Cannabis use disorders are multifactorial and these factors (genes and environment) interact to shape its development [139]. Therefore, careful attention to the mechanisms by which changes in the environment modify genetic risk is required. To date, all gene-environment interaction studies of cannabis have treated cannabis use as the environmental exposure. For example, Caspi et al found that early exposure to cannabis use modified the genetic effects of COMT (catecholamine-o-methyl transferase) on psychosis [140]. There has been a recent failure to replicate this result in a large UK case-control study by Zammit and others [141]. The genetic influences on cannabis use disorders itself may also be modified by environmental stimuli, such as early childhood adversity or stressful life events.
