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 Chester, Heidar Sharafi, Amani Mahroug, Daniela Ziegler, François-Olivier Hebert, Didier Jutras-Aswad
Neuroscience & Biobehavioral Reviews August 20, 2026 DOI: 10.1016/j.neubiorev.2026.106910 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Peer reviewed |
|---|---|
| Sample size | 341 |
| Population | Participants in acute dosing trials of THC with or without co-administered CBD (12 crossover, two parallel group; oral, inhalation, IV, and mixed routes) |
| Interventions | Cannabidiol (CBD) Tetrahydrocannabinol (THC) |
| Measures | Cmax, AUCt, AUCinf |
| Topics | Cannabis CBD |
| Keywords | Meta-analysis Pharmacokinetics Systematic review |
| Key findings | Pooled analyses indicate that CBD co-administration significantly increased average THC AUCt (Hedges' g = 0.526) and significantly increased both Cmax and AUCt of the active metabolite 11-OH-THC (g = 0.428 and 0.692), with very low to medium certainty evidence. Meta-regression suggested CBD dose effects on 11-OH-THC Cmax and AUCt but not on THC levels. The authors conclude that users and prescribers should be aware of potential CBD-THC pharmacokinetic interactions. |
Abstract
Research on the pharmacokinetic influence of cannabidiol (CBD) on delta-9-tetrahydrocannabinol (THC) has produced equivocal results. 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. 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. Cannabis users and prescribers of cannabinoid-based products should be made aware of the potential for drug-drug pharmacokinetic interactions between CBD and THC.
Comparable studies
Other systematic reviews and meta-analyses on CBD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neuroimaging in cannabis use: a systematic review of the literature Cannabis users and controls in neuroimaging studies | 2009 | Systematic review | |
| Cannabis, a cause for anxiety? A critical appraisal of the anxiogenic and anxiolytic properties | 2020 | Systematic review | |
| Effects of Cannabis on Impulsivity: A Systematic Review of Neuroimaging Findings | 2014 | Systematic review | |
| Association between formal thought disorder and cannabis use: a systematic review and meta-analysis Individuals along the psychosis continuum (healthy individuals, patients with... | 2022 | Meta-analysis | n = 5,191 |
| The Relationship Between Cannabis Use and Schizophrenia As a Risk Factor or For Its Therapeutic Potential: A Systematic Review of Evidence | 2025 | Systematic review |
Citations in the library
Cites 17
- Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Journal of Psychopharmacology October 5, 2012
- Cannabidiol (CBD) content in vaporized cannabis does not prevent tetrahydrocannabinol (THC)-induced impairment of driving and cognition Psychopharmacology May 1, 2019
- Dissociable effects of cannabis with and without cannabidiol on the human brain’s resting-state functional connectivity Journal of Psychopharmacology April 23, 2019
- Sex differences in acute cannabis effects revisited: Results from two randomized, controlled trials Addiction Biology December 22, 2021
- The acute effects of cannabis with and without cannabidiol in adults and adolescents: A randomised, double‐blind, placebo‐controlled, crossover experiment Addiction February 8, 2023
and 12 more in the library