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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 & Therapeutics November 1, 2024 DOI: 10.1002/cpt.3381 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized, double-blind, placebo-controlled, five-way cross-over trial Peer reviewed
Sample size 37
Population Healthy volunteers
Interventions THC 9 mg with placebo CBD double-placebo
Dose THC 9 mg; CBD 10, 30, or 450 mg
Topics Cannabis CBD
Citations 17
Key findings Co-administration of 450 mg CBD significantly increased the psychoactive effects of THC and did not enhance THC analgesia, contrary to the hypothesis that CBD would reduce adverse effects.

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.

Comparable studies

Other randomized controlled trials on CBD, most cited first.

Study Year Design Participants
Cannabidiol inhibits THC-elicited paranoid symptoms and hippocampal-dependent memory impairment Healthy participants 2012 Randomized controlled trial n = 48
Distinct Effects of Δ9-Tetrahydrocannabinol and Cannabidiol on Neural Activation During Emotional Processing Healthy, English-native, right-handed men who had used cannabis 15 times or less in... 2009 Double-blind, randomized, placebo-controlled crossover trial n = 15
Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life Healthy subjects aged 18 to 35 years 2017 Randomized controlled trial n = 60
Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers Healthy male subjects 2012 Randomized controlled trial n = 16
Modulation of Mediotemporal and Ventrostriatal Function in Humans by Δ9-Tetrahydrocannabinol Healthy, native English-speaking, right-handed men of white race/ethnicity who had used... 2009 Randomized controlled trial n = 15

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