Effect of four-week cannabidiol treatment on cognitive function: secondary outcomes from a randomised clinical trial for the treatment of cannabis use disorder

Rachel Lees, Lindsey A Hines, Chandni Hindocha, Gianluca Baio, Natacha D C Shaban, George Stothart, Ali Mofeez, Celia J A Morgan, H Valerie Curran, Tom P Freeman

Research output: Contribution to journalArticlepeer-review

4 Citations (SciVal)


RATIONALE: Chronic cannabis use is associated with impaired cognitive function. Evidence indicates cannabidiol (CBD) might be beneficial for treating cannabis use disorder. CBD may also have pro-cognitive effects; however, its effect on cognition in people with cannabis use disorder is currently unclear.

OBJECTIVES: We aimed to assess whether a 4-week CBD treatment impacted cognitive function. We hypothesised that CBD treatment would improve cognition from baseline to week 4, compared to placebo.

METHODS: Cognition was assessed as a secondary outcome in a phase 2a randomised, double-blind, parallel-group and placebo-controlled clinical trial of 4-week daily 200 mg, 400 mg and 800 mg CBD for the treatment of cannabis use disorder. Participants had moderate or severe DSM-5 cannabis use disorder and intended to quit cannabis use. Our pre-registered primary cognitive outcome was delayed prose recall. Secondary cognitive outcomes were immediate prose recall, stop signal reaction time, trail-making task performance, verbal fluency and digit span.

RESULTS: Seventy participants were randomly assigned to placebo (n = 23), 400 mg CBD (n = 24) and 800 mg CBD (n = 23). A 200 mg group was eliminated from the trial because it was an inefficacious dose at interim analysis (n = 12) and was not analysed here. For the primary cognitive outcome, there was no effect of CBD compared to placebo, evidenced by a lack of dose-by-time interaction at 400 mg (0.46, 95%CIs: - 1.41, 2.54) and 800 mg (0.89, 95%CIs: - 0.99, 2.81). There was no effect of CBD compared to placebo on secondary cognitive outcomes, except backwards digit span which increased following 800 mg CBD (0.30, 95%CIs: 0.02, 0.58).

CONCLUSIONS: In this clinical trial for cannabis use disorder, CBD did not influence delayed verbal memory. CBD did not have broad cognitive effects but 800 mg daily treatment may improve working memory manipulation.

CLINICAL TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov (NCT02044809) and the EU Clinical Trials Register (2013-000,361-36).

Original languageEnglish
Pages (from-to)337-346
Number of pages10
Issue number2
Early online date4 Jan 2023
Publication statusPublished - 28 Feb 2023

Bibliographical note

Funding Information:
The trial was supported by a UK Medical Research Council Developmental Pathway Funding Scheme award (MR/K015524/1). The funder played no role in the collection, analysis or interpretation of data, writing of the report or the decision to submit for publication. This work was supported in part by grant MR/N0137941/1 for the GW4 BIOMED MRC DTP, awarded to the Universities of Bath, Bristol, Cardiff, and Exeter from the Medical Research Council (MRC)/UKRI.


  • Humans
  • Cannabidiol/pharmacology
  • Marijuana Abuse/complications
  • Hallucinogens/pharmacology
  • Substance-Related Disorders/drug therapy
  • Cannabis/adverse effects
  • Cognition
  • Double-Blind Method

ASJC Scopus subject areas

  • Pharmacology


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