with moist dog food λz 1/min 0.00153 0.000511 0.00423 t1/2 min 455 164 1,357 Tmax min 120 60 480 Cmax ng/mL 4.76 2.55 9.89 Tlag min 17.5 0 60 AUC
     • Form comparison · full text, Section '3.3.1 Serum CBD, Δ9-THC, and metabolites':Plots of log serum concentrations of CBD, 7-OH-CBD, and 7-COOH-CBD vs. time after single IV administration of CBD at a dose of 2.2 mg/kg BW are reported in Figure 3.
111. Other animalEnhancement of cannabidiol oral bioavailability through the development of nanostructured lipid carriers: In vitro and in vivo evaluation studies.
     Drug Deliv Transl Res, 2025 · Design: not stated · full text (Europe PMC XML) + abstract · open access (hybrid)
     PMID 39738884DOI 10.1007/s13346-024-01766-9PMC12214004 (free full text)
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:The in vivo pharmacokinetic study of NLC5 formulation showed 27% CBD oral bioavailability.
     • Cmax · full text, Section 'In vivo pharmacokinetics':As shown in Fig. 4a, the formulated CBD NLCs exhibited a Cmax of 101.5 ng/mL, a Tmax, of 4 h, in contrast, the Cmax for CBD IV was 1028 ng/mL as shown in Fig. 4b.Fig. 4CBD plasma conc (ng/mL) after administration of (a) oral CBD NLC5 and (b) CBD IV solution in rats
     • Tmax · full text, Section 'In vivo pharmacokinetics':As shown in Fig. 4a, the formulated CBD NLCs exhibited a Cmax of 101.5 ng/mL, a Tmax, of 4 h, in contrast, the Cmax for CBD IV was 1028 ng/mL as shown in Fig. 4b.Fig. 4CBD plasma conc (ng/mL) after administration of (a) oral CBD NLC5 and (b) CBD IV solution in rats
     • AUC · full text, Section 'In vivo pharmacokinetics':The results of the analysis revealed that CBD NLC and CBD IV showed AUC of 1376.7 ng.h/mL and 1010.64 ng.h/mL respectively.
     • Form comparison · full text, Section 'Screening and selection of lipids and su':The results of the oil screening test showed that CBD exhibited higher solubility in sesame oil (40 mg CBD / mL) compared to castor oil (29 mg CBD / mL).
     • Form comparison · full text, Section 'In vivo pharmacokinetics':Figure 4 is a graphical representation of the CBD plasma concentration-time curves following oral gavage administration of CBD NLC5 contains 5 mg CBD versus IV administration of 1 mg CBD.
112. Other animalLiposomal-synthetic-cannabidiol: preliminary translational evidence of efficacy, tolerability and pharmacokinetics following repeated subcutaneous injections in two goats.
     Front Pharmacol, 2025 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 41293235DOI 10.3389/fphar.2025.1689226PMC12641115 (free full text)PDF
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     • Key findings · abstract:Blood samples were collected for assessment of plasma concentrations, complete blood count (CBC), and biochemical analysis before and up to 6 weeks after each injection.
     • Key findings · abstract:The CBD peak plasma concentration (Cmax) was 4.4-28.2 ng/mL, while its primary metabolite, 7-carboxy-CBD (7-COOH-CBD), was much higher (129-1,524 ng/mL), similar to those in reports of humans.
     • Key findings · abstract:The time to Cmax and half-life of CBD were 0.25-21 and 5.1-24.2 days, respectively, and those in 7-COOH-CBD were 3-28 and 5.6-24.5 days, respectively.
     • Cmax · abstract:The CBD peak plasma concentration (Cmax) was 4.4-28.2 ng/mL, while its primary metabolite, 7-carboxy-CBD (7-COOH-CBD), was much higher (129-1,524 ng/mL), similar to those in reports of humans.
     • Cmax · abstract:The time to Cmax and half-life of CBD were 0.25-21 and 5.1-24.2 days, respectively, and those in 7-COOH-CBD were 3-28 and 5.6-24.5 days, respectively.
     • Cmax · full text, Section 'Pharmacokinetics':Compared with six dogs administered a single dose of 5 mg/kg liposomal CBD, median Cmax (45.2 [17.8–72.5] ng/mL) and AUC (490 [189–803] ng·day/mL) in the dogs were higher than those in the goats, while Tmax (4 [2–14]) days] in the dogs was similar to that in the goats (Shilo-Benjamini et al., 2023).
     • Cmax · full text, Section 'Pharmacokinetics':In addition, in adult healthy volunteers, Cmax ranged from 292 to 782 ng/mL, depending on the administered dose (1,500–6,000 mg).
     • Cmax · full text, Section 'Pharmacokinetics':Twenty-four hours after administration of Epidiolex® in healthy volunteers, CBD levels decreased rapidly to approximately 10% of the Cmax value, with a half-life of approximately 15 h and no dose effect (Taylor et al., 2018).
     • Tmax · full text, Section 'Pharmacokinetics':Compared with six dogs administered a single dose of 5 mg/kg liposomal CBD, median Cmax (45.2 [17.8–72.5] ng/mL) and AUC (490 [189–803] ng·day/mL) in the dogs were higher than those in the goats, while Tmax (4 [2–14]) days] in the dogs was similar to that in the goats (Shilo-Benjamini et al., 2023).
     • Tmax · full text, Section 'Pharmacokinetics':Following administration of Epidiolex® in adults and children, the pharmacokinetics obtained were typical to that of oral administration with Tmax, most commonly observed in 3–5 h after ingestion (Britch et al., 2021).
     • AUC · full text, Section 'Pharmacokinetics':Compared with six dogs administered a single dose of 5 mg/kg liposomal CBD, median Cmax (45.2 [17.8–72.5] ng/mL) and AUC (490 [189–803] ng·day/mL) in the dogs were higher than those in the goats, while Tmax (4 [2–14]) days] in the dogs was similar to that in the goats (Shilo-Benjamini et al., 2023).
     • Form comparison · full text, Section 'Pharmacokinetics':Compared with six dogs administered a single dose of 5 mg/kg liposomal CBD, median Cmax (45.2 [17.8–72.5] ng/mL) and AUC (490 [189–803] ng·day/mL) in the dogs were higher than those in the goats, while Tmax (4 [2–14]) days] in the dogs was similar to that in the goats (Shilo-Benjamini et al., 2023).
     • Form comparison · full text, Section 'Analgesia':A recent study in humans with temporomandibular disorders reported that low CBD doses of 40 or 20 mg mixed in hydrogel and administered locally (bilateral intraoral on the masseter muscles) provided significant pain reduction, reduction in muscle tension, and alleviation of sleep bruxism compared with the vehicle control (Walczynska-Dragon et al., 2024).
     • Form comparison · full text, Section 'Analgesia':Both metabolites at 40 mg/kg produced a significant decrease in ear thickness compared with the vehicle, which was comparable to indomethacin, with 7-OH-CBD producing a greater effect over 7-COOH-CBD (Mechoulam et al., 2010).
113. Other animalChronic oral dosing of cannabidiol and cannabidiolic acid full-spectrum hemp oil extracts has no adverse effects in horses: a pharmacokinetic and safety study.
     Am J Vet Res, 2025 · Design: randomized; crossover · abstract only (PubMed) · open access (gold)
     PMID 39787699DOI 10.2460/ajvr.24.08.0235
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:RESULTS: 12-hour pharmacokinetics revealed a higher maximum serum concentration (103 vs 12 ng/mL) and greater area under the curve (259 vs 62 ng·h/mL) for CBDA when compared to CBD.
     • Key findings · abstract:Cannabidiolic acid nadir and peak serum levels over time ranged from 46 to 122 ng/mL, which was higher than CBD (12 to 38 ng/mL).
     • Key findings · abstract:CONCLUSIONS: A dose of either 1 mg/kg of CBD or CBDA administered long term appears safe; however, CBDA serum concentrations suggest superior absorption/retention.
     • AUC · abstract:RESULTS: 12-hour pharmacokinetics revealed a higher maximum serum concentration (103 vs 12 ng/mL) and greater area under the curve (259 vs 62 ng·h/mL) for CBDA when compared to CBD.
114. Other animalOral formulations for cannabidiol: Improved absolute oral bioavailability of biodegradable cannabidiol self-emulsifying drug delivery systems.
     Colloids Surf B Biointerfaces, 2025 · Design: not stated · abstract only (PubMed) · open access (hybrid)
     PMID 40541033DOI 10.1016/j.colsurfb.2025.114879
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:The plasma CBD concentration following oral administration of the developed SEDDS suggested higher absolute bioavailability of the PG-based formulation (3.8 %) compared with Epidiolex (3.4 %).
     • Key findings · abstract:Additionally, the maximum plasma concentrations for the three developed SEDDS ranged from 30.6 to 35.8 ng/mL, surpassing that of Epidiolex (25.0 ng/mL).
115. Other animal[Pharmacokinetics and anti-inflammatory activity of cannabidiol/ γ-polyglutamic acid-g-cholesterol nanomicelles].
     Zhongguo Zhong Yao Za Zhi, 2025 · Design: not stated · abstract only (PubMed) · unknown
     PMID 39929634DOI 10.19540/j.cnki.cjcmm.20241106.201
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:Within 24 h, the tissue distribution concentration of CBD/(γ-PGA-g-CHOL)NMs was higher than that of CBD.
116. Other animalPheophytins as bioenhancers: Improving cannabidiol bioavailability and efficacy in cannabis extracts.
     Int J Pharm, 2025 · Design: not stated · abstract only (PubMed) · closed/paywalled
     PMID 40976326DOI 10.1016/j.ijpharm.2025.126194
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:A CBD-rich extract with a high content of CDs (high-chlorophyll extract) exhibited a 1.59-fold increase in aqueous dispersibility of CBD compared to an extract with a similar cannabinoid profile but lower CD content (low-chlorophyll extract) (p < 0.01).
     • Key findings · abstract:These enhancements translated into improved pharmacokinetic profiles, with more than a two-fold increase in both the maximum plasma concentration and the area under the concentration-time curve (p < 0.05, where applicable) for CBD in rats following oral administration of pheophytin-rich or enriched extracts.
     • AUC · abstract:These enhancements translated into improved pharmacokinetic profiles, with more than a two-fold increase in both the maximum plasma concentration and the area under the concentration-time curve (p < 0.05, where applicable) for CBD in rats following oral administration of pheophytin-rich or enriched extracts.
     • Relative bioavailability · abstract:A CBD-rich extract with a high content of CDs (high-chlorophyll extract) exhibited a 1.59-fold increase in aqueous dispersibility of CBD compared to an extract with a similar cannabinoid profile but lower CD content (low-chlorophyll extract) (p < 0.01).
     • Relative bioavailability · abstract:These enhancements translated into improved pharmacokinetic profiles, with more than a two-fold increase in both the maximum plasma concentration and the area under the concentration-time curve (p < 0.05, where applicable) for CBD in rats following oral administration of pheophytin-rich or enriched extracts.
117. Other animalA novel cannabidiol:tetramethylpyrazine cocrystal (CBD:TMP, ART12.11) improves the efficacy and bioavailability of cannabidiol in reducing stress-induced depressive and anxiety symptoms.
     Prog Neuropsychopharmacol Biol Psychiatry, 2025 · Design: not stated · abstract only (PubMed) · open access (hybrid)
     PMID 40854502DOI 10.1016/j.pnpbp.2025.111478
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:In addition, we investigated blood plasma concentrations of CBD and TMP following oral administration of ART12.11 to examine bioavailability.
     • Key findings · abstract:Further, we report that ART12.11 resulted in higher blood plasma levels of CBD and its major metabolite, indicating superior bioavailability.
118. Other animalLimited pharmacokinetic and safety study with daily feeding of hemp pellets in domestic goats: cannabidiolic acid is absorbed and retained better than cannabidiol.
     Am J Vet Res, 2025 · Design: not stated · abstract only (PubMed) · open access (gold)
     PMID 40840522DOI 10.2460/ajvr.25.03.0089
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:Serum samples were collected at 0, 0.5, 1, 2, 4, 8, 12, and 24 hours and at 7 and 14 days, from September through November of 2023.
     • Key findings · abstract:Serum concentrations for 12 cannabinoid/metabolites were determined using LC-MS.
     • Key findings · abstract:The maximum geometric mean serum concentration was 30.0 ng/mL (range, 21.3 to 59.2 mg/mL), the median time of maximum serum concentration was 18 hours (range, 4 to 24 hours), and the geometric mean area under the plasma concentration-versus-time curve was 410.2 ng·h/mL (range, 174.4 to 919.3 ng·h/mL).
     • Key findings · abstract:Mean ± SD serum concentrations 6 hours after administration on days 7 and 14 w[excerpt truncated in our database — see source]
     • AUC · abstract:The maximum geometric mean serum concentration was 30.0 ng/mL (range, 21.3 to 59.2 mg/mL), the median time of maximum serum concentration was 18 hours (range, 4 to 24 hours), and the geometric mean area under the plasma concentration-versus-time curve was 410.2 ng·h/mL (range, 174.4 to 919.3 ng·h/mL).
119. Other animalA Preliminary Evaluation of the Comparative Efficacy of Gel-Based and Oil-Based CBD on Hematologic and Biochemical Responses in Dogs.
     Vet Sci, 2025 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 40284843DOI 10.3390/vetsci12040342PMC12031437 (free full text)
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Food effect · full text, Section '2.1. Animals and Housing':During the 14-day acclimation period preceding the trial, all dogs were fed a standard commercial dry dog food containing at least 26.0% crude protein, 16.0% crude fat, and no more than 3.0% crude fiber.
120. Other animalRetinal pharmacodynamic and pharmacokinetic profile of cannabidiol in an in vivo model of retinal excitotoxicity.
     Eur J Pharmacol, 2025 · Design: not stated · abstract only (PubMed) · open access (hybrid)
     PMID 39892452DOI 10.1016/j.ejphar.2025.177323
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:CBD-NLC3 formulation, after a single topical administration, efficiently delivered CBD in the retina (Cmax = 98 ± 25.9 ng/mg;[excerpt truncated in our database — see source]
     • Cmax · abstract:CBD-NLC3 formulation, after a single topical administration, efficiently delivered CBD in the retina (Cmax = 98 ± 25.9 ng/mg;
     • Tmax · abstract:Tmax = 60 min), showing a high translational value.
121. Other animalRapeseed oleosomes facilitate intestinal lymphatic delivery and oral bioavailability of cannabidiol.
     Int J Pharm, 2025 · Design: not stated · abstract only (PubMed) · open access (hybrid)
     PMID 39550011DOI 10.1016/j.ijpharm.2024.124947
     Verification: abstract-only auto-extract; unverified
122. Other animalQuantitation of Cannabidiol (CBD) in brain regions and plasma following intranasal administration of a CBD nanoformulation.
     J Cannabis Res, 2025 · Design: not stated · n: n = 4 · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 40847324DOI 10.1186/s42238-025-00308-5PMC12372218 (free full text)
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:Plasma, olfactory bulb (OB), hippocampus (HP), striatum (STR), and cortex (CTX) were collected and analyzed for CBD and 7-COOH-CBD using liquid chromatography-mass spectrometry (LC-MS).
     • Key findings · abstract:In plasma, maximum CBD levels were detected at 4 h (797 µg/mL), whereas 7-COOH-CBD peaked at 2 h (893 µg/mL).
     • Key findings · abstract:Despite measurable brain penetration, only 0.12% of the administered dose reached brain tissue, with 15.94% retained in plasma.
     • Key findings · abstract:This study aimed to develop a novel hydrophilic CBD nanoformulation for IN delivery and quantify its distribution and its major metabolite, 7-carboxy-cannabidiol (7CBD-CO[excerpt truncated in our database — see source]
     • Form comparison · full text, Section 'Results':The metabolite of CBD, 7COOH-CBD was statistically highest at 2 h (2606 ± 442) ng/mg in the OB region compared to 4 and 8 h.
123. Other animalPharmacokinetics of cannabidiol and its two main phase I metabolites in Connemara ponies.
     Front Vet Sci, 2025 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 40654508DOI 10.3389/fvets.2025.1599934PMC12247600 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:The pharmacokinetic parameters for CBD were Cmax = 31.472 ± 8.080 ng/mL, tmax = 2.111 ± 0.928 h, t1/2 = 12.563 ± 3.054 h, and Vz/F = 198.757 ± 49.123 L/kg.
     • Cmax · abstract:The pharmacokinetic parameters for CBD were Cmax = 31.472 ± 8.080 ng/mL, tmax = 2.111 ± 0.928 h, t1/2 = 12.563 ± 3.054 h, and Vz/F = 198.757 ± 49.123 L/kg.
     • Tmax · abstract:The pharmacokinetic parameters for CBD were Cmax = 31.472 ± 8.080 ng/mL, tmax = 2.111 ± 0.928 h, t1/2 = 12.563 ± 3.054 h, and Vz/F = 198.757 ± 49.123 L/kg.
     • Cmax · full text, Table 1:ngle oral administration of CBD (2 mg/kg) to 10 horses. Parameter Unit Mean SD n λz h−1 0.059 0.016 10 t1/2 h 12.563 3.054 10 tmax h 2.111 0.928 10 Cmax ng/mL 31.472 8.080 10 AUC 0-t ng/mL*h 182.557 43.524 10 AUC 0-inf ng/mL*h 186.069 43.838 10 MRT 0-inf h 15.868 7.830 10 Vz/F (L/kg) 198.757 49.123 10 Cl/F (L/(kg*h)) 11.235 2.396 10
     • Cmax · full text, Section 'CBD plasma concentration':The mean maximum plasma concentration (Cmax) of CBD and the time to peak concentration (tmax) were 31.472 ± 8.080 ng/mL and 2.111 ± 0.928 h (Figure 1), while the average half-life (t1/2) was 12.563 ± 3.054 h (Table 1).
