Cannabidiol Increases Psychotropic Effects and Plasma Concentrations of Δ9‐Tetrahydrocannabinol Without Improving Its Analgesic Properties

• Published in: Clinical pharmacology and therapeutics 2024-11, Vol.116 (5), p.1289-1303
• Main Authors: Gorbenko, Andriy A., Heuberger, Jules A.A.C., Klumpers, Linda E., Kam, Marieke L., Strugala, Pamela K., Visser, Saco J., Groeneveld, Geert J.
• Format: Article
• Language: English
• ISSN: 0009-9236; 1532-6535; 1532-6535
• DOI: 10.1002/cpt.3381

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