The acute effects of cannabis with and without cannabidiol in adults and adolescents: A randomised, double‐blind, placebo‐controlled, crossover experiment

Adolescent cannabis users are neither more resilient nor more vulnerable than adult cannabis users to the acute psychotomimetic, verbal memory-impairing, or subjective effects of cannabis. In a randomized, double-blind, placebo-controlled crossover experiment with 24 adolescents (16-17 years old) and 24 adults (26-29 years old) who used cannabis 0.5-3 days per week, vaporized THC (8 mg for a 75 kg person) and THC plus CBD (24 mg) both significantly increased subjective drug effect, impaired verbal episodic memory, and increased psychotomimetic effects compared to placebo. There was no evidence that adolescents differed from adults in their responses, and CBD did not modulate the acute effects of THC.

Study at a glance

Abstract

Abstract Background and Aims Long‐term harms of cannabis may be exacerbated in adolescence, but little is known about the acute effects of cannabis in adolescents. We aimed to (i) compare the acute effects of cannabis in adolescent and adult cannabis users and (ii) determine if cannabidiol (CBD) acutely modulates the effects of delta‐9‐tetrahydocannabinol (THC). Design Randomised, double‐blind, placebo‐controlled, crossover experiment. The experiment was registered on ClinicalTrials.gov (NCT04851392). Setting Laboratory in London, United Kingdom. Participants Twenty‐four adolescents (12 women, 16‐ to 17‐year‐olds) and 24 adults (12 women, 26‐ to 29‐year‐olds) who used cannabis 0.5–3 days/week and were matched on cannabis use frequency (mean = 1.5 days/week). Intervention We administered three weight‐adjusted vaporised cannabis flower preparations: ‘THC’ (8 mg THC for 75 kg person); ‘THC + CBD’ (8 mg THC and 24 mg CBD for 75 kg person); and ‘PLA’ (matched placebo). Measurements Primary outcomes were (i) subjective ‘feel drug effect’; (ii) verbal episodic memory (delayed prose recall); and (iii) psychotomimetic effect (Psychotomimetic States Inventory). Findings Compared with ‘PLA’, ‘THC’ and ‘THC + CBD’ significantly ( P < 0.001) increased ‘feel drug effect’ (mean difference [MD] = 6.3, 95% CI = 5.3–7.2; MD = 6.8, 95% CI = 6.0–7.7), impaired verbal episodic memory (MD = –2.7, 95% CI = −4.1 to −1.4; MD = −2.9, 95% CI = −4.1 to −1.7) and increased psychotomimetic effects (MD = 7.8, 95% CI = 2.8–12.7; MD = 10.8, 95% CI = 6.2–15.4). There was no evidence that adolescents differed from adults in their responses to cannabis (interaction P ≥ 0.4). Bayesian analyses supported equivalent effects of cannabis in adolescents and adults (Bayes factor [BF 01 ] >3). There was no evidence that CBD significantly modulated the acute effects of THC. Conclusions Adolescent cannabis users are neither more resilient nor more vulnerable than adult cannabis users to the acute psychotomimetic, verbal memory‐impairing or subjective effects of cannabis. Furthermore, in adolescents and adults, vaporised cannabidiol does not mitigate the acute harms caused by delta‐9‐tetrahydocannabinol.