Genetic overlap between cannabis use and psychotic disorders suggests shared biological roots | Research

The takeaway

A Lancet Psychiatry study found shared genetic architecture between cannabis use and schizophrenia/bipolar disorder, with causal evidence running in both directions.

Psychiatric geneticists, psychosis researchers, genetic epidemiologists

Genetic correlations of 0.22-0.35 between cannabis phenotypes and psychotic disorders

What the researchers found

Genome-wide genetic correlations between psychotic disorders and cannabis phenotypes ranged from 0.22-0.35. Causal analysis showed psychotic disorders had a causal effect on cannabis phenotypes, and lifetime cannabis use had a causal effect on bipolar disorder. Polygenic scores for cannabis predicted psychotic disorders independently. Shared loci implicated neuronal cells and drug-gene targets for nicotine, alcohol, and duloxetine.

Why it matters

Published in Lancet Psychiatry, this study provides the most comprehensive genetic evidence to date that the cannabis-psychosis relationship involves shared biological vulnerability, not just one causing the other.

The numbers in context

Genetic correlations 0.22-0.35; 3-27 shared loci per phenotype pair; 2,181 participants in polygenic score analyses (400 bipolar, 697 schizophrenia, 1,044 controls); 48.6% female; mean age 33.1 years

How the study worked

Genome-wide association summary statistics from European ancestry (Psychiatric Genomics Consortium, UK Biobank, International Cannabis Consortium). Included heritability estimation, genetic correlations, shared loci identification, causal analyses, and polygenic risk score analyses using the Norwegian Thematically Organized Psychosis cohort (n=2,181).

What this study cannot tell us

Limited to European ancestry populations. Mendelian randomization assumptions may not fully hold. Cannot identify specific causal mechanisms. Shared GWAS loci do not necessarily mean shared functional pathways.

How to read the evidence

Large-scale genetic analysis published in a top-tier journal using multiple complementary methods, though limited to European ancestry.

When this study was published

Published 2023

The bigger picture

The bidirectional causal findings suggest that some individuals are genetically predisposed to both cannabis use and psychotic disorders, supporting targeted prevention in those with high genetic risk rather than population-wide approaches.

Questions still open

Could genetic risk scores be used clinically to identify individuals who should avoid cannabis? Do the shared loci suggest novel treatment targets for both conditions?

Common questions

Is the link between cannabis and psychosis genetic?

Partly. This study found significant genetic overlap between cannabis use and schizophrenia/bipolar disorder, with shared loci and bidirectional causal effects, suggesting shared biological vulnerability.

Does cannabis cause psychosis or do people with psychosis use more cannabis?

Both appear to be true. Causal analysis showed psychotic disorders increased cannabis use, and lifetime cannabis use had a causal effect on bipolar disorder specifically. The relationship runs in both directions.

Read the original research

The relationship between cannabis use, schizophrenia, and bipolar disorder: a genetically informed study.

The lancet. Psychiatry, 10(6), 441-451

View on PubMed ↗Publisher’s paper ↗

Citation

Cheng, Weiqiu; Parker, Nadine; Karadag, Naz; Koch, Elise; Hindley, Guy; Icick, Romain; Shadrin, Alexey; O'Connell, Kevin S; Bjella, Thomas; Bahrami, Shahram; Rahman, Zillur; Tesfaye, Markos; Jaholkowski, Piotr; Rødevand, Linn; Holen, Børge; Lagerberg, Trine Vik; Steen, Nils Eiel; Djurovic, Srdjan; Dale, Anders M; Frei, Oleksandr; Smeland, Olav B; Andreassen, Ole A. (2023). The relationship between cannabis use, schizophrenia, and bipolar disorder: a genetically informed study.. The lancet. Psychiatry, 10(6), 441-451. https://doi.org/10.1016/S2215-0366(23)00143-8