     • Tmax · full text, Table 1:for CBD following a single oral administration of CBD (2 mg/kg) to 10 horses. Parameter Unit Mean SD n λz h−1 0.059 0.016 10 t1/2 h 12.563 3.054 10 tmax h 2.111 0.928 10 Cmax ng/mL 31.472 8.080 10 AUC 0-t ng/mL*h 182.557 43.524 10 AUC 0-inf ng/mL*h 186.069 43.838 10 MRT 0-inf h 15.868 7.830 10 Vz/F (L/kg) 198.757 49.123 10 Cl/F (L/(kg*h)) 11.235 2.396 10
     • Tmax · full text, Section 'CBD plasma concentration':The mean maximum plasma concentration (Cmax) of CBD and the time to peak concentration (tmax) were 31.472 ± 8.080 ng/mL and 2.111 ± 0.928 h (Figure 1), while the average half-life (t1/2) was 12.563 ± 3.054 h (Table 1).
     • AUC · full text, Table 1:CBD (2 mg/kg) to 10 horses. Parameter Unit Mean SD n λz h−1 0.059 0.016 10 t1/2 h 12.563 3.054 10 tmax h 2.111 0.928 10 Cmax ng/mL 31.472 8.080 10 AUC 0-t ng/mL*h 182.557 43.524 10 AUC 0-inf ng/mL*h 186.069 43.838 10 MRT 0-inf h 15.868 7.830 10 Vz/F (L/kg) 198.757 49.123 10 Cl/F (L/(kg*h)) 11.235 2.396 10
     • Food effect · full text, Section 'Animal treatment':The last feeding of hay occurred 12 h prior to CBD administration, and hay was withheld for an additional 30 min following the administration of the CBD oil; however, the horses had access to straw bedding, which allowed for some foraging, so the fasting period was not absolute.
     • Form comparison · full text, Section 'CBD plasma concentration':Individuals with double CBD concentration peak had minimal lower body weight on average (mean±SD, 490.6 ± 43.0 vs. 486.4 ± 20.2 kg; test statistic = −2.889, p = 0.004), however, the TG level in blood was significantly higher before the CBD administration, 0.531 mmol/L in the simple peak and 0.731 mmol/L in the double peak group (t = −2.518, df. = 13.358, p = 0.025).
     • Form comparison · full text, Section 'CBD plasma concentration':When this data point was considered an outlier and excluded from the analysis, the observed differences were no longer statistically significant (body weight mean±SD: 490.600 ± 43.002 vs. 496.000 ± 6.946 kg (test statistic = −0.854, p = 0.394) and TG mean±SD: 0.531 vs. 0.644 mmol/L (t = −1.8331, df = 13.363, p-value = 0.08916)).
124. Other animalSafety, Efficacy and Doxorubicin Pharmacokinetics During Cannabidiol/Cannabidiolic Acid Rich Hemp Oil Use in Dogs With Lymphoma Undergoing CHOP Chemotherapy.
     J Vet Intern Med, 2025 · Design: randomized; double-blind · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 40622742DOI 10.1111/jvim.70179PMC12232875 (free full text)
     Verification: full text read; no PK numbers matched
     • Key findings · abstract:Primary outcomes evaluated included adverse events during chemotherapy, quality of life scores and doxorubicin area under the curve (AUC) over a 5-week period.
     • Key findings · abstract:The doxorubicin AUC was not different between groups at week 0 [placebo 390.8 nM/h (318.6-479.4);[excerpt truncated in our database — see source]
     • AUC · abstract:Primary outcomes evaluated included adverse events during chemotherapy, quality of life scores and doxorubicin area under the curve (AUC) over a 5-week period.
     • AUC · abstract:The doxorubicin AUC was not different between groups at week 0 [placebo 390.8 nM/h (318.6-479.4);
125. Other animalNovel Lipid Formulation Increases Absorption of Oral Cannabidiol (CBD).
     Pharmaceutics, 2024 · Design: crossover; double-blind · n: n = 1 · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 39771516DOI 10.3390/pharmaceutics16121537PMC11728838 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:Results: Plasma exposure (AUC0-48) of CBD was nine times greater for the lipid formulation than the powder formulation (611.1 ng·h/mL [coefficient of variation {CV%}: 104.6] and 66.8 ng·h/mL [CV%: 50.7], respectively).
     • Key findings · abstract:With the powder formulation, the AUC0-48 was related to the concentration of specific gastrointestinal bacteria and bile acids.
     • AUC · abstract:Results: Plasma exposure (AUC0-48) of CBD was nine times greater for the lipid formulation than the powder formulation (611.1 ng·h/mL [coefficient of variation {CV%}: 104.6] and 66.8 ng·h/mL [CV%: 50.7], respectively).
     • AUC · abstract:With the powder formulation, the AUC0-48 was related to the concentration of specific gastrointestinal bacteria and bile acids.
     • Food effect · abstract:Methods: In a double-blind crossover study in fasting healthy volunteers, we compared the pharmacokinetics of a single dose of 1000 mg of CBD in the lipid formulation and in a powder formulation (ClinicalTrials.gov: NCT05032807).
     • Cmax · full text, Section '6.1.1. Lipid Formulation':The peak concentration (Cmax) of CBD was 198 ng/mL at 1-h post-drug administration (Tmax).
     • Cmax · full text, Section '6.2.2. Aqueous Formulation':The Tmax (1 h) and Cmax (59.5 μg/g of tissue) in the stomach with the aqueous formulation treatment differed markedly from those for the lipid formulation (Tmax = 0 min;
     • Cmax · full text, Section '6.2.2. Aqueous Formulation':Cmax = 2514 μg/g of tissue, extrapolated value).
     • Tmax · full text, Section '4.1. Pharmacokinetics of CBD and Metabol':The tmax was 4 h for the lipid formulation and 6 h for the powder formulation.
     • Tmax · full text, Section '6.1.1. Lipid Formulation':The peak concentration (Cmax) of CBD was 198 ng/mL at 1-h post-drug administration (Tmax).
     • Tmax · full text, Section '6.2.1. Lipid Formulation':For most organs, the Tmax was 1 h post-drug administration (Table 4).
     • AUC · full text, Section '6.1.1. Lipid Formulation':The AUC0–8 was 335 ng/mL·h and the AUC∞ was 381 ng/mL.
     • Food effect · full text, Section '4. Results—Study 1':For all sessions that were tested (n = 21; 13 participants), fasting status was confirmed by the concentration of serum bile acids being within the normal fasting reference range (1–9 μmol/L [31,36].
     • Form comparison · full text, Section '4.2. Safety, Tolerability and Adverse Ev':At 24 h post-treatment, treatment with the lipid formulation was associated with a mean rating of 1.43 for diarrhoea (SD: 0.89), compared to 1.00 (SD: 0.0) for the powder formulation, as measured by GSRS (Supplementary Table S4).
     • Form comparison · full text, Section '4.2. Safety, Tolerability and Adverse Ev':At 48 h post-treatment, treatment with the lipid formulation was associated with a rating of 1.09 (SD: 0.18) for gastrointestinal symptoms overall, versus 1.02 (SD: 0.04) for the powder formulation.
126. Other animalKey Transdermal Patch Using Cannabidiol-Loaded Nanocarriers with Better Pharmacokinetics in vivo.
     Int J Nanomedicine, 2024 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 38770103DOI 10.2147/IJN.S455032PMC11104392 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:RESULTS: In the transdermal application of CTD-12, the relative bioavailability of the formulation was 3.68 ± 0.17-fold greater than in the free CBD application.
     • Key findings · abstract:Moreover, PCTD-12 indicated 2.46 ± 0.18-fold higher relative bioavailability comparing with free CBD patch in the ex vivo evaluation.
     • Key findings · abstract:Most importantly, in the pharmacokinetics of PCTD-12, the relative bioavailability of PCTD-12 was 9.47 ± 0.88-fold higher than in the oral application.
     • Relative bioavailability · abstract:RESULTS: In the transdermal application of CTD-12, the relative bioavailability of the formulation was 3.68 ± 0.17-fold greater than in the free CBD application.
     • Relative bioavailability · abstract:Moreover, PCTD-12 indicated 2.46 ± 0.18-fold higher relative bioavailability comparing with free CBD patch in the ex vivo evaluation.
     • Relative bioavailability · abstract:Most importantly, in the pharmacokinetics of PCTD-12, the relative bioavailability of PCTD-12 was 9.47 ± 0.88-fold higher than in the oral application.
     • AUC · full text, Table 1:± 2.35 Permeation ratio (%) 6.7 ± 0.09 7.48 ± 0.13 21.9 ± 0.19 35.21 ± 2.01 Flux0–24hr(mcg/hr∙cm2) 15.8 ± 0.21 17.64 ± 0.31 51.66 ± 0.44 83.07 ± 4.74 AUC0-24hr(mcg∙hr) 10,234.09 ± 195.88 12,518.72 ± 160.11 24,886.41 ± 403.14 37,647.43 ± 1696.35 0–24 hr Relative FA (fold) 1 1.22 ± 0.02 2.43 ± 0.04 3.68 ± 0.17
     • Relative bioavailability · full text, Section 'Development and Characterization of CBD ':For the sample preparation of TEM imaging, the CTD were diluted 10-fold with 2%wt phosphotungstic acid.
127. Other animalPharmacokinetic of two oral doses of a 1:20 THC:CBD cannabis herbal extract in cats.
     Front Vet Sci, 2024 · Design: not stated · n: n = 6 · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 38585296DOI 10.3389/fvets.2024.1352495PMC10996858 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:Plasma samples were analyzed for CBD, THC, and metabolites 6-OH-CBD, 7-OH-CBD, 11-OH-THC, and THC-COOH using a previously validated LC-MS/MS method.
     • Key findings · abstract:RESULTS: CBD and THC were quickly absorbed (mean Tmax of 2.4-2.9 h).
     • Key findings · abstract:Maximum plasma concentrations (Cmax) ranged from 36-511 ng/mL and 6.8-61 ng/mL for CBD and THC, respectively.
     • Key findings · abstract:Dose-adjusted Cmax and AUC0-last values were not statistically significantly different (p > 0.05) between dose groups indicating CBD and THC concentrations increased in a manner proportional (linear) to the dose.
     • Key findings · abstract:Dose-adjusted THC Cmax and AUC0-last were significa[excerpt truncated in our database — see source]
     • Cmax · abstract:Maximum plasma concentrations (Cmax) ranged from 36-511 ng/mL and 6.8-61 ng/mL for CBD and THC, respectively.
     • Cmax · abstract:Dose-adjusted Cmax and AUC0-last values were not statistically significantly different (p > 0.05) between dose groups indicating CBD and THC concentrations increased in a manner proportional (linear) to the dose.
     • Cmax · abstract:Dose-adjusted THC Cmax and AUC0-last were significantly higher than the corresponding dose-adjusted CBD parameters (p < 0.01).
     • Tmax · abstract:RESULTS: CBD and THC were quickly absorbed (mean Tmax of 2.4-2.9 h).
     • AUC · abstract:Dose-adjusted Cmax and AUC0-last values were not statistically significantly different (p > 0.05) between dose groups indicating CBD and THC concentrations increased in a manner proportional (linear) to the dose.
     • AUC · abstract:Dose-adjusted THC Cmax and AUC0-last were significantly higher than the corresponding dose-adjusted CBD parameters (p < 0.01).
     • Fractional absorption · abstract:RESULTS: CBD and THC were quickly absorbed (mean Tmax of 2.4-2.9 h).
     • Food effect · abstract:METHODS: Single-dose PK were assessed after oral administration of CHE at low or high dose (2 mg CBD + 0.1 mg THC, or 5 mg CBD + 0.25 mg THC per kg bw, respectively; n = 6 per group) in fasting cats.
     • Cmax · full text, Table 2:Domestic Shorthair cats (n = 6/dose group) receiving a single oral dose of 1:20 THC:CBD CHE at 2 or 5 mg CBD/kg bw. Cannabinoid Dose (mg/kg) Tmax (h) Cmax (ng/mL) Dose-Adj. Cmax (ng/mL per mg/kg dose)a T1/2 β (h)b T1/2 λ (h)c AUC0-last (ng*h/mL) Dose-Adj. AUC0-last (ng*h/mL per mg/kg)a CBD 2 2.4 (0.7) 111.2 (79.0) 55.6 (39.5) 2.9 (2.0) 7.7 (1.0) 344 (183) 170.8 (91.4) 5 2.5 (0.8) 214.1 (182.8) 42.
     • Tmax · full text, Table 2:n fasted Domestic Shorthair cats (n = 6/dose group) receiving a single oral dose of 1:20 THC:CBD CHE at 2 or 5 mg CBD/kg bw. Cannabinoid Dose (mg/kg) Tmax (h) Cmax (ng/mL) Dose-Adj. Cmax (ng/mL per mg/kg dose)a T1/2 β (h)b T1/2 λ (h)c AUC0-last (ng*h/mL) Dose-Adj. AUC0-last (ng*h/mL per mg/kg)a CBD 2 2.4 (0.7) 111.2 (79.0) 55.6 (39.5) 2.9 (2.0) 7.7 (1.0) 344 (183) 170.8 (91.4) 5 2.5 (0.8) 214.1 (1
     • AUC · full text, Table 2::20 THC:CBD CHE at 2 or 5 mg CBD/kg bw. Cannabinoid Dose (mg/kg) Tmax (h) Cmax (ng/mL) Dose-Adj. Cmax (ng/mL per mg/kg dose)a T1/2 β (h)b T1/2 λ (h)c AUC0-last (ng*h/mL) Dose-Adj. AUC0-last (ng*h/mL per mg/kg)a CBD 2 2.4 (0.7) 111.2 (79.0) 55.6 (39.5) 2.9 (2.0) 7.7 (1.0) 344 (183) 170.8 (91.4) 5 2.5 (0.8) 214.1 (182.8) 42.8 (36.6) 2.5 (0.4) 17.1 (5.8) 1,293 (970) 258.6 (194.0) Combined CBD dose gr
     • Food effect · full text, Table 1:Mean ± S.D. concentrations of CBD and THC in plasma for fasted Domestic Shorthair cats administered a single dose of CHE (n = 6 per dose group). Time (h) Low dose (2 mg CBD + 0.1 mg THC/kg bw) High dose (5 mg CBD + 0.25 mg THC/kg bw) CBD (ng/mL) THC (ng/mL) THC:CBD ratio CBD (ng/mL) THC (ng/mL) THC:CBD ratio 0.
     • Food effect · full text, Table 2:Mean (SD) cannabinoid PK parameters in fasted Domestic Shorthair cats (n = 6/dose group) receiving a single oral dose of 1:20 THC:CBD CHE at 2 or 5 mg CBD/kg bw. Cannabinoid Dose (mg/kg) Tmax (h) Cmax (ng/mL) Dose-Adj. Cmax (ng/mL per mg/kg dose)a T1/2 β (h)b T1/2 λ (h)c AUC0-last (ng*h/mL) Dos
128. Other animalPharmacokinetics and tolerability of single-dose enteral cannabidiol and cannabidiolic acid rich hemp in horses (Equus caballus).
     Front Vet Sci, 2024 · Design: randomized; crossover · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 38681854DOI 10.3389/fvets.2024.1356463PMC11047043 (free full text)
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:Serial serum samples collected over 48 h were analyzed by high performance liquid chromatography with tandem mass spectrometry.
     • Key findings · abstract:Plasma chemistry analysis was performed at 0 h and 24 h.
     • Key findings · abstract:The median half-life of elimination was not calculated for the 2 mg/kg CBD treatment due to lack of time points above the lower quantifiable limit beyond the Cmax while it was 7.75 h in the 8 mg/kg group.
     • Cmax · abstract:The median half-life of elimination was not calculated for the 2 mg/kg CBD treatment due to lack of time points above the lower quantifiable limit beyond the Cmax while it was 7.75 h in the 8 mg/kg group.
     • Cmax · full text, Table 1:Median (95% CI) pharmacokinetic parameters after enteral dosing of CBD/CBDA-rich hemp oil in horses using a non-compartmental model. Analyte Cmax Tmax T0.5Elim AUC MRT CBD (2 mg/kg) 5.2 (2.93–8.95) 3.0 (1.52–5.48) NA 44 (26.52–66.34) NA CBD (8 mg/kg) 40.35 (27.70–52.17) 8.0 (4.16–10.34) 8.3 * (6.37–8.93) 501.5 (343.25–687.50) 12.6 (10.29–14.16) THC (8 mg/kg) 6.65 (5.52–8.25) 6.0 (3.54–9.96) N
     • Cmax · full text, Section 'Pharmacokinetics':CBDA was measurable for pharmacokinetic assessment in both the 2 and 8 mg/kg group however due to a biphasic curve a Tmax1/Tmax 2 and Cmax1 and Cmax 2 are reported as well as AUC and MRT (Table 2).
     • Cmax · full text, Section 'Pharmacokinetics':The major metabolite 7-COOH-CBD Cmax was at 12 h for both the 2 mg/kg and 8 mg/kg group at 133.7 mg/mL and 777.5 ng/mL, respectively.
     • Tmax · full text, Table 1:Median (95% CI) pharmacokinetic parameters after enteral dosing of CBD/CBDA-rich hemp oil in horses using a non-compartmental model. Analyte Cmax Tmax T0.5Elim AUC MRT CBD (2 mg/kg) 5.2 (2.93–8.95) 3.0 (1.52–5.48) NA 44 (26.52–66.34) NA CBD (8 mg/kg) 40.35 (27.70–52.17) 8.0 (4.16–10.34) 8.3 * (6.37–8.93) 501.5 (343.25–687.50) 12.6 (10.29–14.16) THC (8 mg/kg) 6.65 (5.52–8.25) 6.0 (3.54–9.96) NA 98.
     • Tmax · full text, Section 'Pharmacokinetics':Due to a later than expected T max (8 h) T0.5 elim and MRT were based on 6 of 8 horses with sufficient data points for analysis and are thus reported.
     • Tmax · full text, Section 'Pharmacokinetics':CBDA was measurable for pharmacokinetic assessment in both the 2 and 8 mg/kg group however due to a biphasic curve a Tmax1/Tmax 2 and Cmax1 and Cmax 2 are reported as well as AUC and MRT (Table 2).
