Genetic mediation of the link between schizophrenia and cannabis use

Cannabis use is likely to increase the risk for schizophrenia, but it is neither a necessary nor a sufficient cause. Genetic factors may mediate the link between cannabis and schizophrenia. Research has recently started to explore interactions and correlations between genes, cannabis, and psychosis. Results from studies using indirect measures of genetic liability to psychotic disorder suggest that the psychotogenic effect of cannabis is greater in individuals with a predisposition for psychosis than in those without such a predisposition (gene–environment interaction) and that predisposition for psychosis is correlated with cannabis use (gene–environment correlation). The few studies that have investigated genetic polymorphisms directly found no evidence of correlation between cannabis use and genetic characteristics, and are inconclusive with regard to gene–environment interaction. One study reported an interaction effect between cannabis use and the Val158MET polymorphism of the catechol-O-methyltransferase (COMT) gene on the development of schizophrenia, another study did not replicate these findings, and yet another found this interaction only in individuals who already had a high predisposition for psychosis but not in those with no predisposition for psychosis. Thus, although it is likely that interactions between genes and cannabis influence the development of schizophrenia, further work is necessary to identify which genetic variations are involved and how these interact with cannabis. The inclusion of higher-order gene–gene and gene–environment interactions may be needed to understand the complex relationship between cannabis and schizophrenia.