Genetic dissection of the psychotomimetic effects of cannabinoid exposure

• Cannabis use is an established risk factor for the development of schizophrenia.
• Genetic predisposition may moderate the psychosis-inducing effects of cannabis.
• Dopamine signalling genes (COMT, AKT1) modulate the cannabis-psychosis association.

Cannabis use is an established risk factor for the development of schizophrenia and related psychotic disorders. Factors that may mediate susceptibility to the psychosis-inducing effects of cannabis include the age at onset of first cannabis use, genetic predisposition, as well as interaction with other environmental risk variables. Clinical and preclinical genetic studies provide increasing evidence that, in particular, genes encoding proteins implicated in dopamine signalling are implicated in the cannabis–psychosis association. In the present review, we focus on both human and animal studies which have focused on identifying the neuronal basis of these interactions. We conclude that further studies are required to provide greater mechanistic insight into the long-term and neurodevelopmental effects of cannabis use, with implications for improved understanding of the cannabis–psychosis relationship.