Cannabidiol Increases Psychotropic Effects and Plasma Concentrations of Δ9-Tetrahydrocannabinol Without Improving Its Analgesic Properties.
Andriy A Gorbenko, Jules A A C Heuberger, Linda E Klumpers, Marieke L De Kam, Pamela K Strugala, Saco J De Visser, Geert J Groeneveld
Clinical pharmacology and therapeutics November 1, 2024 Peer reviewed DOI: 10.1002/cpt.3381 via PubMed
Summary
A high dose of cannabidiol (CBD) did not reduce the adverse effects of THC, but instead increased subjective, psychomotor, cognitive, and autonomous effects, such as feeling high by 60.5%. Lower CBD doses had no significant effect on THC's effects. CBD did not enhance THC's pain-relieving effects at any dose. High-dose CBD also increased blood levels of THC and its active metabolite. These findings do not support using CBD to improve the tolerability or pain relief of oral THC.
Study at a glance
| Design | randomized controlled trial |
|---|---|
| Sample size | 37 |
| Population | healthy volunteers |
| Key finding | Co-administration of 450 mg CBD with THC increased THC's psychoactive effects and did not enhance analgesia, contrary to the hypothesis that CBD would reduce adverse effects of THC. |
Abstract
Cannabidiol (CBD), the main non-intoxicating compound in cannabis, has been hypothesized to reduce the adverse effects of Δ9-tetrahydrocannabinol (THC), the main psychoactive and analgesic component of cannabis. This clinical trial investigated the hypothesis that CBD counteracts the adverse effects of THC and thereby potentially improves the tolerability of cannabis as an analgesic. A randomized, double-blind, placebo-controlled, five-way cross-over trial was performed in 37 healthy volunteers. On each visit, a double-placebo, THC 9 mg with placebo CBD, or THC 9 mg with 10, 30, or 450 mg CBD was administered orally. Psychoactive and analgesic effects were quantified using standardized test batteries. Pharmacokinetic sampling was performed. Data were analyzed using mixed-effects model. Co-administration of 450 mg CBD did not reduce, but instead significantly increased subjective, psychomotor, cognitive, and autonomous effects of THC (e.g., VAS "Feeling High" by 60.5% (95% CI: 12.7%, 128.5%, P < 0.01)), whereas THC effects with 10 and 30 mg CBD were not significantly 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% 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 CBD to reduce adverse effects of oral THC or enhance THC analgesia.