The investigation of genetic factors that influence the development and expression of drug-related problems is one of the most promising areas of research on addiction. With respect to the heritability of illicit drug use, and in particular cannabis use, recent studies have documented that genetic factors account for a significant portion of variance in use, abuse and dependence [1–7]. In an effort to identify genetic factors and the mechanisms by which they influence addiction, the utilization of an intermediate phenotype or ‘endophenotype’ approach may be useful. The ideal intermediate phenotype, or ‘endophenotype,’ would be one that is narrowly defined, associated with the clinical manifestation of addiction, and related to an underlying biological mechanism [8]. Importantly, the use of narrowly defined phenotypes increases the statistical power available to detect significant associations with particular candidate genes and facilitates the interpretation of the findings. While recent work on alcohol and drug abuse has moved in this direction, cannabis research has yet to follow because of the lack of cannabis dependence endophenotypes.
