It appears likely that if cannabis exposure activates diathesis to psychosis (via COMT) then this effect is limited to individuals with additional vulnerabilities (e.g. psychosis proneness) or adverse exposures (e.g. childhood abuse). Alternatively, it is also possible that overlapping genetic (and environmental) factors link cannabis use and psychosis. However, gene association studies with COMT, as well as other dopaminergic (e.g. DRD2), cannabinoid (e.g. CNR1) and cholinergic (e.g. CHRNA7) polymorphisms have failed to show consistent associations with cannabis use and psychosis (71). Overall, the small sample size of a number of these studies limits their generalizability and meta-analysis across studies is needed. Adequately powered samples of psychotic disorders (e.g. Schizophrenia and Bipolar Disorder in the Psychiatric Genomics Consortium) with genomewide association data (72) might provide the most promising search for all variants whose influence on psychosis is moderated by early cannabis exposure.
