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

Will Lawn; Katie Trinci; Claire Mokrysz; Anna Borissova; Shelan Ofori; Kat Petrilli; Michael Bloomfield; Zarah R Haniff; Daniel Hall; Natalia Fernandez-Vinson; Simiao Wang; Amir Englund; Edward Chesney; Matthew B Wall; Tom P Freeman; H Valerie Curran

doi:10.1111/add.16154

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

Addiction. 2023 Jul;118(7):1282-1294. doi: 10.1111/add.16154. Epub 2023 Feb 26.

Authors

Will Lawn^{1

2

3}, Katie Trinci³, Claire Mokrysz³, Anna Borissova^{4

5}, Shelan Ofori³, Kat Petrilli⁶, Michael Bloomfield^{3

5

7}, Zarah R Haniff³, Daniel Hall³, Natalia Fernandez-Vinson³, Simiao Wang^{2

3}, Amir Englund^{2

8}, Edward Chesney^{2

8}, Matthew B Wall^{3

9}, Tom P Freeman^{3

6}, H Valerie Curran³

Affiliations

¹ Department of Psychology, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
² Department of Addictions, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
³ Clinical Psychopharmacology Unit, Clinical Educational and Health Psychology, University College London, London, UK.
⁴ Department of Neuroimaging, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
⁵ NIHR University College London Hospitals Biomedical Research Centre, University College Hospital, London, UK.
⁶ Addiction and Mental Health Group (AIM), Department of Psychology, University of Bath, Bath, UK.
⁷ Translational Psychiatry Research Group, Research Department of Mental Health Neuroscience, Division of Psychiatry, University College London, London, UK.
⁸ Department of Psychosis Studies, Institute of Psychiatry Psychology and Neuroscience, King's College London, London, UK.
⁹ Invicro London, Burlington Danes Building, Hammersmith Hospital, Du Cane Road, London, UK.

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 [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, 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.

Keywords: CBD; THC; adolescence; cannabis; cognition; memory; psychosis; subjective drug effects.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Bayes Theorem
Cannabidiol*
Cannabinoid Receptor Agonists
Cannabis*
Cross-Over Studies
Double-Blind Method
Dronabinol
Female
Hallucinogens*
Humans
Marijuana Smoking*

Substances

Cannabidiol
Dronabinol
Hallucinogens
Cannabinoid Receptor Agonists

Associated data

ClinicalTrials.gov/NCT04851392

Grants and funding

MR/P012728/1/MRC_/Medical Research Council/United Kingdom