     • AUC · full text, Table 1:% CI) pharmacokinetic parameters after enteral dosing of CBD/CBDA-rich hemp oil in horses using a non-compartmental model. Analyte Cmax Tmax T0.5Elim AUC MRT CBD (2 mg/kg) 5.2 (2.93–8.95) 3.0 (1.52–5.48) NA 44 (26.52–66.34) NA CBD (8 mg/kg) 40.35 (27.70–52.17) 8.0 (4.16–10.34) 8.3 * (6.37–8.93) 501.5 (343.25–687.50) 12.6 (10.29–14.16) THC (8 mg/kg) 6.65 (5.52–8.25) 6.0 (3.54–9.96) NA 98.0 (70.74–1
     • AUC · full text, Table 2:meters of CBDA and THCA after enteral dosing of CBD/CBDA-rich hemp oil in horses using a non-compartmental model. Analyte CmaxP1 TmaxP1 CmaxP2 TmaxP2 AUC MRT CBDA (2 mg/kg) 20.05 (4.14–69.76) 0.5 (0.24–1.13) 17.7 (10.12–28.97) 8.0 (4.53–10.05) 410.5 (289.53–560.97) 12.8 (11.49–14.14) CBDA (8 mg/kg) 312.2 (92.67–614.45) 0.5 (0.43–1.07) 164.45 (115.88–251.54) 4.0 (3.54–7.21) 3,353 (2,753.3–4,006.7)
     • AUC · full text, Section 'Pharmacokinetics':CBDA was measurable for pharmacokinetic assessment in both the 2 and 8 mg/kg group however due to a biphasic curve a Tmax1/Tmax 2 and Cmax1 and Cmax 2 are reported as well as AUC and MRT (Table 2).
     • Food effect · full text, Section 'Animals':During the study period, horses were allowed free access to water and coastal Bermuda hay and fed a proprietary pelleted feed once per day in the morning, approximately 2 h prior to treatment.
     • Form comparison · full text, Section 'Vital parameters, hematology and blood c':Median blood urea nitrogen was significantly decreased at 24 h post-dosing (17.5 mg/dL, 95% CI 16.0–18.7) in the 2 mg/kg CBD group compared to the pre-dosing time 0 sample (20.5 g/dL, 95% CI 18.0–21.8; p = 0.016).
     • Form comparison · full text, Section 'Vital parameters, hematology and blood c':Median glucose was significantly increased at 24 h post-dosing (108 mg/dL, 95% CI 97.8–121.9) in the 8 mg/kg CBD group compared to the pre-dosing time 0 sample (90 mg/dL, 95% CI 85.9–97.4; p = 0.003).
     • Form comparison · full text, Section 'Vital parameters, hematology and blood c':Median bicarbonate was significantly decreased at 24 h post-dosing (31 mEq/L, 95% CI 29.9–31.1) in the 8 mg/kg CBD group compared to pre-dosing time 0 sample (32 mEq/L, 95% CI 31.2–32.3; p = 0.0018).
129. Other animalPharmacokinetics behavior of four cannabidiol preparations following single oral administration in dogs.
     Front Vet Sci, 2024 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 38725584DOI 10.3389/fvets.2024.1389810PMC11080651 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:However, the CBD in all preparations reached the maximum plasma concentration within 3 h post-dose, with an average range of 92-314 μg/L.
     • Cmax · full text, Section 'Results':However, the highest Cmax of the CBD in the plasma (314.30 ± 81.09 μg/L) was obtained from administration of the WM group, while the lowest Cmax of the CBD in the plasma was in the CM group (92.29 ± 21.45 μg/L).
     • Cmax · full text, Section 'Results':Among the preparations, there was rapid absorption in the NM group, with peak plasma concentrations occurring within 2 h after ingestion.
     • Cmax · full text, Section 'Results':In contrast, only three of the eight dogs in the CM group achieved a Cmax over 100 μg/L.
     • Relative bioavailability · full text, Section 'Results':The relative bioavailability levels after dose-normalization of the other formulations comparing to the OM formulation were 80.9, 59.5, and 34.8% for the WM, NM and CM groups, respectively.
130. Other animalCannabidiol promotes intestinal cholesterol uptake mediated by Pregnane X receptor.
     Front Endocrinol (Lausanne), 2024 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 38957441DOI 10.3389/fendo.2024.1398462PMC11217338 (free full text)PDF
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     • Key findings · abstract:The C57BL/6 wildtype mice were orally fed CBD in the presence of PXR antagonist resveratrol (RES) to determine how CBD exposure could change the plasma lipid profiles in a PXR-dependent manner.
     • Food effect · abstract:The C57BL/6 wildtype mice were orally fed CBD in the presence of PXR antagonist resveratrol (RES) to determine how CBD exposure could change the plasma lipid profiles in a PXR-dependent manner.
     • Food effect · full text, Section 'Animals':To determine the optimal CBD dose that could activate PXR signaling in mice with the minimal toxicity, we fed the mice with CBD at the dose of 3 and 10 mg/kg body weight per day by oral gavage for 7 days on chow diet (3 mice/group).
     • Food effect · full text, Section 'Animals':RES at 45 mg/kg significantly improved osteoarthritis symptoms in mice (46), and the diet-induced obesity mice fed RES by gavage (75 mg/kg) did not show hepatic toxicity (47).
     • Food effect · full text, Section 'Animals':To establish the optimal dose of PXR antagonist RES, we fed the mice (3 mice/group) by oral gavage with CBD at a dose of 10 mg/kg BW daily together with the two different doses of RES (45 and 75 mg/kg/day).
131. Other animalPharmacokinetic modelling of orally administered cannabidiol and implications for medication control in horses.
     Front Vet Sci, 2023 · Design: not stated · n: n = 3 · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 37621871DOI 10.3389/fvets.2023.1234551PMC10445762 (free full text)
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     • Key findings · abstract:AUC0-12 h and Cmax were tested for dose proportionality.
     • Key findings · abstract:High volumes of distribution into peripheral compartments and high concentrations of 7-carboxy-CBD were observed in serum.
     • Key findings · abstract:Non-compartmental analysis identified a Cmax of 12.17 ± 2.08 ng/mL after single administration of CBD (dose: 3 mg/kg).
     • Key findings · abstract:AUC0-12 h showed dose proportionality, increase for Cmax leveled off at higher doses.
     • Key findings · abstract:Following multiple doses, the CBD terminal half-life was 161.29 ± 43.65 h in serum.
     • Cmax · abstract:AUC0-12 h and Cmax were tested for dose proportionality.
     • Cmax · abstract:Non-compartmental analysis identified a Cmax of 12.17 ± 2.08 ng/mL after single administration of CBD (dose: 3 mg/kg).
     • Cmax · abstract:AUC0-12 h showed dose proportionality, increase for Cmax leveled off at higher doses.
     • AUC · abstract:AUC0-12 h and Cmax were tested for dose proportionality.
     • AUC · abstract:AUC0-12 h showed dose proportionality, increase for Cmax leveled off at higher doses.
     • Cmax · full text, Table 3:st trial (0.2 mg/kg, n = 3) Second trial (1 mg/kg, n = 3) Third trial (3 mg/kg, n = 5) CBD AUC0–12 h (h·ng/mL) 4.45 ± 2.52 15.46 ± 6.08 59.53 ± 13.54 Cmax (ng/mL) 1.98 ± 0.99 2.58 ± 1.25 12.17 ± 2.08 tmax (hr) 1 ± 0 1 ± 0 1.1 ± 0.55 7-COOH-CBD AUC0–12 h (h·ng/mL) 106.95 ± 65.68 571.02 ± 194.33 1768.38 ± 450.86 Ratio: AUC0−12h(7−COOH−CBD)AUC0−12h(CBD) 21.09 ± 3.19(2109.15%) 38.78 ± 7.82(3877.88%)
     • Cmax · full text, Table 5:First trial (0.2 mg/kg, n = 3) Second trial (1 mg/kg, n = 3) Third trial (3 mg/kg, n = 5) AUC0–12 h (h·ng/mL) 4.99 ± 1.56 13.64 ± 5.33 58.56 ± 12.98 Cmax (ng/mL) 1.82 ± 0.83 3.10 ± 1.27 14.61 ± 5.08 tmax (hr) 1.01 ± 0.01 1.02 ± 0.03 1.02 ± 0.01 Ratio: Parameter(CBDPop_PK)Parameter(CBDNCA) AUC0−12h(CBDPop_PK)AUC0−12h(CBDNCA) 1.20 ± 0.24 0.86 ± 0.11 0.98 ± 0.09 Cmax(CBDPop_PK)Cmax(CBDNCA)
     • Cmax · full text, Section 'Dose proportionality':Pharmacokinetic parameters AUC0–12 h and Cmax for CBD were tested for dose proportionality using the individual values obtained from NCA and population pharmacokinetic analysis during the dose escalation study.
     • Tmax · full text, Table 3:n = 3) Third trial (3 mg/kg, n = 5) CBD AUC0–12 h (h·ng/mL) 4.45 ± 2.52 15.46 ± 6.08 59.53 ± 13.54 Cmax (ng/mL) 1.98 ± 0.99 2.58 ± 1.25 12.17 ± 2.08 tmax (hr) 1 ± 0 1 ± 0 1.1 ± 0.55 7-COOH-CBD AUC0–12 h (h·ng/mL) 106.95 ± 65.68 571.02 ± 194.33 1768.38 ± 450.86 Ratio: AUC0−12h(7−COOH−CBD)AUC0−12h(CBD) 21.09 ± 3.19(2109.15%) 38.78 ± 7.82(3877.88%) 31.02 ± 6.38(3102.13%) 7-OH-CBD AUC0–12 h (h·ng/mL
     • Tmax · full text, Table 5:/kg, n = 3) Third trial (3 mg/kg, n = 5) AUC0–12 h (h·ng/mL) 4.99 ± 1.56 13.64 ± 5.33 58.56 ± 12.98 Cmax (ng/mL) 1.82 ± 0.83 3.10 ± 1.27 14.61 ± 5.08 tmax (hr) 1.01 ± 0.01 1.02 ± 0.03 1.02 ± 0.01 Ratio: Parameter(CBDPop_PK)Parameter(CBDNCA) AUC0−12h(CBDPop_PK)AUC0−12h(CBDNCA) 1.20 ± 0.24 0.86 ± 0.11 0.98 ± 0.09 Cmax(CBDPop_PK)Cmax(CBDNCA) 0.92 ± 0.08 1.21 ± 0.21 1.18 ± 0.29 tmax(CBDPop
     • Tmax · full text, Section 'Dose escalation study':Table 3 presents the parameters AUC0–12 h, Cmax and tmax assessed in the NCA and the AUC0–12 h ratio between CBD and its metabolites 7-OH-CBD and 7-COOH-CBD.
     • AUC · full text, Table 3:ring dose escalation study, derived from NCA. Parameter First trial (0.2 mg/kg, n = 3) Second trial (1 mg/kg, n = 3) Third trial (3 mg/kg, n = 5) CBD AUC0–12 h (h·ng/mL) 4.45 ± 2.52 15.46 ± 6.08 59.53 ± 13.54 Cmax (ng/mL) 1.98 ± 0.99 2.58 ± 1.25 12.17 ± 2.08 tmax (hr) 1 ± 0 1 ± 0 1.1 ± 0.55 7-COOH-CBD AUC0–12 h (h·ng/mL) 106.95 ± 65.68 571.02 ± 194.33 1768.38 ± 450.86 Ratio: AUC0−12h(7−COOH−CBD)A
     • AUC · full text, Table 5:e individual fits of the population pharmacokinetic model. First trial (0.2 mg/kg, n = 3) Second trial (1 mg/kg, n = 3) Third trial (3 mg/kg, n = 5) AUC0–12 h (h·ng/mL) 4.99 ± 1.56 13.64 ± 5.33 58.56 ± 12.98 Cmax (ng/mL) 1.82 ± 0.83 3.10 ± 1.27 14.61 ± 5.08 tmax (hr) 1.01 ± 0.01 1.02 ± 0.03 1.02 ± 0.01 Ratio: Parameter(CBDPop_PK)Parameter(CBDNCA) AUC0−12h(CBDPop_PK)AUC0−12h(CBDNCA) 1.20 ± 0
     • AUC · full text, Section 'Dose proportionality':Pharmacokinetic parameters AUC0–12 h and Cmax for CBD were tested for dose proportionality using the individual values obtained from NCA and population pharmacokinetic analysis during the dose escalation study.
132. Other animalPharmacokinetics and oral bioavailability of cannabidiol in horses after intravenous and oral administration with oil and micellar formulations.
     Equine Vet J, 2023 · Design: randomized · n: 8 horses · abstract only (PubMed) · closed/paywalled
     PMID 36624043DOI 10.1111/evj.13923
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:Oral bioavailability was close to 14% for both oral administrations.
     • Key findings · abstract:Simulated dose regimen of CBD every 12 and 24 h predicted similar percentages to reach effective plasma concentration with both oral formulation at 10.00 mg/kg.
133. Other animalComparative Pharmacokinetics of Commercially Available Cannabidiol Isolate, Broad-Spectrum, and Full-Spectrum Products.
     Eur J Drug Metab Pharmacokinet, 2023 · Design: not stated · abstract only (PubMed) · closed/paywalled
     PMID 37337087DOI 10.1007/s13318-023-00839-3
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:RESULTS: There was an increase in the oral bioavailability of CBD (12% and 21% in male and female rats, respectively) when administered as a full-spectrum product compared with the isolate and broad-spectrum products.
     • Key findings · abstract:There was no difference in the bioavailability of CBD between the commercially available full-spectrum formulation (3.1% CBD; containing 0.2% THC plus terpenes and other minor cannabinoids) versus the in-house preparation of CBD full-spectrum (CBD isolate 3.2% plus 0.2% THC isolate).
     • Key findings · abstract:CONCLUSIONS: The presence of 0.2% THC increased the oral bioavailability of CBD in male and f[excerpt truncated in our database — see source]
134. Other animalCannabidiol plasma determination and pharmacokinetics conducted at beginning, middle and end of long-term supplementation of a broad-spectrum hemp oil to healthy adult dogs.
     Front Vet Sci, 2023 · Design: randomized · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 37841465DOI 10.3389/fvets.2023.1279926PMC10571049 (free full text)PDF
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     • Key findings · abstract:Blood was collected once every 4 weeks pre- and postprandially for CBD plasma determination (at 0 and 2 h).
     • Key findings · abstract:Pharmacokinetics and monthly CBD plasma data of dogs who received CBD were analyzed as repeated measures over time using a mixed model, with significance at α = 0.05.
     • Key findings · abstract:RESULTS: Average plasma CBD at 5 and 10 mg/kg were 97.3 ng/mL and 236.8 ng/mL pre-prandial, 341 ng/mL and 1,068 ng/mL postprandial, respectively.
     • Key findings · abstract:PK parameters suggested CBD accumulation over time, with significant increases in Cmax and AUC at both the 18 and 36-week timepoints.
     • Key findings · abstract:CONCLUSIONS AND CLINICAL IMPORTANCE:[excerpt truncated in our database — see source]
     • Cmax · abstract:PK parameters suggested CBD accumulation over time, with significant increases in Cmax and AUC at both the 18 and 36-week timepoints.
     • AUC · abstract:PK parameters suggested CBD accumulation over time, with significant increases in Cmax and AUC at both the 18 and 36-week timepoints.
     • Food effect · abstract:Blood was collected once every 4 weeks pre- and postprandially for CBD plasma determination (at 0 and 2 h).
     • Food effect · abstract:RESULTS: Average plasma CBD at 5 and 10 mg/kg were 97.3 ng/mL and 236.8 ng/mL pre-prandial, 341 ng/mL and 1,068 ng/mL postprandial, respectively.
     • Cmax · full text, Table 1:CBD (n = 6) once daily for 36 weeks. Week 0 Week 18 Week 36 P P Treatment 5 mg/kg 10 mg/kg 5 mg/kg 10 mg/kg 5 mg/kg 10 mg/kg (Treatment) (Time) Cmax, ng/mL 441bx[284, 686] 880ax[566, 1,369] 585by[376, 909] 1,709ay[1,099, 2,657] 616by[396, 957] 1,746ay[1,123, 2,714] 0.003 0.005 CmaxD, kg*ng/mL/mg 88.2x[56.8, 137.2] 88.0x[56.6, 136.9] 116.9y[75.2, 181.8] 170.9y[109.9, 265.7] 123.1z[79.2, 191.4]
     • Cmax · full text, Section 'Pharmacokinetics':These included time to reach maximum CBD peak (Cmax), time to reach maximum CBD peak normalized by dose (CmaxD), time at which CBD reached its peak (Tmax), half-life or the time it took for plasma CBD concentration to be reduced to half of its peak (T1/2), area under the curve from 0 to 48 h or total CBD exposure within this time frame (AUC0-48h), area under the curve from 0 to 48 h normalized by
     • Cmax · full text, Section 'Pharmacokinetics':Cannabidiol Cmax was approximately twice as high in 10 versus 5 mg/kg dose treatment group when administered to naïve dogs, and nearly 3-fold greater in 10 vs. 5 mg/kg at weeks 18 and 36 [Table 1;
     • Tmax · full text, Section 'Pharmacokinetics':These included time to reach maximum CBD peak (Cmax), time to reach maximum CBD peak normalized by dose (CmaxD), time at which CBD reached its peak (Tmax), half-life or the time it took for plasma CBD concentration to be reduced to half of its peak (T1/2), area under the curve from 0 to 48 h or total CBD exposure within this time frame (AUC0-48h), area under the curve from 0 to 48 h normalized by
     • AUC · full text, Table 1:maxD, kg*ng/mL/mg 88.2x[56.8, 137.2] 88.0x[56.6, 136.9] 116.9y[75.2, 181.8] 170.9y[109.9, 265.7] 123.1z[79.2, 191.4] 174.6z[112.3, 271.4] 0.342 0.005 AUC0-48h, h*ng/mL 3,525bx[2,650, 4,690] 6,930ax[5,209, 9,220] 7,205by[5,415, 9,586] 18,033ay[13,554, 23,992] 9,346bz[7,025, 12,434] 22,138az[16,640, 29,454] 0.001 <0.0001 AUCD0-48h, hr.*kg*ng/ml/mg 705x[530, 938] 693x[521, 922] 1,441y[1,083, 1917] 1,
     • AUC · full text, Section 'Pharmacokinetics':These included time to reach maximum CBD peak (Cmax), time to reach maximum CBD peak normalized by dose (CmaxD), time at which CBD reached its peak (Tmax), half-life or the time it took for plasma CBD concentration to be reduced to half of its peak (T1/2), area under the curve from 0 to 48 h or total CBD exposure within this time frame (AUC0-48h), area under the curve from 0 to 48 h normalized by
     • AUC · full text, Section 'Pharmacokinetics':Likewise, AUC0-48h at week 0 was approximately twice as high in dogs given 10 mg/kg vs. 5 mg/kg, and this difference increased over time [P (Treatment) = 0.001 and P (Time) < 0.0001].
