THE ACUTE EFFECTS OF CANNABIS WITH AND WITHOUT CANNABIDIOL IN ADULTS AND ADOLESCENTS: A RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSSOVER EXPERIMENT


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: (1) compare the acute effects of cannabis in adolescent and adult cannabis users, and (2) 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, 16-17 year-olds) and 24 adults (12 women, 26-29 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’ (8mg THC for 75kg person); ‘THC+CBD’ (8mg THC and 24mg CBD for 75kg 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% confidence interval (CI) 5.3 to 7.2; MD=6.8, 95% CI 6.0 to 7.7), impaired verbal 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 to 12.7; MD=10.8, 95% CI 6.2 to 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 (BF01 >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, 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.


Keywords:

CBD; Cannabis; THC; acute; adolescence; cognition; episodic memory; memory; psychosis; psychotomimetic; subjective drug effects; verbal memory.

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