People with psychosis who used cannabis heavily before getting sick had higher genetic risk for schizophrenia | Research

The takeaway

Patients who used cannabis weekly to daily before their first psychotic episode had significantly higher polygenic risk scores for schizophrenia, with the strongest effect in those who started before age 18.

Read this if you have a family history of schizophrenia or psychosis and want to understand how genetics and cannabis use interact.

Early heavy cannabis users had the highest schizophrenia genetic risk scores (Cohen's d = 0.42)

What the researchers found

Researchers assigned schizophrenia polygenic risk scores to 381 schizophrenia spectrum patients, 220 bipolar disorder spectrum patients, and 415 healthy controls. The polygenic risk score reflects how many common genetic variants associated with schizophrenia each person carries.

Patients who had used cannabis weekly to daily before their first illness episode had the highest genetic risk scores for schizophrenia, regardless of whether they were diagnosed with schizophrenia or bipolar disorder. The difference was statistically significant.

The effect was strongest among those who began heavy cannabis use before age 18. These early-onset frequent users had the largest difference in genetic risk compared to patients who never or rarely used cannabis, with a moderate effect size of 0.42.

Why it matters

This finding helps untangle the complex relationship between cannabis and psychosis. Rather than cannabis simply "causing" psychosis, the data suggest that individuals with higher genetic loading for schizophrenia may be more likely to use cannabis heavily before becoming ill. This does not rule out cannabis as an additional environmental trigger, but it suggests the relationship involves both genetic vulnerability and cannabis exposure.

The numbers in context

381 schizophrenia spectrum patients, 220 bipolar spectrum patients, 415 healthy controls. Weekly-to-daily cannabis users before illness had highest polygenic risk scores (p = 0.02, Cohen's d = 0.33). Early-onset frequent users (before age 18) versus non-users: p = 0.003, Cohen's d = 0.42. Reference sample for risk scores: 81,535 participants from PGC.

How the study worked

This was an observational genetic study using polygenic risk scores calculated from the Psychiatric Genomics Consortium schizophrenia case-control study (N = 81,535). An independent sample of 381 schizophrenia spectrum cases, 220 bipolar spectrum cases, and 415 healthy controls was genotyped and scored. Cannabis use history before illness onset was collected and participants were grouped by frequency of use.

What this study cannot tell us

The study cannot determine causality or direction of effect. It is possible that the same genes that increase schizophrenia risk also increase cannabis use propensity. Cannabis use history was based on retrospective self-report, which may be inaccurate. The study focused on common genetic variants and did not account for rare mutations or environmental factors beyond cannabis.

How to read the evidence

This is a well-powered genetic study with a large reference sample, but the observational design limits causal conclusions.

When this study was published

Published in 2018, using genetic data from the Psychiatric Genomics Consortium.

The bigger picture

This study contributes to the gene-environment interaction model of psychosis. It suggests that the link between cannabis and psychosis is not a simple one-way street but involves a complex interplay where genetic vulnerability both increases psychosis risk and may increase the likelihood of heavy cannabis use. Understanding this interaction is crucial for identifying who is truly at risk.

Questions still open

Do the same genetic variants that increase schizophrenia risk also drive cannabis-seeking behavior? Could polygenic risk scores eventually be used to identify individuals who should avoid cannabis? Does cannabis use in genetically high-risk individuals accelerate illness onset rather than cause it?

Common questions

Does this mean cannabis use is genetic?

Not exactly. The study found that people who developed psychosis and had used cannabis heavily before getting sick tended to carry more genetic variants associated with schizophrenia. This could mean genetic vulnerability increases both psychosis risk and the tendency toward heavy cannabis use.

Can genetic testing predict who should avoid cannabis?

Not yet with clinical reliability. Polygenic risk scores capture statistical tendencies across populations, but they are not precise enough to make individual predictions. Research in this area is ongoing.

Read the original research

Psychotic patients who used cannabis frequently before illness onset have higher genetic predisposition to schizophrenia than those who did not.

Psychological medicine, 48(1), 43-49

View on PubMed ↗Publisher’s paper ↗

Citation

Aas, M; Melle, I; Bettella, F; Djurovic, S; Le Hellard, S; Bjella, T; Ringen, P A; Lagerberg, T V; Smeland, O B; Agartz, I; Andreassen, O A; Tesli, M. (2018). Psychotic patients who used cannabis frequently before illness onset have higher genetic predisposition to schizophrenia than those who did not.. Psychological medicine, 48(1), 43-49. https://doi.org/10.1017/S0033291717001209