     • Relative bioavailability · full text, Section 'Pharmacokinetics':Cannabidiol Cmax was approximately twice as high in 10 versus 5 mg/kg dose treatment group when administered to naïve dogs, and nearly 3-fold greater in 10 vs. 5 mg/kg at weeks 18 and 36 [Table 1;
     • Form comparison · full text, Section 'Pharmacokinetics':Cannabidiol Cmax was approximately twice as high in 10 versus 5 mg/kg dose treatment group when administered to naïve dogs, and nearly 3-fold greater in 10 vs. 5 mg/kg at weeks 18 and 36 [Table 1;
     • Form comparison · full text, Section 'Pharmacokinetics':Likewise, AUC0-48h at week 0 was approximately twice as high in dogs given 10 mg/kg vs. 5 mg/kg, and this difference increased over time [P (Treatment) = 0.001 and P (Time) < 0.0001].
135. Other animalTherapeutic efficacy and pharmacokinetics of liposomal-cannabidiol injection: a pilot clinical study in dogs with naturally-occurring osteoarthritis.
     Front Vet Sci, 2023 · Design: not stated · n: 6 dogs · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 37680386DOI 10.3389/fvets.2023.1224452PMC10481162 (free full text)PDF
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     • Key findings · abstract:RESULTS: CBD plasma concentrations were observed for 6 weeks; median (range) peak plasma concentration (Cmax) was 45.2 (17.8-72.5) ng/mL, time to Cmax was 4 (2-14) days and half-life was 12.4 (7.7-42.6) days.
     • Key findings · abstract:CONCLUSION: Liposomal-CBD administered subcutaneously produced detectable CBD plasma concentrations for 6 weeks with minimal side effects and demonstrated reduced pain and increased wellbeing as part of multimodal pain management in dogs suffering from osteoarthritis.
     • Cmax · abstract:RESULTS: CBD plasma concentrations were observed for 6 weeks; median (range) peak plasma concentration (Cmax) was 45.2 (17.8-72.5) ng/mL, time to Cmax was 4 (2-14) days and half-life was 12.4 (7.7-42.6) days.
     • Cmax · full text, Table 2:Pharmacokinetic data of plasma cannabidiol (CBD) from six dogs with osteoarthritis after a single subcutaneous 5 mg/kg liposomal-CBD injection. Dog Cmax (ng/mL) C21 days (ng/mL) C42 days (ng/mL) Tmax (days) Half-life (days) AUC (ng·h/mL) AUC/dose (ng·h/mL/mg/kg) 1 17.8 7.5 4.3 14 42.6 9,810 1962 2 44.8 1.5 0.9 4 10.5 11,877 2,375 3 45.7 3.4 0.4 2 7.7 11,630 2,326 4 49.4 2.1 0.8 7 12.1# 12,380 2,47
     • Cmax · full text, Section 'Pharmacokinetics':Compared with various oral CBD-containing formulations administering a single 2 mg/kg dose in dogs, the median/mean Cmax, Tmax, and half-life were 102.3 ng/mL, 1.5 h, and 4.2 h, respectively (n = 4) (17); 213 ng/mL, 2.1 h, and 2.5 h, respectively (n = 6) (11); 301 ng/mL, 1.4 h, and 1.0 h, respectively, (22); 226 ng/mL, 2.5 h, and 3.8 h, respectively (34).
     • Cmax · full text, Section 'Pharmacokinetics':Mean Cmax and Tmax for OTM and oral routes were 200.3 ng/mL and 1.9 h, and 206.8 ng/mL and 2.2 h, respectively.
     • Tmax · full text, Table 2:BD) from six dogs with osteoarthritis after a single subcutaneous 5 mg/kg liposomal-CBD injection. Dog Cmax (ng/mL) C21 days (ng/mL) C42 days (ng/mL) Tmax (days) Half-life (days) AUC (ng·h/mL) AUC/dose (ng·h/mL/mg/kg) 1 17.8 7.5 4.3 14 42.6 9,810 1962 2 44.8 1.5 0.9 4 10.5 11,877 2,375 3 45.7 3.4 0.4 2 7.7 11,630 2,326 4 49.4 2.1 0.8 7 12.1# 12,380 2,476 5 72.5 5.7 5.9 4 12.8# 19,275 3,855 6 37.7
     • Tmax · full text, Section 'Pharmacokinetics':Compared with various oral CBD-containing formulations administering a single 2 mg/kg dose in dogs, the median/mean Cmax, Tmax, and half-life were 102.3 ng/mL, 1.5 h, and 4.2 h, respectively (n = 4) (17); 213 ng/mL, 2.1 h, and 2.5 h, respectively (n = 6) (11); 301 ng/mL, 1.4 h, and 1.0 h, respectively, (22); 226 ng/mL, 2.5 h, and 3.8 h, respectively (34).
     • Tmax · full text, Section 'Pharmacokinetics':Mean Cmax and Tmax for OTM and oral routes were 200.3 ng/mL and 1.9 h, and 206.8 ng/mL and 2.2 h, respectively.
     • AUC · full text, Table 2:rthritis after a single subcutaneous 5 mg/kg liposomal-CBD injection. Dog Cmax (ng/mL) C21 days (ng/mL) C42 days (ng/mL) Tmax (days) Half-life (days) AUC (ng·h/mL) AUC/dose (ng·h/mL/mg/kg) 1 17.8 7.5 4.3 14 42.6 9,810 1962 2 44.8 1.5 0.9 4 10.5 11,877 2,375 3 45.7 3.4 0.4 2 7.7 11,630 2,326 4 49.4 2.1 0.8 7 12.1# 12,380 2,476 5 72.5 5.7 5.9 4 12.8# 19,275 3,855 6 37.7 1.6 2.0 2 14.7# 4,529 906 Med
     • AUC · full text, Section 'Pharmacokinetics':When normalized to dose, the AUC following liposomal-CBD administration in the present study (2,351 ng·h/mL/mg/kg;
     • Food effect · full text, Section 'Pharmacokinetics':In people, bioavailability of CBD is very low (6%–10%) and depends on fasting conditions (21).
     • Form comparison · full text, Section 'Pharmacokinetics':Compared with various oral CBD-containing formulations administering a single 2 mg/kg dose in dogs, the median/mean Cmax, Tmax, and half-life were 102.3 ng/mL, 1.5 h, and 4.2 h, respectively (n = 4) (17); 213 ng/mL, 2.1 h, and 2.5 h, respectively (n = 6) (11); 301 ng/mL, 1.4 h, and 1.0 h, respectively, (22); 226 ng/mL, 2.5 h, and 3.8 h, respectively (34).
     • Form comparison · full text, Section 'Pharmacokinetics':CBD administration was also investigated via nasal mucosa (mean dose of 1.7 mg/kg) or intrarectally using suppositories (mean dose of 8.3 mg/kg) compared with oral route (mean dose of 8.3 mg/kg).
     • Form comparison · full text, Section 'Pharmacokinetics':In the present study Cmax was lower compared with CBD plasma/serum concentrations at steady-state following 2–6 weeks oral CBD administration in dogs; 60–125 ng/mL (34), 80–160 ng/mL (23), 5–860 (median 311) ng/mL (20), and 53–201 ng/mL (12).
136. Other animalPharmacokinetics of escalating single-dose administration of cannabidiol to cats.
     J Vet Pharmacol Ther, 2023 · Design: randomized · full text (Europe PMC XML) + abstract · open access (hybrid)
     PMID 36300854DOI 10.1111/jvp.13100PMC10092881 (free full text)
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Tmax · full text, Section 'Pharmacokinetic results':The median Tmax was 2.0–3.0 h in all dosing groups.
     • AUC · full text, Section 'Pharmacokinetic results':The mean AUC0 ‐24 was 8738.1 (4269.6–10690.0) ng/ml × h in the 80 mg/kg dosing group.
     • Food effect · full text, Section 'Administration of CBD and sample collect':The cats were fasted for at least 8 h and monitored overnight by veterinary students.
     • Food effect · full text, Section 'Placebo dose administration':They were fasted for 8 h, and e‐collars were placed the night before administration to mimic a normal dosing round.
137. Other animalTwice-daily oral administration of a cannabidiol and cannabidiolic acid-rich hemp extract was well tolerated in orange-winged Amazon parrots (Amazona amazonica) and has a favorable pharmacokinetic profile.
     Am J Vet Res, 2023 · Design: not stated · abstract only (PubMed) · open access (gold)
     PMID 36795552DOI 10.2460/ajvr.22.11.0197
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:For the multiple-dose study, cannabidiol/cannabidiolic acid mean Cmax was 337.4/602.1 ng/mL with a tmax of 30 minutes and a terminal half-life of 8.6/6.29 hours, respectively.
     • Key findings · abstract:CLINICAL RELEVANCE: Twice daily oral administration of the hemp extract based on 30 mg/kg/32.5 mg/kg of cannabidiol/cannabidiolic acid was well tolerated and maintained plasma concentrations considered to be therapeutic in dogs with osteoarthritis.
     • Cmax · abstract:For the multiple-dose study, cannabidiol/cannabidiolic acid mean Cmax was 337.4/602.1 ng/mL with a tmax of 30 minutes and a terminal half-life of 8.6/6.29 hours, respectively.
     • Tmax · abstract:For the multiple-dose study, cannabidiol/cannabidiolic acid mean Cmax was 337.4/602.1 ng/mL with a tmax of 30 minutes and a terminal half-life of 8.6/6.29 hours, respectively.
     • Food effect · abstract:PROCEDURES: Based on pilot studies, a single-dose study based on 30/32.5 mg/kg of cannabidiol/cannabidiolic acid of a hemp extract was administered orally to 8 fasted parrots, and 10 blood samples were collected over 24 hours after administration.
138. Other animalCannabidiol-Loaded Poly Lactic-Co-Glycolic Acid Nanoparticles with Improved Bioavailability as a Potential for Osteoarthritis Therapeutic.
     Chembiochem, 2023 · Design: not stated · abstract (PubMed); full-text PDF saved · open access (green)
     PMID 36793188DOI 10.1002/cbic.202200698PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Form comparison · full text, p.8:uction, CBD-PLGA-NPs treated cells viability decreased to 67.92% at the concentration of 30 µg/mL, while the viability of the cells was not different compared with the control group at concentrations below. Therefore, 20 µg/mL of CBD-PLGA-NPs were applied for the subsequent experiments. The live/dead cell staining assay revealed that cell survival was obviously decreased with the stimulation of LP
139. Other animalEnhanced Intramuscular Bioavailability of Cannabidiol Using Nanocrystals: Formulation, In Vitro Appraisal, and Pharmacokinetics.
     AAPS PharmSciTech, 2022 · Design: not stated · abstract only (PubMed) · closed/paywalled
     PMID 35288801DOI 10.1208/s12249-022-02239-3
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:CBD-NC freeze-dried powder using bovine serum albumin (BSA) as cryoprotectant had good redispersibility, and the average particle size was 139.1±1.4 nm after reconstitution.
     • Key findings · abstract:The in vivo results showed that AUC0-24 h and Cmax of CBD by IM injection of CBD nanocrystals increased significantly compared with that of oral (P.O) administration of CBD nanocrystals and CBD oil solution.
     • Cmax · abstract:The in vivo results showed that AUC0-24 h and Cmax of CBD by IM injection of CBD nanocrystals increased significantly compared with that of oral (P.O) administration of CBD nanocrystals and CBD oil solution.
     • AUC · abstract:The in vivo results showed that AUC0-24 h and Cmax of CBD by IM injection of CBD nanocrystals increased significantly compared with that of oral (P.O) administration of CBD nanocrystals and CBD oil solution.
140. Other animalPharmacokinetics of cannabidiol following single oral and oral transmucosal administration in dogs.
     Front Vet Sci, 2022 · Design: not stated · n: 6 dogs · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 36686155DOI 10.3389/fvets.2022.1104152PMC9859632 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:RESULTS: CBD Cmax, Tmax, terminal half-life and AUC0 - t were 206.77 ± 167 and 200.33 ± 158.33 ng/mL, 2.17 ± 0.98 and 1.92 ± 1.11 h, 2.67 ± 0.53 and 2.62 ± 0.64 h, 647.51 ± 453.17, and 536.05 ± 370.21 h*ng/mL, following oral and OTM administration, respectively.
     • Cmax · abstract:RESULTS: CBD Cmax, Tmax, terminal half-life and AUC0 - t were 206.77 ± 167 and 200.33 ± 158.33 ng/mL, 2.17 ± 0.98 and 1.92 ± 1.11 h, 2.67 ± 0.53 and 2.62 ± 0.64 h, 647.51 ± 453.17, and 536.05 ± 370.21 h*ng/mL, following oral and OTM administration, respectively.
     • Tmax · abstract:RESULTS: CBD Cmax, Tmax, terminal half-life and AUC0 - t were 206.77 ± 167 and 200.33 ± 158.33 ng/mL, 2.17 ± 0.98 and 1.92 ± 1.11 h, 2.67 ± 0.53 and 2.62 ± 0.64 h, 647.51 ± 453.17, and 536.05 ± 370.21 h*ng/mL, following oral and OTM administration, respectively.
     • AUC · abstract:RESULTS: CBD Cmax, Tmax, terminal half-life and AUC0 - t were 206.77 ± 167 and 200.33 ± 158.33 ng/mL, 2.17 ± 0.98 and 1.92 ± 1.11 h, 2.67 ± 0.53 and 2.62 ± 0.64 h, 647.51 ± 453.17, and 536.05 ± 370.21 h*ng/mL, following oral and OTM administration, respectively.
     • Cmax · full text, Table 2:n pharmacokinetic parameters obtained following oral and OTM administration of CBD at 1 mg/kg in dogs (6 dogs/group). Parameter λz t1/2 Tmax Cmax AUC0-t AUC0−∞ AUCEstr AUMC0−∞ MRT Unit 1/h h h ng/mL h*ng/mL h*ng/mL % h2*ng/mL h Oral Dog 1 0.33 2.09 2 135.60 394.33 410.57 4.12 1371.46 3.34 Dog 2 0.21 3.27 2 192.00 482.00 524.49 8.81 2177.71 4.15 Dog 3 0.22
     • Cmax · full text, Section 'Results':The CBD plasma peak (Cmax) was achieved between 1 and 4 h (Tmax) in both treatment groups and ranged between 73 and 526 and 67 and 451 ng/mL following oral and OTM administration, respectively.
     • Cmax · full text, Section 'Results':Following non-compartmental analysis, the extrapolated percentage of the area under the curve (AUC) of one dog in the oral group was >20% (26.8%), therefore the pharmacokinetic parameters depending on terminal rate constant of this subject were considered unreliable and excluded, while parameters such as Cmax, Tmax and AUC0 − t were maintained.
     • Tmax · full text, Table 2:Main pharmacokinetic parameters obtained following oral and OTM administration of CBD at 1 mg/kg in dogs (6 dogs/group). Parameter λz t1/2 Tmax Cmax AUC0-t AUC0−∞ AUCEstr AUMC0−∞ MRT Unit 1/h h h ng/mL h*ng/mL h*ng/mL % h2*ng/mL h Oral Dog 1 0.33 2.09 2 135.60 394.33 410.57 4.12 1371.46 3.34 Dog 2 0.21 3.27 2 192.00 482.00 524.49 8.81 2177.71 4.15 Dog 3 0.
     • Tmax · full text, Section 'Results':The CBD plasma peak (Cmax) was achieved between 1 and 4 h (Tmax) in both treatment groups and ranged between 73 and 526 and 67 and 451 ng/mL following oral and OTM administration, respectively.
     • Tmax · full text, Section 'Results':Following non-compartmental analysis, the extrapolated percentage of the area under the curve (AUC) of one dog in the oral group was >20% (26.8%), therefore the pharmacokinetic parameters depending on terminal rate constant of this subject were considered unreliable and excluded, while parameters such as Cmax, Tmax and AUC0 − t were maintained.
     • AUC · full text, Table 2:acokinetic parameters obtained following oral and OTM administration of CBD at 1 mg/kg in dogs (6 dogs/group). Parameter λz t1/2 Tmax Cmax AUC0-t AUC0−∞ AUCEstr AUMC0−∞ MRT Unit 1/h h h ng/mL h*ng/mL h*ng/mL % h2*ng/mL h Oral Dog 1 0.33 2.09 2 135.60 394.33 410.57 4.12 1371.46 3.34 Dog 2 0.21 3.27 2 192.00 482.00 524.49 8.81 2177.71 4.15 Dog 3 0.22 3.17 2
     • AUC · full text, Section 'Results':Following non-compartmental analysis, the extrapolated percentage of the area under the curve (AUC) of one dog in the oral group was >20% (26.8%), therefore the pharmacokinetic parameters depending on terminal rate constant of this subject were considered unreliable and excluded, while parameters such as Cmax, Tmax and AUC0 − t were maintained.
141. Other animalFeeding decreases the oral bioavailability of cannabidiol and cannabidiolic acid in hemp oil in New Zealand White rabbits (Oryctolagus cuniculus).
     Am J Vet Res, 2022 · Design: not stated · abstract only (PubMed) · open access (gold)
     PMID 35947680DOI 10.2460/ajvr.22.01.0006
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:RESULTS: For CBD, the area under the curve extrapolated to infinity (AUC)0-∞ was 179.8 and 102 hours X ng/mL, the maximum plasma concentration (Cmax) was 30.4 and 15 ng/mL, the time to Cmax (tmax) was 3.78 and 3.25 hours, and the terminal half-life (t1/2λ) was 7.12 and 3.8 hours in phase 1 and phase 2, respectively.
