Cannabidiol for the treatment of positive and negative symptoms in schizophrenia spectrum disorders: a systematic review and meta-analysis

Background: Cannabidiol (CBD) has shown therapeutic potential as an antipsychotic in preclinical studies, although the pharmacodynamics profile remains to be fully explained. Current research focuses on CBD as an adjunctive strategy, a design that allows addressing residual symptoms while avoiding the ethical and clinical risks associated with discontinuing standard antipsychotic medication. This systematic review and meta-analysis evaluated the efficacy of CBD as an adjunctive therapy for positive and negative symptoms in schizophrenia spectrum disorders. Methods: PubMed and CENTRAL were searched up to May 14, 2025. We included randomized controlled trials (RCTs) comparing CBD augmentation to placebo in adults with these disorders. Primary outcomes were changes on the Positive and Negative Syndrome Scale (PANSS). Results: Five RCTs were included. Meta-analysis showed a statistically significant advantage for CBD over placebo for PANSS total scores (Mean Difference, MD -1.91; 95% Confidence Interval, CI -3.726 to -0.102), positive subscale (MD -1.304; CI -1.917 to -0.692), and general subscale (MD -1.094; CI -1.57 to -0.618). No significant effect was found for the negative subscale. Dropout rates were not significantly different (Odds Ratio, OR 0.93; 95% CI 0.55 to 1.59). Heterogeneity was low across outcomes. Conclusion: Our findings demonstrate a statistically significant, albeit small, advantage for adjunctive CBD over placebo for total, positive, and general symptoms in schizophrenia. The lack of effect on negative symptoms suggests a targeted mechanism. Given the consistency across studies, adjunctive CBD is a promising option for specific symptom clusters, but its clinical impact requires confirmation in larger trials.