This cross-sectional study of 109,308 UK Biobank participants investigated the relationship between cannabis use, schizophrenia polygenic risk, and four types of psychotic experiences (auditory and visual hallucinations, persecutory and delusions of reference). A strong, dose-dependent relationship was found between cannabis use and all four psychotic experiences, particularly persecutory delusions. Cannabis users experienced earlier-onset, more distressing psychotic experiences, but not necessarily increased help-seeking. Individuals with high schizophrenia polygenic risk scores showed stronger associations between cannabis use and psychotic experiences, suggesting increased vulnerability to cannabis-induced psychosis in genetically predisposed individuals. The study highlights the utility of biobanks in understanding gene-environment interactions and the potential for personalized harm reduction interventions.

Michael Wainberg, Grace R. Jacobs, Marta di Forti, Shreejoy J. Tripathy