Does cannabidiol make cannabis safer? A randomised, double-blind, cross-over trial of cannabis with four different CBD:THC ratios

Amir Englund, Dominic Oliver, Edward Chesney, Lucy Chester, Jack Wilson, Simina Sovi, Andrea De Micheli, John Hodsoll, Paolo Fusar-Poli, John Strang, Robin M. Murray, Tom P. Freeman, Philip McGuire

Research output: Contribution to journalArticlepeer-review

28 Citations (SciVal)

Abstract

As countries adopt more permissive cannabis policies, it is increasingly important to identify strategies that can reduce the harmful effects of cannabis use. This study aimed to determine if increasing the CBD content of cannabis can reduce its harmful effects. Forty-six healthy, infrequent cannabis users participated in a double-blind, within-subject, randomised trial of cannabis preparations varying in CBD content. There was an initial baseline visit followed by four drug administration visits, in which participants inhaled vaporised cannabis containing 10 mg THC and either 0 mg (0:1 CBD:THC), 10 mg (1:1), 20 mg (2:1), or 30 mg (3:1) CBD, in a randomised, counter-balanced order. The primary outcome was change in delayed verbal recall on the Hopkins Verbal Learning Task. Secondary outcomes included change in severity of psychotic symptoms (e.g., Positive and Negative Syndrome Scale [PANSS] positive subscale), plus further cognitive, subjective, pleasurable, pharmacological and physiological effects. Serial plasma concentrations of THC and CBD were measured. THC (0:1) was associated with impaired delayed verbal recall (t(45) = 3.399, d = 0.50, p = 0.001) and induced positive psychotic symptoms on the PANSS (t(45) = −4.709, d = 0.69, p = 2.41 × 10–5). These effects were not significantly modulated by any dose of CBD. Furthermore, there was no evidence of CBD modulating the effects of THC on other cognitive, psychotic, subjective, pleasurable, and physiological measures. There was a dose-response relationship between CBD dose and plasma CBD concentration, with no effect on plasma THC concentrations. At CBD:THC ratios most common in medicinal and recreational cannabis products, we found no evidence that CBD protects against the acute adverse effects of cannabis. This should be considered in health policy and safety decisions about medicinal and recreational cannabis.

Original languageEnglish
Pages (from-to)869–876
Number of pages8
JournalNeuropsychopharmacology
Volume48
Issue number6
Early online date16 Nov 2022
DOIs
Publication statusPublished - 31 May 2023

Bibliographical note

Funding Information:
This study was fully funded by a Research Grant from the Medical Research Council UK (MR/P006841/1). The funder had no involvement in the design, data collection, analysis, interpretation, write up or the decision of where to publish. AE, LC, JH, RMM, and JS are part-funded or supported by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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