     • Key findings · abstract:For CBDA, the AUC0-∞ was 12,286 and 6,176 hours X ng/mL, Cmax was 2,573 and 1,196 ng/mL, tmax was 1.07 and 1.12 hours, and t1/2λ was 3.26 and 3.49 hours in phase 1 and phase 2, respectively.
     • Key findings · abstract:CLINICAL RELEVANCE: CBD and CBDA reached a greater Cmax and had a longer t1/2λ in phase[excerpt truncated in our database — see source]
     • Cmax · abstract:RESULTS: For CBD, the area under the curve extrapolated to infinity (AUC)0-∞ was 179.8 and 102 hours X ng/mL, the maximum plasma concentration (Cmax) was 30.4 and 15 ng/mL, the time to Cmax (tmax) was 3.78 and 3.25 hours, and the terminal half-life (t1/2λ) was 7.12 and 3.8 hours in phase 1 and phase 2, respectively.
     • Cmax · abstract:For CBDA, the AUC0-∞ was 12,286 and 6,176 hours X ng/mL, Cmax was 2,573 and 1,196 ng/mL, tmax was 1.07 and 1.12 hours, and t1/2λ was 3.26 and 3.49 hours in phase 1 and phase 2, respectively.
     • Cmax · abstract:CLINICAL RELEVANCE: CBD and CBDA reached a greater Cmax and had a longer t1/2λ in phase
     • Tmax · abstract:RESULTS: For CBD, the area under the curve extrapolated to infinity (AUC)0-∞ was 179.8 and 102 hours X ng/mL, the maximum plasma concentration (Cmax) was 30.4 and 15 ng/mL, the time to Cmax (tmax) was 3.78 and 3.25 hours, and the terminal half-life (t1/2λ) was 7.12 and 3.8 hours in phase 1 and phase 2, respectively.
     • Tmax · abstract:For CBDA, the AUC0-∞ was 12,286 and 6,176 hours X ng/mL, Cmax was 2,573 and 1,196 ng/mL, tmax was 1.07 and 1.12 hours, and t1/2λ was 3.26 and 3.49 hours in phase 1 and phase 2, respectively.
     • AUC · abstract:RESULTS: For CBD, the area under the curve extrapolated to infinity (AUC)0-∞ was 179.8 and 102 hours X ng/mL, the maximum plasma concentration (Cmax) was 30.4 and 15 ng/mL, the time to Cmax (tmax) was 3.78 and 3.25 hours, and the terminal half-life (t1/2λ) was 7.12 and 3.8 hours in phase 1 and phase 2, respectively.
     • AUC · abstract:For CBDA, the AUC0-∞ was 12,286 and 6,176 hours X ng/mL, Cmax was 2,573 and 1,196 ng/mL, tmax was 1.07 and 1.12 hours, and t1/2λ was 3.26 and 3.49 hours in phase 1 and phase 2, respectively.
     • Food effect · abstract:CLINICAL RELEVANCE: CBD and CBDA reached a greater Cmax and had a longer t1/2λ in phase 1 (without food) compared with phase 2 (with food).
142. Other animalPharmacokinetics of Cannabidiol Following Intranasal, Intrarectal, and Oral Administration in Healthy Dogs.
     Front Vet Sci, 2022 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 35754531DOI 10.3389/fvets.2022.899940PMC9215213 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:The mean area under the curve (AUC) after IN and PO CBD administration was 61 and 1,376 ng/mL*h, respectively.
     • Key findings · abstract:The maximal plasma CBD concentration (Cmax) after IN and PO CBD administration was 28 and 217 ng/mL reached after 0.5 and 3.5 h (Tmax), respectively.
     • Key findings · abstract:Higher AUC and Cmax were achieved with 100 mg PO compared to 20 mg IN, but no significant differences were found when AUC (p = 0.09) and Cmax (p = 0.44) were normalized to 1 mg dosages.
     • Cmax · abstract:The maximal plasma CBD concentration (Cmax) after IN and PO CBD administration was 28 and 217 ng/mL reached after 0.5 and 3.5 h (Tmax), respectively.
     • Cmax · abstract:Higher AUC and Cmax were achieved with 100 mg PO compared to 20 mg IN, but no significant differences were found when AUC (p = 0.09) and Cmax (p = 0.44) were normalized to 1 mg dosages.
     • Tmax · abstract:The maximal plasma CBD concentration (Cmax) after IN and PO CBD administration was 28 and 217 ng/mL reached after 0.5 and 3.5 h (Tmax), respectively.
     • Tmax · abstract:Significant differences between IN and PO administration were found in the Tmax (p = 0.04).
     • AUC · abstract:The mean area under the curve (AUC) after IN and PO CBD administration was 61 and 1,376 ng/mL*h, respectively.
     • AUC · abstract:Higher AUC and Cmax were achieved with 100 mg PO compared to 20 mg IN, but no significant differences were found when AUC (p = 0.09) and Cmax (p = 0.44) were normalized to 1 mg dosages.
     • Cmax · full text, Table 1:e of CBD intranasally (20 mg) (IN) and orally (100 mg) (PO). Pharmacokinetic parameter IN PO AUC(0−∞) (ng/mL*h)* 61.31 ± 88.22 1376.03 ± 828.95 Cmax (ng/mL)* 27.96 ± 25.29 216.76 ± 108.51 AUC(0−∞) (ng/mL*h)** 3.06 ± 4.41 13.76 ± 8.28 Cmax (ng/mL)** 1.39 ± 1.26 2.16 ± 1.08 Tmax (h)† 0.49 ± 0.29 3.50 ± 0.55 T1/2el (h) 7.02 ± 7.97 15.65 ± 2.82 kel (1/h) 0.52 ± 0.54 0.045 ± 0.007 MRT (h) 10.30 ±
     • Cmax · full text, Section 'Results':The maximal plasma CBD concentration (Cmax) after IN and PO CBD administration before dose normalization was 27.96 and 216.76 ng/ml and 1.39 and 2.16 ng/mL after dose normalization, reached at 0.5 and 3.5 h (Tmax), respectively.
     • Tmax · full text, Table 1:.22 1376.03 ± 828.95 Cmax (ng/mL)* 27.96 ± 25.29 216.76 ± 108.51 AUC(0−∞) (ng/mL*h)** 3.06 ± 4.41 13.76 ± 8.28 Cmax (ng/mL)** 1.39 ± 1.26 2.16 ± 1.08 Tmax (h)† 0.49 ± 0.29 3.50 ± 0.55 T1/2el (h) 7.02 ± 7.97 15.65 ± 2.82 kel (1/h) 0.52 ± 0.54 0.045 ± 0.007 MRT (h) 10.30 ± 14.04 13.07 ± 3.61 Relative F (%) 22.28% /
     • Tmax · full text, Section 'Results':The maximal plasma CBD concentration (Cmax) after IN and PO CBD administration before dose normalization was 27.96 and 216.76 ng/ml and 1.39 and 2.16 ng/mL after dose normalization, reached at 0.5 and 3.5 h (Tmax), respectively.
     • AUC · full text, Table 1:an ± SD) of CBD in 6 dogs administered a single dose of CBD intranasally (20 mg) (IN) and orally (100 mg) (PO). Pharmacokinetic parameter IN PO AUC(0−∞) (ng/mL*h)* 61.31 ± 88.22 1376.03 ± 828.95 Cmax (ng/mL)* 27.96 ± 25.29 216.76 ± 108.51 AUC(0−∞) (ng/mL*h)** 3.06 ± 4.41 13.76 ± 8.28 Cmax (ng/mL)** 1.39 ± 1.26 2.16 ± 1.08 Tmax (h)† 0.49 ± 0.29 3.50 ± 0.55 T1/2el (h) 7.02 ± 7.97 15.65 ± 2.82
     • AUC · full text, Section 'Results':The mean AUC0−inf after IN and PO CBD administration before dose normalization was 61.31 and 1376.03 ng/mL*h and after normalization to 1 mg dosages was 3.06 and 13.76 ng/mL*h, respectively.
143. Other animalDevelopment and pharmacokinetic evaluation of a self-nanoemulsifying drug delivery system for the oral delivery of cannabidiol.
     Eur J Pharm Sci, 2022 · Design: not stated · abstract only (PubMed) · open access (hybrid)
     PMID 34763088DOI 10.1016/j.ejps.2021.106058
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:Compared to MCT-CBD, administration of the SNEDDS formulations led to more rapid absorption of CBD (median Tmax values: 0.5 h (F2), 1 h (F4), 6 h (MCT-CBD)).
     • Key findings · abstract:Administration of F2 and F4 formulations also improved the systemic exposure to CBD by 2.2 and 2.8-fold compared to MCT-CBD; however, no improvement was found compared to SO-CBD.
     • Tmax · abstract:Compared to MCT-CBD, administration of the SNEDDS formulations led to more rapid absorption of CBD (median Tmax values: 0.5 h (F2), 1 h (F4), 6 h (MCT-CBD)).
     • Relative bioavailability · abstract:Administration of F2 and F4 formulations also improved the systemic exposure to CBD by 2.2 and 2.8-fold compared to MCT-CBD; however, no improvement was found compared to SO-CBD.
144. Other animalPharmacokinetics of cannabidiol in a randomized crossover trial in senior horses.
     Am J Vet Res, 2022 · Design: randomized; crossover · abstract only (PubMed) · open access (gold)
     PMID 35895770DOI 10.2460/ajvr.22.02.0028
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:RESULTS: Concentrations of CBD and metabolites (7-COH CBD and 7-COOH CBD) were detected in all plasma samples up to 8 hours after dosing (oral and IV), with 7-COOH CBD being the most predominant metabolite.
     • Key findings · abstract:Oral bioavailability for CBD was 7.92%.
145. Other animalPharmacokinetics, Safety, and Synovial Fluid Concentrations of Single- and Multiple-Dose Oral Administration of 1 and 3 mg/kg Cannabidiol in Horses.
     J Equine Vet Sci, 2022 · Design: randomized · n: 12 horses · abstract only (PubMed) · closed/paywalled
     PMID 35307550DOI 10.1016/j.jevs.2022.103933
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:Mean ± SD Cmax and tmax were 4.3 ± 2.1 ng/ml and 4.1 ± 4.1 hours, and 19.9 ± 15.6 ng/ml and 5.0 ± 3.7 hours for Groups 1 and 2, respectively.
     • Key findings · abstract:CBD had dose-dependent, but variable, oral bioavailability at 1 mg/kg and 3 mg/kg daily dosing and was consistently detectable at steady state in synovial fluid at the higher dose.
     • Cmax · abstract:Mean ± SD Cmax and tmax were 4.3 ± 2.1 ng/ml and 4.1 ± 4.1 hours, and 19.9 ± 15.6 ng/ml and 5.0 ± 3.7 hours for Groups 1 and 2, respectively.
     • Tmax · abstract:Mean ± SD Cmax and tmax were 4.3 ± 2.1 ng/ml and 4.1 ± 4.1 hours, and 19.9 ± 15.6 ng/ml and 5.0 ± 3.7 hours for Groups 1 and 2, respectively.
146. Other animalPharmacokinetic Evaluation of a Cannabidiol Supplement in Horses.
     J Equine Vet Sci, 2022 · Design: randomized; crossover · abstract only (PubMed) · closed/paywalled
     PMID 34923070DOI 10.1016/j.jevs.2021.103842
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:Plasma CBD and delta-9-tetrahydrocannabinol (THC) were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) daily through day 10, then on day 14 after beginning CBD administration.
     • Key findings · abstract:After administration of 0.35 mg/kg of CBD, the Cmax of CBD was 6.6 ± 2.1 ng/mL while Tmax was 1.8 ± 1.2 hour, whereas the Cmax for THC was 0.7 ± 0.6 ng/mL with a Tmax of 2.5 ± 1 hour.
     • Key findings · abstract:After administration of 2.0 mg/kg of CBD, the Cmax of CBD was 51 ± 14 ng/mL with a mean Tmax of 2.4 ± 1.1 hour and terminal phase half-life of 10.4 ± 6 hour, whereas the Cmax of THC was 7.5 ± 2.2 ng/mL with a[excerpt truncated in our database — see source]
     • Cmax · abstract:After administration of 0.35 mg/kg of CBD, the Cmax of CBD was 6.6 ± 2.1 ng/mL while Tmax was 1.8 ± 1.2 hour, whereas the Cmax for THC was 0.7 ± 0.6 ng/mL with a Tmax of 2.5 ± 1 hour.
     • Cmax · abstract:After administration of 2.0 mg/kg of CBD, the Cmax of CBD was 51 ± 14 ng/mL with a mean Tmax of 2.4 ± 1.1 hour and terminal phase half-life of 10.4 ± 6 hour, whereas the Cmax of THC was 7.5 ± 2.2 ng/mL with a Tmax of 2.9 ± 1.1 hour.
     • Tmax · abstract:After administration of 0.35 mg/kg of CBD, the Cmax of CBD was 6.6 ± 2.1 ng/mL while Tmax was 1.8 ± 1.2 hour, whereas the Cmax for THC was 0.7 ± 0.6 ng/mL with a Tmax of 2.5 ± 1 hour.
     • Tmax · abstract:After administration of 2.0 mg/kg of CBD, the Cmax of CBD was 51 ± 14 ng/mL with a mean Tmax of 2.4 ± 1.1 hour and terminal phase half-life of 10.4 ± 6 hour, whereas the Cmax of THC was 7.5 ± 2.2 ng/mL with a Tmax of 2.9 ± 1.1 hour.
147. Other animalSerum Cannabinoid 24 h and 1 Week Steady State Pharmacokinetic Assessment in Cats Using a CBD/CBDA Rich Hemp Paste.
     Front Vet Sci, 2022 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 35937287DOI 10.3389/fvets.2022.895368PMC9355628 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:Using a standard dose of paste (6.4 mg/CBD + CBDA 5.3 mg/gram) across 8 cats weighing between 4.2 and 5.4 kg showed an average maximal concentration of CBD at 282.0 ± 149.4 ng/mL with a half-life of ~2.1 ± 1.1 h, and CBDA concentrations of 1,011.3 ± 495.4 ng/mL with a half-life of ~2.7 ± 1.4 h, showing superior absorption of CBDA.
     • Key findings · abstract:After twice daily dosing for 1 week the serum concentrations 6 h after a morning dosing showed that the acidic forms of the cannabinoids were approximately double the concentration of the non-acidic forms like CBD and Δ9- tetrahydrocannabinol (THC).
     • Key findings · abstract:In addition,[excerpt truncated in our database — see source]
     • Food effect · full text, Section 'Animals and Animal Health':The cats were fasted prior to administration for nearly 15 h, and all cats were observed to accept and eat the paste without any negative behaviors and were fed their normal daily meal ~1 h after oral paste consumption.
     • Form comparison · full text, Section 'Results':One week 6 h post morning dosing concentrations were measured and compared to mean calculations.
148. Other animalVegetable oils composition affects the intestinal lymphatic transport and systemic bioavailability of co-administered lipophilic drug cannabidiol.
     Int J Pharm, 2022 · Design: not stated · abstract only (PubMed) · not checked (off-topic)
     PMID 35753538DOI 10.1016/j.ijpharm.2022.121947
     Verification: abstract-only auto-extract; unverified
149. Other animalPlasma Pharmacokinetics of Cannabidiol Following Oral Administration of Cannabidiol Oil to Dairy Calves.
     Front Vet Sci, 2022 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 35141311DOI 10.3389/fvets.2022.789495PMC8818876 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Cmax · full text, Table 1:0.62–48.64 AUClast h*ug/mL 1.09 1.53 0.19 0.83 0.73 0.65 0.69 0.70 0.73 0.19–1.53 Cl_F L/kg/h 3.86 2.92 20.77 4.85 5.5 3.99 4.68 5.29 4.68 2.92–20.77 Cmax ug/mL 0.09 0.09 0.01 0.08 0.03 0.04 0.04 0.05 0.04 0.01–0.09 Tmax h 6 18 8 2 12 8 8 7.5 8 2.0–18.0 Lambda_z (h−1) 0.04 0.05 0.03 0.03 0.04 0.02 0.02 0.03 0.03 0.02–0.05 HL_Lambda_z h 17.33 13.83 20.92 24.08 19.17 47.14 31.43 23.02 20.92 13.83–47
     • Cmax · full text, Section 'Results':Geometric mean Cmax plasma concentration of CBD was 0.05 ug/mL (range −0.01–0.09 ug/mL), which was reached 7.5 h (range −2–18 h) after oral administration.
     • Tmax · full text, Table 1:0.73 0.19–1.53 Cl_F L/kg/h 3.86 2.92 20.77 4.85 5.5 3.99 4.68 5.29 4.68 2.92–20.77 Cmax ug/mL 0.09 0.09 0.01 0.08 0.03 0.04 0.04 0.05 0.04 0.01–0.09 Tmax h 6 18 8 2 12 8 8 7.5 8 2.0–18.0 Lambda_z (h−1) 0.04 0.05 0.03 0.03 0.04 0.02 0.02 0.03 0.03 0.02–0.05 HL_Lambda_z h 17.33 13.83 20.92 24.08 19.17 47.14 31.43 23.02 20.92 13.83–47.14 MRTINF h 25.46 25.25 35.30 28.54 31.18 67.55 47.20 35.00 31.18
     • AUC · full text, Table 1:dministration at 5 mg/kg. Calf ID Parameter Unit 6,495 6,521 6,523 6,551 6,553 6,586 6,589 Geometric mean Median Range AUC0−∞ h*ug/mL 1.30 1.71 0.24 1.04 0.92 1.26 1.07 0.95 1.07 0.24–1.71 AUC_%Extrap % 16.32 10.62 23.63 19.75 20.48 48.64 35.54 22.44 20.48 10.62–48.64 AUClast h*ug/mL 1.09 1.53 0.19 0.83 0.73 0.65 0.69 0.70 0.73 0.19–1.53 Cl_F L/kg/h 3.86 2.92 20.77 4
     • AUC · full text, Section 'Results':Area under the curve to the last time point (AUClast) geometric mean was 0.7 h*ug/mL (range −0.19–1.53 h*ug/mL) and the AUC0−∞ being 0.95 h*ug/mL with the extrapolated portion following the last time point representing 22.44% (range −10.62–48.64) of the value.
