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 1 , Heidar Sharafi 2 , Amani Mahroug 1 , Daniela Ziegler 3 , François-Olivier Hébert 2 , Didier Jutras-Aswad 4
- 1Research Centre, Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada; Department of Psychiatry and Addiction, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.
- 2Research Centre, Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada.
- 3Centre hospitalier de l’Université de Montréal, Montréal, QC, Canada.
- 4Research Centre, Centre Hospitalier de l’Université de Montréal, Montréal, QC, Canada; Department of Psychiatry and Addiction, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada. Electronic address: didier.jutras-aswad@umontreal.ca.
Affiliationer
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.
Keywords: Cannabidiol; Meta-analysis; Pharmacokinetics; Systematic review; Tetrahydrocannabinol.
