Childhood adversity and cannabis use are both known risk factors for psychosis. This study examined whether cannabis use might explain the link between childhood adversity and psychotic disorders. Data from 881 first-episode psychosis patients and 1231 controls from the EU-GEI study showed that household discord was associated with psychosis partly through cannabis use. Lifetime cannabis use mediated 17% of the association, cannabis potency mediated 14%, and frequency of use mediated 29%. Similar results appeared for early exposure to household discord. The findings suggest that harmful cannabis use patterns partially explain how household discord leads to psychosis, and children exposed to challenging home environments could benefit from interventions to prevent cannabis misuse.
Genetic risk for schizophrenia and cannabis use each contribute to specific symptom patterns across psychotic disorders, not just diagnostic categories. Among 617 first-episode psychosis patients, higher schizophrenia polygenic risk scores were linked to more severe negative and positive symptoms, regardless of diagnosis. In 979 controls, the same genetic risk was associated with all dimensions of psychotic experiences. Daily or current cannabis use was tied to more positive symptoms in both patients and controls, beyond the effect of genetic risk. The findings support a dimensional view of psychosis, where genetic liability relates to symptom severity and cannabis use specifically increases positive symptoms.
A specific genetic variation in the endocannabinoid system interacts with cannabis use to sharply increase the risk of a first episode of psychosis. Carrying two copies of the T allele of the FAAH rs2295633 gene variant, combined with cannabis use, made the probability of a first psychotic episode ten times higher compared to cannabis users without that genotype. No such increased risk appeared in non-users. The study also found that carriers of this genotype who used cannabis were more often treated with high-potency antipsychotics. The findings are preliminary and need replication.