BACKGROUND: Cannabidiol (CBD) is being investigated as a novel antipsychotic treatment, but its effects on psychosis are mainly drawn from pre-clinical studies, leading to uncertainty about its clinical impact.

AIMS: To evaluate the efficacy and tolerability of CBD in patients with schizophrenia spectrum disorders.

METHODS: PubMed, Scopus, Embase, PsycInfo, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and clinicaltrials.gov were searched up to July 2025. Randomized controlled trials (RCTs) of CBD in adults with schizophrenia spectrum disorders were included. Pairwise meta-analyses were conducted using random-effects models. The primary outcome was the standardized mean difference (SMD), with 95% confidence interval (95% CI), between CBD and controls at post-treatment on psychosis symptom severity. Tolerability assessment considered pooled odds ratio (OR, with 95% CI) of trial withdrawal and side effects across treatment groups.

RESULTS: A total of eight trials (six published and two unpublished), accounting for 288 participants diagnosed with psychotic disorders, were included. CBD was administered orally, at a median daily dose of 800 mg. Follow-up times ranged from 20 minutes to 12 weeks. Effect size for CBD on psychosis symptom severity was not statistically significant (SMD: -0.194; 95%CI: -0.444 to 0.056), similarly on cognitive, and psychosis positive and negative symptoms. Tolerability assessments were comparable across CBD and controls. Quality of the evidence ranged from low to very low.

CONCLUSIONS: Despite the limited number of outcomes assessed at the current state of the evidence, CBD did not show a clear benefit for psychosis symptoms in RCTs but was generally well tolerated. Larger, high-quality trials are needed to reach more robust conclusions about CBD efficacy in these disorders.