Does co-administration of cannabidiol (CBD) influence the plasma availability of delta-9-tetrahydrocannabinol (THC) and its active metabolite in humans? A systematic review and meta-analysis.

Lucy A Chester; Heidar Sharafi; Amani Mahroug; Daniela Ziegler; Fran&#xe7;ois-Olivier H&#xe9;bert; Didier Jutras-Aswad

doi:10.1016/j.neubiorev.2026.106910

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Does co-administration of cannabidiol (CBD) influence the plasma availability of delta-9-tetrahydrocannabinol (THC) and its active metabolite in humans? A systematic review and meta-analysis.

Lucy A Chester·Heidar Sharafi·Amani Mahroug·Daniela Ziegler·François-Olivier Hébert·Didier Jutras-Aswad

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Abstract

BACKGROUND: Research on the pharmacokinetic influence of cannabidiol (CBD) on delta-9-tetrahydrocannabinol (THC) has produced equivocal results. METHODS: We conducted a systematic search following PRISMA guidelines (last search: 24th November 2025, PROSPERO: CRD42023480695). Included studies were acute dosing trials that administered a) a single, fixed dose of THC and b) a matched dose of THC co-administered with CBD. Our objective was to investigate between-group differences in the Cmax, AUCt and AUCinf of circulating THC and its active metabolite, 11-hydroxy-THC (11-OH-THC). Hedges' g and ratio of means (RoM) were pooled from random-effects meta-analyses. The dose-effects of CBD and THC on Hedges' g were explored using meta-regression. Risk of bias was assessed using the Cochrane Collaboration tool RoB 2. RESULTS: 14 studies were included (12 crossover, two parallel group; seven oral administration, five inhalation, one IV, one mixed IV and oral; total participants: 341). In meta-analyses, average AUCt of THC was significantly higher in CBD co-administration study arms versus THC-only (Hedges' g= 0.526, 95%CI= 0.222-0.830), with very low certainty evidence. Both Cmax and AUCt of 11-OH-THC were significantly higher in CBD co-administration study arms (Cmax: g= 0.428, 0.115-0.741; AUCt: g= 0.692, 0.284-1.099), both with medium certainty evidence. In meta-regression analyses, CBD demonstrated dose effects on the Hedges' g of the Cmax and AUCt of 11-OH-THC (P < 0.05), but not THC levels. CONCLUSIONS: Cannabis users and prescribers of cannabinoid-based products should be made aware of the potential for drug-drug pharmacokinetic interactions between CBD and THC.

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Humans Cannabidiol Dronabinol Drug Interactions Meta-analysis Pharmacokinetics Systematic review Tetrahydrocannabinol Journal Article Systematic Review Meta-Analysis Review

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Lucy A Chester, Heidar Sharafi, Amani Mahroug, Daniela Ziegler, François-Olivier Hébert, Didier Jutras-Aswad. 2026-08-20. Does co-administration of cannabidiol (CBD) influence the plasma availability of delta-9-tetrahydrocannabinol (THC) and its active metabolite in humans? A systematic review and meta-analysis.. https://doi.org/10.1016/j.neubiorev.2026.106910

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Dronabinol subject Humans subject Journal Article subject Journal Article; Systematic Review; Meta-Analysis; Review resource Meta-Analysis subject Systematic reviews study pharmacokinetics subject

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