Cannabis Use in Schizophrenia: More Positive Symptoms, Fewer Negative Symptoms in Large Meta-Analysis | Research

The takeaway

An individual participant data meta-analysis of 3,053 patients found cannabis use in schizophrenia was associated with higher positive symptoms, higher excitement, and lower negative symptoms, with no association with depression or disorganization.

Psychiatrists treating schizophrenia and researchers studying the cannabis-psychosis relationship

3,053 patients from 21 datasets

What the researchers found

Cannabis use was associated with higher positive symptom severity (aMD=0.38), lower negative symptom severity (aMD=-0.50), and higher excitement (aMD=0.16) using the 5-factor PANSS model. No significant associations were found with disorganization or depression dimensions. Effect sizes were small and confidence intervals wide.

Why it matters

This is the largest IPDMA on cannabis and schizophrenia symptoms to date. The finding that cannabis use is associated with lower negative symptoms (amotivation, flat affect) alongside higher positive symptoms (hallucinations, delusions) creates a complex picture with implications for treatment.

The numbers in context

3,053 complete cases from 21 datasets; positive symptoms aMD=0.38 (95% CI: 0.08-0.63); negative symptoms aMD=-0.50 (95% CI: -0.91 to -0.08); excitement aMD=0.16 (95% CI: 0.03-0.28); no association with depression or disorganization

How the study worked

Individual participant data meta-analysis (IPDMA) using raw datasets from 21 studies totaling 3,053 complete cases. PubMed, ScienceDirect, and PsycINFO searched through September 2022. Cannabis users required to have CUD diagnosis or use at least twice weekly. Outcomes assessed using both 3-factor and 5-factor PANSS structures with adjusted multivariate analysis.

What this study cannot tell us

Cross-sectional associations cannot determine causation. Effect sizes are small with wide confidence intervals. Cannot rule out that people with fewer negative symptoms are simply more socially active and therefore more likely to access cannabis. Self-selection bias remains.

How to read the evidence

Large IPDMA using raw data with adjusted analysis, the gold standard for meta-analyses, though underlying studies were cross-sectional

When this study was published

2023 study

The bigger picture

The lower negative symptoms associated with cannabis use could explain why some patients report subjective benefit from cannabis, as negative symptoms (social withdrawal, emotional flatness) are often the most distressing and treatment-resistant aspects of schizophrenia. However, the increased positive symptoms suggest this comes at a cost.

Questions still open

Do patients with fewer negative symptoms use cannabis because they are more socially connected, or does cannabis reduce negative symptoms? Could targeted cannabinoid therapies help negative symptoms without worsening positive symptoms? Would longitudinal data clarify the direction of these associations?

Common questions

Does cannabis make schizophrenia symptoms worse?

It is more nuanced than that. This meta-analysis found cannabis use was associated with more positive symptoms (hallucinations, delusions) but fewer negative symptoms (social withdrawal, emotional flatness). The effect sizes were small.

Why might cannabis reduce negative symptoms in schizophrenia?

The authors note this could reflect either a direct effect of cannabis on negative symptoms or self-selection, where patients with fewer negative symptoms are more socially engaged and therefore more likely to use cannabis. The study cannot distinguish between these explanations.

Read the original research

Association between cannabis use and symptom dimensions in schizophrenia spectrum disorders: an individual participant data meta-analysis on 3053 individuals.

EClinicalMedicine, 64, 102199

View on PubMed ↗Publisher’s paper ↗

Citation

Argote, Mathilde; Sescousse, Guillaume; Brunelin, Jérôme; Baudin, Grégoire; Schaub, Michael Patrick; Rabin, Rachel; Schnell, Thomas; Ringen, Petter Andreas; Andreassen, Ole Andreas; Addington, Jean Margaret; Brambilla, Paolo; Delvecchio, Giuseppe; Bechdolf, Andreas; Wobrock, Thomas; Schneider-Axmann, Thomas; Herzig, Daniela; Mohr, Christine; Vila-Badia, Regina; Rodie, Judith Usall; Mallet, Jasmina; Ricci, Valerio; Martinotti, Giovanni; Knížková, Karolína; Rodriguez, Mabel; Cookey, Jacob; Tibbo, Philip; Scheffler, Freda; Asmal, Laila; Garcia-Rizo, Clemente; Amoretti, Silvia; Huber, Christian; Thibeau, Heather; Kline, Emily; Fakra, Eric; Jardri, Renaud; Nourredine, Mikail; Rolland, Benjamin. (2023). Association between cannabis use and symptom dimensions in schizophrenia spectrum disorders: an individual participant data meta-analysis on 3053 individuals.. EClinicalMedicine, 64, 102199. https://doi.org/10.1016/j.eclinm.2023.102199