A further example of possible gene by environment interactions centers on the etiology of schizophreniform and related psychotic disorders, where cannabis use assumes the role of environmental exposure. Controversially, it has been proposed that adolescent cannabis use may increase risks of psychosis related disorders,98 although only a small percentage of those using cannabis develop psychosis. Longitudinal analyses suggest a possible explanation for this apparent contradiction: adolescent onset cannabis use was strongly associated (OR=10.9) with schizophreniform disorder among individuals characterized by the Val/ Val genotype of COMT while among individuals with one or two copies of the Met allele, adolescent onset cannabis use was not significantly associated with increased risks of schizophreniform disorder.99 While this broad pattern of findings was reported across multiple measures of “psychosis”, there have been no published replications in other general population samples. Nonetheless, parallel findings from cannabis challenge100 and experience sampling101 methodologies support the hypothesis that carriers of the Val/Val genotype may be particularly susceptible to the psychosis inducing effects of THC.
