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Recent evidence documents that cannabis use by young people is a modest statistical risk factor for psychotic symptoms in adulthood, such as hallucinations and delusions, as well as clinically significant schizophrenia. The vast majority of cannabis users do not develop psychosis, however, prompting us to hypothesize that some people are genetically vulnerable to the deleterious effects of cannabis.

In a longitudinal study of a representative birth cohort followed to adulthood, we tested why cannabis use is associated with the emergence of psychosis in a minority of users, but not in others.

A functional polymorphism in the catechol-O-methyltransferase (COMT) gene moderated the influence of adolescent cannabis use on developing adult psychosis. Carriers of the COMT valine¹⁵⁸ allele were most likely to exhibit psychotic symptoms and to develop schizophreniform …