Genetic Risk for Cannabis Use Disorder Independently Linked to Schizophrenia | Research

The takeaway

Polygenic scores for cannabis use disorder predicted schizophrenia risk even in people without documented cannabis use, suggesting shared genetic factors rather than a purely causal relationship.

Anyone interested in the cannabis-psychosis debate, genetics researchers, mental health professionals

CUD genetic risk predicted schizophrenia even without cannabis use history

What the researchers found

Both cannabis use disorder and schizophrenia polygenic scores independently predicted schizophrenia diagnosis. Notably, genetic liability for cannabis use disorder was associated with schizophrenia even in individuals with no documented history of cannabis use, pointing to widespread pleiotropy (shared genetic pathways).

Why it matters

The cannabis-schizophrenia link has been debated for decades. This study used within-individual data on both genetics and diagnoses, addressing a key limitation of earlier work that lacked both measures in the same people.

The numbers in context

Cannabis use disorder polygenic scores significantly predicted schizophrenia across case definitions. The schizophrenia polygenic score effect on cannabis use was very modest. CUD genetic liability predicted schizophrenia even in people without documented cannabis use.

How the study worked

Researchers used genetic and health data from the All of Us Research Program to test whether polygenic scores for cannabis use disorder and schizophrenia independently predicted heavy cannabis use and schizophrenia diagnosis. They tested multiple case definitions to account for comorbidity.

What this study cannot tell us

Preprint (not yet peer-reviewed). Cross-sectional design can't determine temporal ordering. Cannabis use history from medical records may be incomplete. Polygenic scores explain only a fraction of genetic risk.

How to read the evidence

Moderate: large biobank with genetic and diagnostic data, but cross-sectional design and preprint status

When this study was published

2025 preprint (medRxiv, not yet peer-reviewed)

The bigger picture

The relationship between cannabis and psychosis appears to involve shared genetics, not just one causing the other. Understanding these shared pathways could reshape how clinicians assess risk for both conditions.

Questions still open

What specific genetic pathways are shared between cannabis use disorder and schizophrenia? Would these findings replicate in non-European ancestry populations?

Common questions

Does this mean cannabis doesn't cause schizophrenia?

Not exactly. The study shows shared genetic factors contribute to both conditions, but it doesn't rule out that cannabis use could also increase risk. The relationship appears more complex than simple cause and effect.

What does pleiotropy mean in this context?

Pleiotropy means the same genes influence multiple traits. Here, some of the same genetic variants that increase risk for cannabis use disorder also increase risk for schizophrenia, independent of actual cannabis use.

Read the original research

Investigating the Polygenic Relationship Between Cannabis Use and Schizophrenia in the All of Us Research Program.

medRxiv : the preprint server for health sciences

View on PubMed ↗Publisher’s paper ↗

Citation

Austin-Zimmerman, Isabelle; Thorpe, Hayley Ha; Meredith, John J; Khokhar, Jibran; Ge, Tian; Di Forti, Marta; Agrawal, Arpana; Johnson, Emma C; Sanchez-Roige, Sandra. (2025). Investigating the Polygenic Relationship Between Cannabis Use and Schizophrenia in the All of Us Research Program.. medRxiv : the preprint server for health sciences. https://doi.org/10.1101/2025.05.20.25327979