Does cannabidiol reduce the adverse effects of cannabis in schizophrenia? A randomised, double-blind, cross-over trial.
Edward Chesney, Dominic Oliver, Ananya Sarma, Ayşe Doğa Lamper, Ikram Slimani, Millie Lloyd, Alex M. Dickens, Michael Welds, Matilda Kråkström, Irma Gasparini-Andre, Matej Orešič, Will Lawn, Natavan Babayeva, Tom P. Freeman, Amir Englund, John Strang, Philip Mcguire
Neuropsychopharmacology November 2025 DOI: 10.1038/s41386-025-02175-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, randomised, placebo-controlled, crossover trial Randomized Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Patients with schizophrenia or schizoaffective disorder plus a comorbid cannabis use disorder |
| Intervention | Cannabidiol (CBD) |
| Dose | oral CBD 1000 mg; vaporised cannabis containing THC 20-60 mg |
| Measures | Hopkins Verbal Learning Test-Revised, Positive and Negative Syndrome Scale (PANSS) - positive subscale |
| Topics | Cannabis CBD |
| Registration | NCT04605393 |
| Key findings | Pre-treatment with oral CBD 1000 mg did not attenuate the acute adverse effects of vaporized cannabis on memory or psychotic symptoms in patients with schizophrenia and comorbid cannabis use disorder, and appeared to exacerbate them: delayed verbal recall was lower after CBD than placebo, and cannabis-related increases in PANSS positive symptoms were larger after CBD than placebo. |
Abstract
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 (NCT04605393).
Comparable studies
Other randomized controlled trials on CBD, most cited first.
Citations in the library
Cited by 3
- The Potential of Cannabidiol for the Treatment of Psychosis: Endocannabinoid Regulation of Serotonergic Neurotransmission via Serotonin 5-HT1A/2A Receptors. Neurochemical Research August 27, 2026
- Cannabis and Mental Health: A Review. JAMA Internal Medicine May 1, 2026
- Effect of caffeine and cannabidiol (CBD) co-administration on Δ9-tetrahydrocannabinol (Δ9-THC) subjective effects, performance impairment, and pharmacokinetics. Neuropsychopharmacology November 1, 2025
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and 15 more in the library