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

Abstract

AbstractBackground and AimsLong‐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).DesignRandomised, double‐blind, placebo‐controlled, crossover experiment. The experiment was registered on ClinicalTrials.gov (NCT04851392).SettingLaboratory in London, United Kingdom.ParticipantsTwenty‐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).InterventionWe 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).MeasurementsPrimary outcomes were (i) subjective ‘feel drug effect’; (ii) verbal episodic memory (delayed prose recall); and (iii) psychotomimetic effect (Psychotomimetic States Inventory).FindingsCompared 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 [BF01] >3). There was no evidence that CBD significantly modulated the acute effects of THC.ConclusionsAdolescent 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.