     • Food effect · full text, Section 'Animals':Calves were fed 3 quarts of milk replacer twice daily at 7:00 and 17:00 h.
150. Other animalCannabidiol (CBD) Dosing: Plasma Pharmacokinetics and Effects on Accumulation in Skeletal Muscle, Liver and Adipose Tissue.
     Nutrients, 2022 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 35631242DOI 10.3390/nu14102101PMC9146469 (free full text)
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:The rise in tissue CBD was closely related to specific pharmacokinetic parameters, and adipose tissue levels were ~10 to ~100 fold greater than liver or muscle.
     • Relative bioavailability · abstract:The rise in tissue CBD was closely related to specific pharmacokinetic parameters, and adipose tissue levels were ~10 to ~100 fold greater than liver or muscle.
     • Food effect · abstract:CBD was fed relative to body mass at 0 (control), 30, 115, or 230 mg/Kg/day for 28 days; with 6 males and 6 females per dosing group.
     • AUC · full text, Section '2.3. Plasma Pharmacokinetics':(iii) area under the curve up to 24 h (AUC0-24);
     • Food effect · full text, Section '2.1. Animals':Animals were fasted for 15 h prior to pharmacokinetic investigations.
     • Food effect · full text, Section '2.2. CBD Characterisation and Administra':Each group was fed CBD relative to body mass at doses of 0 mg/kg/day as a control comprised solely of the CBD carrier, 30 mg/kg/day (“low dose”); 115 mg/kg/day (“medium dose”) and 230 mg/kg/day (“high dose”).
     • Food effect · full text, Section '2.3. Plasma Pharmacokinetics':In animals fed the 115 mg/kg/day CBD dose, pharmacokinetics were assessed both on Day 1 and Day 28.
151. Other animalLipid-based formulations to increase cannabidiol bioavailability: In vitro digestion tests, pre-clinical assessment and clinical trial.
     Int J Pharm, 2021 · Design: crossover · n: 11 volunteers · abstract only (PubMed) · closed/paywalled
     PMID 34624443DOI 10.1016/j.ijpharm.2021.121159
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:In vivo tests (mouse) revealed that SEDDS promoted the highest CBD exposure, exhibiting an area under the plasma concentration-time curve (AUC0-6h) 1.48 times greater than GML and 3.97 times greater than that of the MCT formulation.
     • Key findings · abstract:A single-dose, open-label, crossover study performed in 11 volunteers showed that SEDDS increased CBD AUC0-12h by 1.12 and 1.48 times in relation to GML and MCT, respectively.
     • Key findings · abstract:The AUC correlation between mice and humans was 0.98.
     • AUC · abstract:In vivo tests (mouse) revealed that SEDDS promoted the highest CBD exposure, exhibiting an area under the plasma concentration-time curve (AUC0-6h) 1.48 times greater than GML and 3.97 times greater than that of the MCT formulation.
     • AUC · abstract:A single-dose, open-label, crossover study performed in 11 volunteers showed that SEDDS increased CBD AUC0-12h by 1.12 and 1.48 times in relation to GML and MCT, respectively.
     • AUC · abstract:The AUC correlation between mice and humans was 0.98.
152. Other animalSodium alginate microencapsulation improves the short-term oral bioavailability of cannabidiol when administered with deoxycholic acid.
     PLoS One, 2021 · Design: not stated · n: 4 mice · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 34138862DOI 10.1371/journal.pone.0243858PMC8211198 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:To assess the short-term bioavailability of CBD, plasma and brain samples were collected at 0.3, 1 and 3 hours post administration and CBD levels were analysed with liquid chromatography mass spectrometer.
     • Key findings · abstract:Mice that received CBD capsules + DCA capsules showed a 40% and 47% increase in CBD plasma concentration compared to mice on CBD capsules and naked CBD oil, respectively.
     • Cmax · full text, Table 1:ain Capsule Capsule + DCA Naked Capsule Capsule + DCA Naked Parameter Unit t1/2 h 1.1 0.4 2.2 0.9 4.5 Not determined tmax h 0.3 1.0 0.3 1.0 0.7 2.0 Cmax ng/mL or ng/g 10.9 11.0 7.7 280.9 1048.2 421.5 AUC 0-t ng/mL*h 15.2 16.7 12.9 368.1 1242.1 447.4 AUC 0-inf_obs ng/mL*h 16.3 6.5 14.9 75.0 4378.4 Not determined
     • Cmax · full text, Section 'Pharmacokinetics of capsulated CBD':The current results demonstrate that plasma bioavailability as indicated by Cmax and AUC0-t was mildly increased for encapsulated CBD compared to naked oil (by 27.3% and 14.6%, respectively).
     • Tmax · full text, Table 1:n plasma and brain. Plasma Brain Capsule Capsule + DCA Naked Capsule Capsule + DCA Naked Parameter Unit t1/2 h 1.1 0.4 2.2 0.9 4.5 Not determined tmax h 0.3 1.0 0.3 1.0 0.7 2.0 Cmax ng/mL or ng/g 10.9 11.0 7.7 280.9 1048.2 421.5 AUC 0-t ng/mL*h 15.2 16.7 12.9 368.1 1242.1 447.4 AUC 0-inf_obs ng/mL*h 16.3 6.5 14.9 75.0 4378.4 Not determined
     • Tmax · full text, Section 'Pharmacokinetics of capsulated CBD':Consistent with the latter, CBD analyses in brain tissue revealed in mice that were given CBD capsules, the tmax was 1 h, half of naked CBD group mice, indicating markedly faster brain tissue uptake of CBD by the MVSA capsulation.
     • AUC · full text, Table 1:DCA Naked Parameter Unit t1/2 h 1.1 0.4 2.2 0.9 4.5 Not determined tmax h 0.3 1.0 0.3 1.0 0.7 2.0 Cmax ng/mL or ng/g 10.9 11.0 7.7 280.9 1048.2 421.5 AUC 0-t ng/mL*h 15.2 16.7 12.9 368.1 1242.1 447.4 AUC 0-inf_obs ng/mL*h 16.3 6.5 14.9 75.0 4378.4 Not determined
     • AUC · full text, Section 'Pharmacokinetics of capsulated CBD':The current results demonstrate that plasma bioavailability as indicated by Cmax and AUC0-t was mildly increased for encapsulated CBD compared to naked oil (by 27.3% and 14.6%, respectively).
     • Relative bioavailability · full text, Section 'Pharmacokinetics of capsulated CBD':When CBD capsules were given in combination with DCA capsules (CBD capsule + DCA capsule group), the mean brain concentration of CBD was 1048 ng/mg tissue, a remarkable 40- and 30-fold increase compared to the naked CBD oil and CBD capsule groups, respectively.
     • Form comparison · full text, Section 'CBD and DCA formulations':Solutions containing 1.5% MVSA in 80 mL of HPLC-grade deionised water were mixed overnight.
     • Form comparison · full text, Section 'CBD and DCA formulations':The CBD formulation was made by adding 800 μL of Miglyol 812N containing 109.24 mg CBD to the MVSA solution while protected from air and light and mixed for 3 days.
     • Form comparison · full text, Section 'CBD and DCA formulations':The DCA formulation was made by adding 10 mg of DCA to a separate MVSA solution and mixed overnight.
153. Other animalNatural sesame oil is superior to pre-digested lipid formulations and purified triglycerides in promoting the intestinal lymphatic transport and systemic bioavailability of cannabidiol.
     Eur J Pharm Biopharm, 2021 · Design: not stated · abstract only (PubMed) · open access (green)
     PMID 33677067DOI 10.1016/j.ejpb.2021.02.013
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:The aim of this study was to test the hypothesis that pre-digested lipid formulations (oleic acid, linoleic acid, oleic acid with 2-oleoylglycerol, oleic acid with 2-oleoylglycerol and oleic acid with glycerol) could reduce variability and increase the extent of the intestinal lymphatic transport and oral bioavailability of CBD.
154. Other animalPharmacokinetics and effects on arachidonic acid metabolism of low doses of cannabidiol following oral administration to horses.
     Drug Test Anal, 2021 · Design: randomized; crossover · abstract only (PubMed) · closed/paywalled
     PMID 33723919DOI 10.1002/dta.3028
     Verification: abstract-only auto-extract; unverified
155. Other animalRandomized, placebo-controlled, 28-day safety and pharmacokinetics evaluation of repeated oral cannabidiol administration in healthy dogs.
     Am J Vet Res, 2021 · Design: randomized · n: n = 4 · abstract only (PubMed) · closed/paywalled
     PMID 33904801DOI 10.2460/ajvr.82.5.405
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:Relative to placebo administration, CBD administration at 12 mg/kg/d resulted in more gastrointestinal adverse events (mainly hypersalivation) and significantly higher serum alkaline phosphatase activity.
     • Key findings · abstract:Within each CBD dose group, repeated administration increased total systemic exposure to CBD 1.6- to 3.3-fold.
     • Key findings · abstract:The 24-hour trough plasma CBD concentrations were also dose dependent, with a steady state reached following 2 weeks of administration.
     • Key findings · abstract:CONCLUSIONS AND CLINICAL RELEVANCE: Repeated, daily oral administration of the CBD formulation led to dose-dependent increases in total system[excerpt truncated in our database — see source]
     • Relative bioavailability · abstract:Within each CBD dose group, repeated administration increased total systemic exposure to CBD 1.6- to 3.3-fold.
156. Other animalThe effect of piperine on oral absorption of cannabidiol following acute vs. chronic administration.
     Eur J Pharm Sci, 2020 · Design: not stated · abstract only (PubMed) · closed/paywalled
     PMID 32198013DOI 10.1016/j.ejps.2020.105313
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:Both groups resulted in approximate 2.5-fold increase in oral bioavailability of CBD compared to control group without piperine.
     • Relative bioavailability · abstract:Both groups resulted in approximate 2.5-fold increase in oral bioavailability of CBD compared to control group without piperine.
157. Other animalPharmacokinetic and Safety Evaluation of Various Oral Doses of a Novel 1:20 THC:CBD Cannabis Herbal Extract in Dogs.
     Front Vet Sci, 2020 · Design: randomized · n: n = 6 · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 33134364DOI 10.3389/fvets.2020.583404PMC7550466 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:Results: Cannabinoids CBD, THC, CBC, and metabolites 6-OH-CBD, 7-OH-CBD, 11-OH-THC, and THC-COOH were quantified in plasma.
     • Key findings · abstract:CBD and THC were rapidly absorbed (mean T max of 1.9-2.3 h) and initially depleted rapidly (mean CBD T 1/2β of 2.3-2.6 h).
     • Tmax · abstract:CBD and THC were rapidly absorbed (mean T max of 1.9-2.3 h) and initially depleted rapidly (mean CBD T 1/2β of 2.3-2.6 h).
     • Fractional absorption · abstract:CBD and THC were rapidly absorbed (mean T max of 1.9-2.3 h) and initially depleted rapidly (mean CBD T 1/2β of 2.3-2.6 h).
     • Cmax · full text, Table 3:6/dosing group; mixed gender) receiving a single oral dose of 1:20 THC:CBD CHE formulation at different dose sizes. Cannabinoid Dose (mg/kg) Tmax (h) Cmax (ng/mL) Dose-Adjusted Cmax (ng/mL per mg/kg)1 T1/2β (h)2 AUC0–12h (ng * h/mL) Dose-Adjusted AUC0–12h (ng * h/mL per mg/kg)1 T1/2λ (h)3 AUClast (ng * h/mL) “Steady-state” conc. (ng/mL)4 CBD 2 2.1 (1.0) 213 (49) 107A (24) 2.5 (0.5) 692 (292) 346A
     • Tmax · full text, Table 3:ogs (n = 6/dosing group; mixed gender) receiving a single oral dose of 1:20 THC:CBD CHE formulation at different dose sizes. Cannabinoid Dose (mg/kg) Tmax (h) Cmax (ng/mL) Dose-Adjusted Cmax (ng/mL per mg/kg)1 T1/2β (h)2 AUC0–12h (ng * h/mL) Dose-Adjusted AUC0–12h (ng * h/mL per mg/kg)1 T1/2λ (h)3 AUClast (ng * h/mL) “Steady-state” conc. (ng/mL)4 CBD 2 2.1 (1.0) 213 (49) 107A (24) 2.5 (0.5) 692 (2
     • AUC · full text, Table 3:1:20 THC:CBD CHE formulation at different dose sizes. Cannabinoid Dose (mg/kg) Tmax (h) Cmax (ng/mL) Dose-Adjusted Cmax (ng/mL per mg/kg)1 T1/2β (h)2 AUC0–12h (ng * h/mL) Dose-Adjusted AUC0–12h (ng * h/mL per mg/kg)1 T1/2λ (h)3 AUClast (ng * h/mL) “Steady-state” conc. (ng/mL)4 CBD 2 2.1 (1.0) 213 (49) 107A (24) 2.5 (0.5) 692 (292) 346A (146) 13.3 (4.1) 759 (335) NA 5 1.9 (0.6) 838 (304) 168A (61)
     • AUC · full text, Section 'PK Results':Dose adjusted AUC0−12h (i.e., AUC0−12h/dose) showed a statistically significant increase with increasing doses for THC (ANOVA p = 0.026).
     • Food effect · full text, Table 3:Mean (SD) cannabinoid PK parameters in fasted beagle cross dogs (n = 6/dosing group; mixed gender) receiving a single oral dose of 1:20 THC:CBD CHE formulation at different dose sizes. Cannabinoid Dose (mg/kg) Tmax (h) Cmax (ng/mL) Dose-Adjusted Cmax (ng/mL per mg/kg)1 T1/2β (h)2 AUC0–12h (ng *
158. Other animalPharmacokinetics of Cannabidiol, Cannabidiolic Acid, Δ9-Tetrahydrocannabinol, Tetrahydrocannabinolic Acid and Related Metabolites in Canine Serum After Dosing With Three Oral Forms of Hemp Extract.
     Front Vet Sci, 2020 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 33102539DOI 10.3389/fvets.2020.00505PMC7498943 (free full text)PDF
     Verification: full text read; no PK numbers matched
     • Key findings · abstract:Dogs were then dosed every 12 h for 2 weeks and had further serum analyses at weeks 1 and 2, 6 h after the morning dose to assess serum cannabinoids.
     • Key findings · abstract:CBDA and THCA concentrations were 2- to 3-fold higher than CBD and THC concentrations, respectively.
     • Key findings · abstract:CBDA concentrations were statistically higher with Form 2 than the other forms, showing superior absorption/retention of CBDA.
     • Key findings · abstract:Furthermore, Form 1 showed less THCA retention than either the soft chew Form 3 or Form 2 at weeks 1 and 2.
     • Relative bioavailability · abstract:CBDA and THCA concentrations were 2- to 3-fold higher than CBD and THC concentrations, respectively.
159. Other animalDevelopment of a Novel Nano-emulsion Formulation to Improve Intestinal Absorption of Cannabidiol.
     Med Cannabis Cannabinoids, 2019 · Design: not stated · abstract only (PubMed) · open access (gold)
     PMID 34676332DOI 10.1159/000497361PMC8489317 (free full text)
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:Mean Tmax of CBD-NE was shortened significantly by the factor of 3 (from 8.00 to 2.40 h, p < 0.001) and AUC0-∞/dose increased by 65% (from 0.272 ± 0.045 to 0.448 ± 0.087 h L/kg) compared with CBD oil.
     • Key findings · abstract:AUC0-∞/dose and Cmax/dose after oral administration of CBD oil were significantly reduced by the factor of 27 and 23 (p < 0.05 and p < 0.01), respectively, in bile-fistulated rats compared with the untreated rats.
     • Cmax · abstract:AUC0-∞/dose and Cmax/dose after oral administration of CBD oil were significantly reduced by the factor of 27 and 23 (p < 0.05 and p < 0.01), respectively, in bile-fistulated rats compared with the untreated rats.
     • Tmax · abstract:Mean Tmax of CBD-NE was shortened significantly by the factor of 3 (from 8.00 to 2.40 h, p < 0.001) and AUC0-∞/dose increased by 65% (from 0.272 ± 0.045 to 0.448 ± 0.087 h L/kg) compared with CBD oil.
     • AUC · abstract:Mean Tmax of CBD-NE was shortened significantly by the factor of 3 (from 8.00 to 2.40 h, p < 0.001) and AUC0-∞/dose increased by 65% (from 0.272 ± 0.045 to 0.448 ± 0.087 h L/kg) compared with CBD oil.
     • AUC · abstract:AUC0-∞/dose and Cmax/dose after oral administration of CBD oil were significantly reduced by the factor of 27 and 23 (p < 0.05 and p < 0.01), respectively, in bile-fistulated rats compared with the untreated rats.
160. Other animalSingle-Dose Pharmacokinetics and Preliminary Safety Assessment with Use of CBD-Rich Hemp Nutraceutical in Healthy Dogs and Cats.
     Animals (Basel), 2019 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 31635105DOI 10.3390/ani9100832PMC6826847 (free full text)
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:Pharmacokinetics revealed a mean maximum concentration (Cmax) of 301 ng/mL and 43 ng/mL, area under the curve (AUC) of 1297 ng-h/mL and 164 ng-h/mL, and time to maximal concentration (Tmax) of 1.4 h and 2 h, for dogs and cats, respectively.
     • Cmax · abstract:Pharmacokinetics revealed a mean maximum concentration (Cmax) of 301 ng/mL and 43 ng/mL, area under the curve (AUC) of 1297 ng-h/mL and 164 ng-h/mL, and time to maximal concentration (Tmax) of 1.4 h and 2 h, for dogs and cats, respectively.
