Does cannabidiol reduce the adverse effects of cannabis in schizophrenia? A randomised, double-blind, cross-over trial
Edward Chesney 1 2 3, Dominic Oliver 4 5, Ananya Sarma 6, Ayşe Doğa Lamper 6, Ikram Slimani 6, Millie Lloyd 6, Alex M Dickens 7 8, Michael Welds 9, Matilda Kråkström 7 8, Irma Gasparini-Andre 6, Matej Orešič 7 8 10, Will Lawn 11, Natavan Babayeva 9, Tom P Freeman 12, Amir Englund 13, John Strang 13 9, Philip McGuire 4 5
- 1Department of Addictions, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK. edward.chesney@kcl.ac.uk.
- 2Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK. edward.chesney@kcl.ac.uk.
- 3South London and Maudsley NHS Foundation Trust, London, UK. edward.chesney@kcl.ac.uk.
- 4Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
- 5NIHR Oxford Health Biomedical Research Centre, Oxford, UK.
- 6Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK.
- 7Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
- 8Department of Life Technologies, University of Turku, Turku, Finland.
- 9South London and Maudsley NHS Foundation Trust, London, UK.
- 10School of Medical Sciences, Örebro University, Örebro, Sweden.
- 11Department of Psychology, Institute of Psychiatry Psychology and Neuroscience, King’s College London, London, UK.
- 12Addiction and Mental Health Group (AIM), Department of Psychology, University of Bath, Bath, UK.
- 13Department of Addictions, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK.
Affiliationer
In patients with schizophrenia, cannabis use exacerbates symptoms and can lead to a relapse of psychosis. Some experimental studies in healthy volunteers suggest that pre-treatment with cannabidiol (CBD) may reduce these effects, but others do not. Here, we investigated whether pre-treatment with CBD ameliorates the acute adverse effects of cannabis in patients with schizophrenia. Participants (n = 30) had schizophrenia or schizoaffective disorder plus a comorbid cannabis use disorder. In a double-blind, randomised, placebo-controlled, crossover trial, participants received oral CBD 1000 mg or placebo three hours before inhaling vaporised cannabis (containing Δ9-tetrahydrocannabinol (THC) 20-60 mg). The primary outcome was delayed verbal recall measured with the Hopkins Verbal Learning Test-Revised. We also measured psychotic symptoms with the Positive and Negative Syndrome Scale (PANSS) – positive subscale. Delayed verbal recall after cannabis administration was 3.5 words (95% confidence interval [CI]: 2.5-4.5) following pre-treatment with CBD, compared to 4.8 words (95% CI: 3.9 to 5.8) following pre-treatment with placebo (mean difference [MD] = -1.3 [95% CI: -2.0 to -0.6]; p = 0.001). After CBD pre-treatment, inhalation of cannabis was associated with an increase in PANSS-P score of 5.0 (95% CI: 3.6 to 6.5), compared to 2.9 (95% CI: 1.5 to 4.3) following pre-treatment with placebo (MD = 2.2 [95% CI: 0.6 to 3.7]; p = 0.01). Administration of CBD did not have a significant effect on plasma concentration of THC or its active metabolite, 11-hydroxy-THC. In patients with schizophrenia and a comorbid cannabis use disorder, pre-treatment with CBD did not attenuate the acute effects of cannabis on memory impairment or psychotic symptoms, but appeared to exacerbate them. The study was registered on Clinicaltrials.gov