     • Tmax · abstract:Pharmacokinetics revealed a mean maximum concentration (Cmax) of 301 ng/mL and 43 ng/mL, area under the curve (AUC) of 1297 ng-h/mL and 164 ng-h/mL, and time to maximal concentration (Tmax) of 1.4 h and 2 h, for dogs and cats, respectively.
     • AUC · abstract:Pharmacokinetics revealed a mean maximum concentration (Cmax) of 301 ng/mL and 43 ng/mL, area under the curve (AUC) of 1297 ng-h/mL and 164 ng-h/mL, and time to maximal concentration (Tmax) of 1.4 h and 2 h, for dogs and cats, respectively.
     • Cmax · full text, Table 1:Single dose serum pharmacokinetics of 2 mg/kg oral dose of cannabidiol (CBD) enriched soft chew of individual dogs with mean and standard error. Dog Cmax (ng/mL) Tmax (h) T1/2 el. (h) AUC 0-t (ng-h/mL) MRT (h) 1 266 2 1.8 1494 2.6 2 315 1 0.5 1431 0.7 3 242 1 0.8 803 1.1 4 151 2 1.1 845 1.6 5 531 1 0.8 1912 1.2 Mean ± SEM 301 ± 63 1.4 ± 0.2 1.0 ± 0.2 1297 ± 210 1.4 ± 0.3
     • Cmax · full text, Table 2:Single dose serum pharmacokinetics of 2 mg/kg oral dosage of CBD-infused fish oil of individual cats with mean and standard error. Cat Cmax (ng/mL) Tmax (h) T1/2 elim (h) AUC 0-t (ng-h/mL) MRT (h) 1 75 1 1.2 212 2.1 2 41 1 1.3 125 2.4 3 53 1 1.7 194 2.9 4 21 4 1.7 134 5.4 5 20 1 1.7 60 2.7 6 48 4 1.2 256 5.7 Mean + SE 43 ± 9 2.0 ± 0.6 1.5 ± 0.1 164 ± 29 3.5 ± 1.4
     • Cmax · full text, Section '3.1. Pharmacokinetics':Cmax of CBD was 301 ng/mL with a Tmax of 1.4 h MRT was 1.4 h and the mean AUC was 1297 ng-h/mL.
     • Tmax · full text, Table 1:serum pharmacokinetics of 2 mg/kg oral dose of cannabidiol (CBD) enriched soft chew of individual dogs with mean and standard error. Dog Cmax (ng/mL) Tmax (h) T1/2 el. (h) AUC 0-t (ng-h/mL) MRT (h) 1 266 2 1.8 1494 2.6 2 315 1 0.5 1431 0.7 3 242 1 0.8 803 1.1 4 151 2 1.1 845 1.6 5 531 1 0.8 1912 1.2 Mean ± SEM 301 ± 63 1.4 ± 0.2 1.0 ± 0.2 1297 ± 210 1.4 ± 0.3
     • Tmax · full text, Table 2:Single dose serum pharmacokinetics of 2 mg/kg oral dosage of CBD-infused fish oil of individual cats with mean and standard error. Cat Cmax (ng/mL) Tmax (h) T1/2 elim (h) AUC 0-t (ng-h/mL) MRT (h) 1 75 1 1.2 212 2.1 2 41 1 1.3 125 2.4 3 53 1 1.7 194 2.9 4 21 4 1.7 134 5.4 5 20 1 1.7 60 2.7 6 48 4 1.2 256 5.7 Mean + SE 43 ± 9 2.0 ± 0.6 1.5 ± 0.1 164 ± 29 3.5 ± 1.4
     • Tmax · full text, Section '3.1. Pharmacokinetics':Cmax of CBD was 301 ng/mL with a Tmax of 1.4 h MRT was 1.4 h and the mean AUC was 1297 ng-h/mL.
     • AUC · full text, Table 1:of 2 mg/kg oral dose of cannabidiol (CBD) enriched soft chew of individual dogs with mean and standard error. Dog Cmax (ng/mL) Tmax (h) T1/2 el. (h) AUC 0-t (ng-h/mL) MRT (h) 1 266 2 1.8 1494 2.6 2 315 1 0.5 1431 0.7 3 242 1 0.8 803 1.1 4 151 2 1.1 845 1.6 5 531 1 0.8 1912 1.2 Mean ± SEM 301 ± 63 1.4 ± 0.2 1.0 ± 0.2 1297 ± 210 1.4 ± 0.3
     • AUC · full text, Table 2:rmacokinetics of 2 mg/kg oral dosage of CBD-infused fish oil of individual cats with mean and standard error. Cat Cmax (ng/mL) Tmax (h) T1/2 elim (h) AUC 0-t (ng-h/mL) MRT (h) 1 75 1 1.2 212 2.1 2 41 1 1.3 125 2.4 3 53 1 1.7 194 2.9 4 21 4 1.7 134 5.4 5 20 1 1.7 60 2.7 6 48 4 1.2 256 5.7 Mean + SE 43 ± 9 2.0 ± 0.6 1.5 ± 0.1 164 ± 29 3.5 ± 1.4
     • AUC · full text, Section '3.1. Pharmacokinetics':Cmax of CBD was 301 ng/mL with a Tmax of 1.4 h MRT was 1.4 h and the mean AUC was 1297 ng-h/mL.
     • Food effect · full text, Section '2.1. Dogs':All dogs had been fasted from the prior day and were not fed until 8 h after the initial dosing.
     • Food effect · full text, Section '2.2. Cats':The initial pharmacokinetic dosing was done with capsules to ensure consumption and all cats were fasted from the previous day and were not fed until 6 h after initial dosing.
161. Other animalPharmacokinetics, Safety, and Clinical Efficacy of Cannabidiol Treatment in Osteoarthritic Dogs.
     Front Vet Sci, 2018 · Design: randomized; crossover · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 30083539DOI 10.3389/fvets.2018.00165PMC6065210 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:No side effects were reported by owners, however, serum chemistry showed an increase in alkaline phosphatase during CBD treatment (p < 0.01).
     • Cmax · full text, Table 1:Serum pharmacokinetic of single oral dosing (2 mg and 8 mg/kg) of CBD oil in dogs. Cmax (ng/mL) Tmax (h) T1/2 elim (h) AUC 0-t (ng-hr/mL) MRT (h) DOSE (2 mg/kg) Dog 1 61 1 4.4 183 6.0 Dog 2 132 1 3.9 351 4.2 Dog 3 102 2 3.8 382 5.1 Dog 4 101 2 6.8 437 9.1 Median (Range) 102 (61–132.0) 1.5 (1.0–2.0) 4.2 (3.8–6.8) 367 (183–437) 5.6 (4.2–
     • Tmax · full text, Table 1:Serum pharmacokinetic of single oral dosing (2 mg and 8 mg/kg) of CBD oil in dogs. Cmax (ng/mL) Tmax (h) T1/2 elim (h) AUC 0-t (ng-hr/mL) MRT (h) DOSE (2 mg/kg) Dog 1 61 1 4.4 183 6.0 Dog 2 132 1 3.9 351 4.2 Dog 3 102 2 3.8 382 5.1 Dog 4 101 2 6.8 437 9.1 Median (Range) 102 (61–132.0) 1.5 (1.0–2.0) 4.2 (3.8–6.8) 367 (183–437) 5.6 (4.2–9.1) DOSE (8
     • AUC · full text, Table 1:Serum pharmacokinetic of single oral dosing (2 mg and 8 mg/kg) of CBD oil in dogs. Cmax (ng/mL) Tmax (h) T1/2 elim (h) AUC 0-t (ng-hr/mL) MRT (h) DOSE (2 mg/kg) Dog 1 61 1 4.4 183 6.0 Dog 2 132 1 3.9 351 4.2 Dog 3 102 2 3.8 382 5.1 Dog 4 101 2 6.8 437 9.1 Median (Range) 102 (61–132.0) 1.5 (1.0–2.0) 4.2 (3.8–6.8) 367 (183–437) 5.6 (4.2–9.1) DOSE (8 mg/kg) Dog 1 499 2 3.8
     • Food effect · full text, Section 'Pharmacokinetics':The dogs were fed 2 h after dosing.
162. Other animalPharmacokinetics of cannabidiol in dogs.
     Drug Metab Dispos, 1988 · Design: not stated · abstract only (PubMed) · unknown
     PMID 2900742
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:In the dose range of 45 to 90 mg, the increase in the AUC was proportional to the dose, a fact that indicates that the pharmacokinetic profile of CBD in this dose range was not dose dependent.
     • Key findings · abstract:In the other three, the oral bioavailability ranged from 13 to 19%.
     • AUC · abstract:In the dose range of 45 to 90 mg, the increase in the AUC was proportional to the dose, a fact that indicates that the pharmacokinetic profile of CBD in this dose range was not dose dependent.
163. Other animalPharmacokinetics of the dimethylheptyl homolog of cannabidiol in dogs.
     Drug Metab Dispos, 1988 · Design: not stated · n: N = 8 · abstract only (PubMed) · unknown
     PMID 2907468
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:DMH has a mean terminal half-life of 2 hr, its plasma levels decline in a biphasic fashion, and its total body clearance is 8.3 liters/hr.
     • Key findings · abstract:In the other four, the oral bioavailability was 3, 21, 39, and 43%, respectively.
164. In vitroAnti-convulsant efficacy of long-acting injectable cannabidiol formulation (IVL5005) in the pentylenetetrazol-induced convulsions, with pharmacokinetic characterization.
     Front Pharmacol, 2025 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 41208858DOI 10.3389/fphar.2025.1692123PMC12589995 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:IVL5005 achieved a lower maximum plasma concentration compared with oral CBD solution, potentially reducing peak concentration-related adverse effects.
     • Cmax · full text, Section 'Pharmacokinetics of CBD-loaded microsphe':In the rat PK study (Figure 2b), all five formulations, each containing 30 mg of CBD, exhibited Cmax values ranging from 41.31 to 102.53 ng/mL.
     • Cmax · full text, Section 'Pharmacokinetics of CBD-loaded microsphe':Tests #6, #7, and #9 showed relatively lower Cmax values (59.22, 41.31, and 68.96 ng/mL, respectively).
     • Cmax · full text, Section 'PK comparison between CBD solution and C':In the PO group, Cmax was reached at 8 h post-dose, followed by a rapid decline, with plasma concentrations falling below the limit of quantification by 92 h.
     • AUC · full text, Section 'Pharmacokinetics of CBD-loaded microsphe':The initial burst release, estimated by the ratio of AUClast and AUC0–24 h, was below 20% for all formulations.
     • Form comparison · full text, Section 'Seizure score distribution':On day 21, severe seizures were observed in 20%–40% of animals treated with the CBD solution, compared to 30% in the low-dose IVL5005 group and 0% in the high-dose group.
165. In vitroEnhanced oral bioavailability of cannabidiol by flexible zein nanoparticles: in vitro and pharmacokinetic studies.
     Front Nutr, 2024 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 39086540DOI 10.3389/fnut.2024.1431620PMC11289775 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:Compared with NZP-CBD, the C max of FZP-CBD at 3 different doses of CBD was increased by 1.7, 1.3 and 1.5 times respectively, and AUC0-t was increased by 1.4, 1.1 and 1.7 times respectively, bioavailability (F) was increased by 135.9%, 114.9%, 169.6% respectively.
     • Cmax · abstract:Compared with NZP-CBD, the C max of FZP-CBD at 3 different doses of CBD was increased by 1.7, 1.3 and 1.5 times respectively, and AUC0-t was increased by 1.4, 1.1 and 1.7 times respectively, bioavailability (F) was increased by 135.9%, 114.9%, 169.6% respectively.
     • AUC · abstract:Compared with NZP-CBD, the C max of FZP-CBD at 3 different doses of CBD was increased by 1.7, 1.3 and 1.5 times respectively, and AUC0-t was increased by 1.4, 1.1 and 1.7 times respectively, bioavailability (F) was increased by 135.9%, 114.9%, 169.6% respectively.
     • Cmax · full text, Section 'In vivo bioavailability':Cmax of FZP-CBD at 3 different doses of CBD was increased by 1.7, 1.3, and 1.5 times respectively, and AUC0-t was increased by 1.4, 1.1, and 1.7 times respectively, bioavailability (F) was increased by 135.9, 114.9, 169.6%, respectively (Supplementary Table S3).
     • AUC · full text, Section 'In vivo bioavailability':Cmax of FZP-CBD at 3 different doses of CBD was increased by 1.7, 1.3, and 1.5 times respectively, and AUC0-t was increased by 1.4, 1.1, and 1.7 times respectively, bioavailability (F) was increased by 135.9, 114.9, 169.6%, respectively (Supplementary Table S3).
166. Species unclearMatrix-dependent degradation kinetics and impurity fingerprinting of cannabidiol (CBD) in polymeric and lipid preservation systems.
     J Pharm Biomed Anal, 2026 · Design: not stated · abstract only (PubMed) · closed/paywalled
     PMID 41864105DOI 10.1016/j.jpba.2026.117464
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:DPPH experiments revealed that the HP-β-CD complex exhibited higher antioxidant activity (89.2%, EC₅₀ = 45.3 µg/mL) than the MCT oil system (83.6%, EC₅₀ = 58.7 µg/mL), with ascorbic acid serving as the control (EC₅₀ = 12.4 µg/mL).
     • Key findings · abstract:Additionally, photostability testing (8000 lux) demonstrated superior CBD retention in the HP-β-CD complex (>90%) compared with MCT oil (∼20%), indicating substantial light-induced degradation in the oil system.
     • Key findings · abstract:In contrast, MCT oil produced higher cannabinoid by-products (0.1-6.21%), and greater antioxidant degradation (2.5-8.6% vs 0.5-2.1%).
167. Species unclearEnhanced Stability and Oral Bioavailability of Cannabidiol in Zein and Whey Protein Composite Nanoparticles by a Modified Anti-Solvent Approach.
     Foods, 2022 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 35159526DOI 10.3390/foods11030376PMC8833932 (free full text)
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:In vivo pharmacokinetic study demonstrated that CBD in zein-WP nanoparticles displayed 2-times and 1.75-fold enhancement in maximum concentration (C max) and the area under curve (AUC) as compared to free-form CBD.
     • Cmax · abstract:In vivo pharmacokinetic study demonstrated that CBD in zein-WP nanoparticles displayed 2-times and 1.75-fold enhancement in maximum concentration (C max) and the area under curve (AUC) as compared to free-form CBD.
     • AUC · abstract:In vivo pharmacokinetic study demonstrated that CBD in zein-WP nanoparticles displayed 2-times and 1.75-fold enhancement in maximum concentration (C max) and the area under curve (AUC) as compared to free-form CBD.
     • Relative bioavailability · abstract:In vivo pharmacokinetic study demonstrated that CBD in zein-WP nanoparticles displayed 2-times and 1.75-fold enhancement in maximum concentration (C max) and the area under curve (AUC) as compared to free-form CBD.
     • Relative bioavailability · full text, Section '2.5. Encapsulation Efficiency (EE) and L':The nanoparticle suspension was mixed with acetonitrile at 9-folds volume, vortexed for 2 min, and then centrifuged at 14,000× g for 20 min.
     • Relative bioavailability · full text, Section '2.12. In Vivo Bioavailability Study':For extracting CBD, plasma samples were mixed with methanol at 3-fold volume and 5-times n-hexane, and then vortexed for 5 min.
     • Form comparison · full text, Section '3.2. Encapsulation Efficiency (EE), Load':Clearly, a significant improvement (p < 0.05) of about 465, 481, 496, and 505 folds for water solubility of CBD was observed after encapsulation in zein–WP nanoparticles as the polymer ratio grew from 1:2 to 1:5, as compared with free CBD.
168. Species unclearCannabidiol in Pharmacoresistant Epilepsy: Clinical Pharmacokinetic Data From an Expanded Access Program.
     Front Pharmacol, 2021 · Design: not stated · n: 43 patients · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 33746760DOI 10.3389/fphar.2021.637801PMC7966506 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:Results: We collected 127 plasma samples (67-morning pre-dosing and 60 post-dosing) from 43 patients (24 females, 19 males), 27 with LGS and 16 with DS.
     • Key findings · abstract:CBD median trough plasma concentration was 91 ng/ml; it doubled to 190 ng/ml 2.5 h post-dosing (p < 0.001).
     • Key findings · abstract:Cannabidiol trough plasma concentrations were linearly related to daily doses (r = 0.564, p < 0.001).
     • Key findings · abstract:Median trough CBD plasma concentration-to-weight-adjusted dose ratio (C/D) was 32% higher (p < 0.02) in plasma samples from subjects aged 18 and over than in those under 18.
     • Form comparison · full text, Section 'Results':Median trough CBD C/D ratio was 32% higher in plasma samples from patients ≥18 years (mean age 35 ± 11 years, range 18–56 years) compared with those <18 years (10 ± 4 years, range 5–17 years): 7.97 vs. 6.02, p < 0.02 (Figure 3A).
     • Form comparison · full text, Section 'Results':Both median CBD plasma concentrations (106 vs. 87 ng/ml) (Supplementary Figure S2A) and C/Ds (7.69 vs. 6.33) (Supplementary Figure S2B) did not differ between responders and nonresponders.
169. Species unclearA Systematic Review on the Pharmacokinetics of Cannabidiol in Humans.
     Front Pharmacol, 2018 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 30534073DOI 10.3389/fphar.2018.01365PMC6275223 (free full text)PDF
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:Bioavailability following smoking was 31% however no other studies attempted to report the absolute bioavailability of CBD following other routes in humans, despite i.v formulations being available.
     • Tmax · abstract:Tmax is reached between 0 and 4 h.
     • Cmax · full text, Table 1:(PK) parameters for cannabidiol (CBD). References Total n, sex Administration Source CBD dose PlasmaaPK details Other Tmax (median, range),b hrs Cmax (mean, SD)b ng/mL AUC0-t (mean, SD)b h × ng/mL AUC0-inf (mean, SD) h × ng/mL Kel (mean, SD) 1/h t1/2 (mean, SD)b h CL/F (mean, SD) L/h Mean (SD) Ohlsson et al., 1986 5, M, infrequent to frequent cannabis smokers i.v. In lab 20 mg 686 (239) ng/m
     • Cmax · full text, Section 'Cmax, Tmax, and area under the curve':The AUC0−t and Cmax of CBD is dose-dependent, and Tmax occurs between 0 and 5 h, but does not appear to be dose-dependent.
     • Cmax · full text, Section 'Oromucosal drops/spray':Oromucosal spray, either buccal, sublingual, or oropharyngeal administration, resulted in mean Cmax between 2.5 and 3.3 ng/mL and mean Tmax between 1.64 and 4.2 h.
     • Tmax · full text, Table 1:reporting pharmacokinetic (PK) parameters for cannabidiol (CBD). References Total n, sex Administration Source CBD dose PlasmaaPK details Other Tmax (median, range),b hrs Cmax (mean, SD)b ng/mL AUC0-t (mean, SD)b h × ng/mL AUC0-inf (mean, SD) h × ng/mL Kel (mean, SD) 1/h t1/2 (mean, SD)b h CL/F (mean, SD) L/h Mean (SD) Ohlsson et al., 1986 5, M, infrequent to frequent cannabis smokers i.v. In
     • Tmax · full text, Section 'Cmax, Tmax, and area under the curve':The AUC0−t and Cmax of CBD is dose-dependent, and Tmax occurs between 0 and 5 h, but does not appear to be dose-dependent.
     • Tmax · full text, Section 'Oromucosal drops/spray':Oromucosal spray, either buccal, sublingual, or oropharyngeal administration, resulted in mean Cmax between 2.5 and 3.3 ng/mL and mean Tmax between 1.64 and 4.2 h.
     • AUC · full text, Table 1:nabidiol (CBD). References Total n, sex Administration Source CBD dose PlasmaaPK details Other Tmax (median, range),b hrs Cmax (mean, SD)b ng/mL AUC0-t (mean, SD)b h × ng/mL AUC0-inf (mean, SD) h × ng/mL Kel (mean, SD) 1/h t1/2 (mean, SD)b h CL/F (mean, SD) L/h Mean (SD) Ohlsson et al., 1986 5, M, infrequent to frequent cannabis smokers i.v. In lab 20 mg 686 (239) ng/ml min × 10−3 = 16.67 (3
     • AUC · full text, Section 'Cmax, Tmax, and area under the curve':The AUC0−t and Cmax of CBD is dose-dependent, and Tmax occurs between 0 and 5 h, but does not appear to be dose-dependent.
     • AUC · full text, Section 'Oromucosal drops/spray':A dose of 20 mg/day resulted in a mean Cmax of 1.5 ng/mL and mean AUC0−t of 6.1 h × ng/mL while 60 mg/day equated to a mean Cmax of 4.8 ng/mL and AUC0−t was 38.9 h × ng/mL (Sellers et al., 2013).
     • Relative bioavailability · full text, Section 'Oral intake':The piperine-PNL oral formulation had a 4-fold increase in Cmax (2.1 ng/mL vs. 0.5 ng/mL), and a 2.2-fold increase in AUC0−t (6.9 vs. 3.1 h × ng/mL), while Tmax was decreased (1.0 vs. 3.0 h) compared to the oromucosal spray (Cherniakov et al., 2017a).
     • Food effect · full text, Table 1:, M/F 90 mg – 60 mg, 5 days 1.5 (0–6.45) 4.8 (3.4) 38.9 (33.75) 60.3 (37.71) Stott et al., 2013b 12, M Oromucosal spray (CBD and THC) GW 10 mg (fed state) 4.00 (3.02–9.02); 3.66 (2.28) 23.13 (9.29) 20.21 (8.43) 0.155 (0.089) 5.49 (2.17) 533 (318) Stott et al., 2013a 24, M Oromucosal spray (CBD and THC) GW 5 mg single dose Mean 1.00 (0.75–1.50) 0.39 (0.08) 0.82 (0.33) 1.66 (0.51) 0.173 (0.08
     • Food effect · full text, Section 'Oromucosal drops/spray':Stott et al. reported an increase in CBD bioavailability under fed vs. fasted states in 12 men after a single 10 mg dose of CBD administered through an oromucosal spray which also contained THC (Stott et al., 2013a,b).
     • Food effect · full text, Section 'Oromucosal drops/spray':Tmax was also delayed under the fed state (4.0 vs. 1.4 h).
     • Form comparison · full text, Section 'Oromucosal drops/spray':Stott et al. reported an increase in CBD bioavailability under fed vs. fasted states in 12 men after a single 10 mg dose of CBD administered through an oromucosal spray which also contained THC (Stott et al., 2013a,b).
     • Form comparison · full text, Section 'Oromucosal drops/spray':Cmax 3.7 vs. 1.2 ng/mL).
     • Form comparison · full text, Section 'Oromucosal drops/spray':Tmax was also delayed under the fed state (4.0 vs. 1.4 h).
170. HumanAntioxidants help favorably regulate the kinetics of lipid peroxidation, polyunsaturated fatty acids degradation and acidic cannabinoids decarboxylation in hempseed oil.
     Sci Rep, 2020 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 32601363DOI 10.1038/s41598-020-67267-0PMC7324387 (free full text)
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:This corresponded to a significant (p < 0.05) increase in color stability and pigment retention (chlorophyll a, chlorophyll b and carotenoids) of heated HSO.
     • Form comparison · full text, Section 'Oxidative stability and quality of therm':Results were compared with samples stored at 25 °C for 15 days (360 h).
171. RodentPharmacokinetics of Phytocannabinoid Acids and Anticonvulsant Effect of Cannabidiolic Acid in a Mouse Model of Dravet Syndrome.
     J Nat Prod, 2019 · Design: not stated · abstract only (PubMed) · open access (hybrid)
     PMID 31686510DOI 10.1021/acs.jnatprod.9b00600
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:All the phytocannabinoid acids investigated were rapidly absorbed with plasma tmax values of between 15 and 45 min and had relatively short half-lives (<4 h).
     • Key findings · abstract:The brain-plasma ratios for the acids were very low at ≤0.04.
     • Key findings · abstract:However, when CBDA was administered in an alternate Tween 80-based vehicle, it exhibited a brain-plasma ratio of 1.9.
     • Tmax · abstract:All the phytocannabinoid acids investigated were rapidly absorbed with plasma tmax values of between 15 and 45 min and had relatively short half-lives (<4 h).
     • Fractional absorption · abstract:All the phytocannabinoid acids investigated were rapidly absorbed with plasma tmax values of between 15 and 45 min and had relatively short half-lives (<4 h).
172. Other animalPhysiological effect and pharmacokinetic evaluation of combined oral administration of cannabidiolic acid and cannabigerolic acid in dogs.
     Front Vet Sci, 2026 · Design: not stated · n: 90 dogs · abstract (PubMed); full-text PDF saved · open access (gold)
     PMID 41822224DOI 10.3389/fvets.2026.1779760PMC12975459 (free full text)PDF
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:Initial single dose 24-h pharmacokinetics were performed, and from day 2-90 dogs were dosed similarly at 7 a.m. and 3 p.m. daily and serum concentrations relative to steady state were examined at days 27, 57 and 90.
     • Key findings · abstract:RESULTS: Both CBDA and CBGA were detected in the bloodstream with AUC geometric means of 1,383 ng-h/mL and 930 ng-h/mL, respectively, on 24 h pharmacokinetics assessment.
     • Key findings · abstract:THCA and CBCA were observed in the serum of dogs at significant concentrations in the 5-75 ng/mL range.
     • AUC · abstract:RESULTS: Both CBDA and CBGA were detected in the bloodstream with AUC geometric means of 1,383 ng-h/mL and 930 ng-h/mL, respectively, on 24 h pharmacokinetics assessment.
173. Other animalDifferences in Plasma Exposure of Cannabidiol and Cannabidiolic Acid Following Oral Administration to Horses.
     J Vet Pharmacol Ther, 2026 · Design: crossover · abstract only (PubMed) · open access (hybrid)
     PMID 41017237DOI 10.1111/jvp.70027PMC12796783 (free full text)
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:Observed CBDA plasma concentrations were up to 67 times higher, and the CBDA area under the plasma concentration-time curve was up to 36 times larger than those of CBD.
     • Key findings · abstract:Median terminal half-lives in plasma were 7.8 h for CBD and 5.3 h for CBDA.
     • Key findings · abstract:Both compounds were detectable in plasma for up to 72 h.
     • AUC · abstract:Observed CBDA plasma concentrations were up to 67 times higher, and the CBDA area under the plasma concentration-time curve was up to 36 times larger than those of CBD.
174. Other animalPlasma cannabinoid concentrations and transference during long-term industrial hemp administration in cattle.
     J Anim Sci, 2025 · Design: not stated · full text (Europe PMC XML) + abstract · open access (hybrid)
     PMID 41358942DOI 10.1093/jas/skaf418PMC12770982 (free full text)
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:In the present study, the plasma cannabinoid concentrations in twelve (12) Holstein steers receiving alfalfa pellet placebo (PLBO), chlortetracycline (CTC) pellets (1.1 mg/kg/d), IH (5.5 mg/kg/d CBDA;[excerpt truncated in our database — see source]
     • Key findings · abstract:Plasma samples were collected every 7 d from day -7 to 77.
     • Food effect · full text, Section 'Animals and housing':Steers were fed a custom grain mix twice daily (86.54% DM, 14.5% CP, 65.91 Mcal/cwt NEg, 0.43% calcium, 0.31% phosphorus) at 3% bodyweight per day and had ad libitum access to grass hay and water via an automated watering device during the entire study.
175. Other animalExcretion and residue depletion of cannabinoids in beef cattle fed hempseed cake for 111 days.
     Food Addit Contam Part A Chem Anal Control Expo Risk Assess, 2023 · Design: not stated · n: n = 10 · abstract only (PubMed) · closed/paywalled
     PMID 36897320DOI 10.1080/19440049.2023.2187645
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:Neutral cannabinoids (cannabinol [CBN], CBD/THC, and cannabidivarin [CBDV]) were not detected in plasma or urine, but CBD/THC was measured in adipose tissue at all withdrawal periods (6.3 ± 2.1 to 10.1 ± 2.5 ng g-1).
     • Key findings · abstract:In contrast, cannabinoid acids (cannabinolic acid [CBNA], cannabidiolic acid [CBDA]/tetrahydrocannabinolic acid [THCA], cannabichromenic acid [CBCA], and cannabidivarinic acid [CBDVA]) were sporadically detected (<15 ng mL-1) in plasma and urine of cattle fed hempseed cake.
     • Food effect · abstract:Thirty-two crossbred heifers were fed either a control diet or 20% (dry matter basis) hempseed cake in a complete ration for 111 days; of the cattle fed hempseed cake, four each were harvested with 0, 1, 4, and 8-day withdrawal periods.
     • Food effect · abstract:In contrast, cannabinoid acids (cannabinolic acid [CBNA], cannabidiolic acid [CBDA]/tetrahydrocannabinolic acid [THCA], cannabichromenic acid [CBCA], and cannabidivarinic acid [CBDVA]) were sporadically detected (<15 ng mL-1) in plasma and urine of cattle fed hempseed cake.
     • Food effect · abstract:Assessment of human exposures to CBD/THC residues through the consumption of beef fa
176. Other animalCannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations.
     Sci Rep, 2021 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 34294753DOI 10.1038/s41598-021-94212-6PMC8298633 (free full text)
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Key findings · abstract:Astonishingly, plasma cannabidiolic acid (CBDA) concentrations were 14-times higher following administration in the cannabis extract than when administered as a single molecule.
     • Cmax · full text, Table 1:CBDA, 50 mg/kg CBDVA, 7 mg/kg CBGA, 7 mg/kg THC, 15 mg/kg THCA, 50 mg/kg Extract CBD Extract CBDA Extract CBDVA Extract CBGA Extract THC Extract THCA Cmax (ng/mL) 60 ± 6 304 ± 28 47 ± 4 µg/mL 6 ± 1 µg/mL 11 ± 1 µg/mL 26 ± 2 µg/mL 12 ± 1 µg/mL 48 ± 2 µg/mL 127 ± 15 341 ± 40 465 ± 64 2094 ± 74 tmax (min) 60 90 60 90 60 15 60 120 60 90 45 30 t1/2 (min) 484 217 310 198 120 150 298 n.d 330 210 46 37 AU
     • Cmax · full text, Section 'The pharmacokinetic profiles of various ':Accordingly, the plasma Cmax value of CBDA within the full-spectrum extract (47 ± 4 µg/mL) was substantially higher than the Cmax value achieved as a single molecule (6 ± 1 µg/mL).
     • Tmax · full text, Table 1:t THCA Cmax (ng/mL) 60 ± 6 304 ± 28 47 ± 4 µg/mL 6 ± 1 µg/mL 11 ± 1 µg/mL 26 ± 2 µg/mL 12 ± 1 µg/mL 48 ± 2 µg/mL 127 ± 15 341 ± 40 465 ± 64 2094 ± 74 tmax (min) 60 90 60 90 60 15 60 120 60 90 45 30 t1/2 (min) 484 217 310 198 120 150 298 n.d 330 210 46 37 AUC (µg min/mL) 43 104 22,779 1635 3844 7459 5172 8667* 62 116 44 173
     • Tmax · full text, Section 'The pharmacokinetic profiles of various ':Absorption of the cannabinoids into plasma following oral administration of the full-spectrum extract was slow with tmax values of 45–60 min (Table 1).
     • Tmax · full text, Section 'The pharmacokinetic profiles of various ':While CBD, CBDA, CBGA and Δ9-THC were all maximally absorbed (tmax) by 60 min when administered as a full-spectrum extract, plasma tmax values were delayed (90–120 min) when each were administered individually (Fig. 1, Table 1).
     • AUC · full text, Table 1:2 µg/mL 127 ± 15 341 ± 40 465 ± 64 2094 ± 74 tmax (min) 60 90 60 90 60 15 60 120 60 90 45 30 t1/2 (min) 484 217 310 198 120 150 298 n.d 330 210 46 37 AUC (µg min/mL) 43 104 22,779 1635 3844 7459 5172 8667* 62 116 44 173
     • Form comparison · full text, Section 'The pharmacokinetic profiles of various ':In contrast, absorption of CBDVA (tmax 15 min) and Δ9-THCA (tmax 30 min) was more rapid as individual cannabinoids compared to within the full-spectrum extract (tmax values 60 and 45 min, respectively).
     • Form comparison · full text, Section 'The pharmacokinetic profiles of various ':The half-life of CBDVA, however, was slightly longer when administered as a single compound (150 min vs. 120 min).
177. Other animalPlasma concentrations of eleven cannabinoids in cattle following oral administration of industrial hemp (Cannabis sativa).
     Sci Rep, 2020 · Design: not stated · full text (Europe PMC XML) + abstract · open access (gold)
     PMID 32728233DOI 10.1038/s41598-020-69768-4PMC7391639 (free full text)
     Verification: full-text auto-extracted verbatim snippets with location; needs human check
     • Cmax · full text, Table 2:a 5.4 mg/kg dose (n = 8). Parameter Unit Geometric mean Median Range λz 1/h 0.05 0.05 0.04–0.07 T1/2 h 14.1 13.89 9.62–19.59 Tmax h 11.82 10 6.0–24.0 Cmax ng/mL 72.7 74.7 36.5–177.0 AUC0-∞ h × ng/mL 2718.6 2995.8 1217.7–5714.6 AUC0-last h × ng/mL 2593.9 2772.2 1099.7–5698.6 AUC extrapolated % 3.0 3.1 0.3–11.2 AUMC0-∞ h2 × ng/mL 83,289.8 91,850 44,793.2–156,711.1 MRT0-∞ h 30.6 29.5 25.8–37.6 MRT0-l
     • Tmax · full text, Table 2:dustrial hemp to achieve a 5.4 mg/kg dose (n = 8). Parameter Unit Geometric mean Median Range λz 1/h 0.05 0.05 0.04–0.07 T1/2 h 14.1 13.89 9.62–19.59 Tmax h 11.82 10 6.0–24.0 Cmax ng/mL 72.7 74.7 36.5–177.0 AUC0-∞ h × ng/mL 2718.6 2995.8 1217.7–5714.6 AUC0-last h × ng/mL 2593.9 2772.2 1099.7–5698.6 AUC extrapolated % 3.0 3.1 0.3–11.2 AUMC0-∞ h2 × ng/mL 83,289.8 91,850 44,793.2–156,711.1 MRT0-∞ h 3
     • AUC · full text, Table 2:ter Unit Geometric mean Median Range λz 1/h 0.05 0.05 0.04–0.07 T1/2 h 14.1 13.89 9.62–19.59 Tmax h 11.82 10 6.0–24.0 Cmax ng/mL 72.7 74.7 36.5–177.0 AUC0-∞ h × ng/mL 2718.6 2995.8 1217.7–5714.6 AUC0-last h × ng/mL 2593.9 2772.2 1099.7–5698.6 AUC extrapolated % 3.0 3.1 0.3–11.2 AUMC0-∞ h2 × ng/mL 83,289.8 91,850 44,793.2–156,711.1 MRT0-∞ h 30.6 29.5 25.8–37.6 MRT0-last h 27.6 27.0 23.4–32.1 Cl/F m
     • AUC · full text, Section 'Results':The geometric mean AUC0-∞ was 2718.6 h × ng/mL.
178. In vitroUnlocking the resorption potential of cannabidiolic acid: A comprehensive in vitro and in vivo bioavailability study.
     Int J Pharm, 2025 · Design: not stated · abstract only (PubMed) · closed/paywalled
     PMID 40858181DOI 10.1016/j.ijpharm.2025.126110
     Verification: abstract-only auto-extract; unverified
     • Key findings · abstract:In this study, the bioavailability of 10 representatives of neutral cannabinoids and cannabinoid acids was evaluated using an in vitro model of Caco-2 cells, as well as in vivo using an inbred mouse model.
179. Species unclearAlginate-based microencapsulation as a strategy to improve the therapeutic potential of cannabidiolic acid.
     Int J Pharm, 2025 · Design: not stated · abstract only (PubMed) · closed/paywalled
     PMID 39667593DOI 10.1016/j.ijpharm.2024.125076
     Verification: abstract-only auto-extract; unverified