Whether or not CD is included, substance abuse and/or dependence have been reported to be associated with CNR1 in some (Comings et al 1997; Ponce et al 2003; Schmidt et al 2002; Zhang et al 2004), but not all studies (Covault et al 2001; Heller et al 2001; Herman et al 2006; Li et al 2000). There are several potential explanations for these results. First, the inconsistent findings may result in part from a lack of phenotypic comparability across different studies. Substance dependence (SD) is a complex phenotype, which includes CD, OD, MD, AD, and others. This phenotypic heterogeneity could lead to different results. Second, inconsistent findings in relation to the association of CNR1 and substance use disorders may also result from differences in the populations studied, as well as from population stratification and admixture effects. Most previous studies based population membership on self-report, which may not be adequate to exclude potential population stratification effects. Third, some of the differences could derive from the use of different marker sets and analytic models. Finally, the inconsistent findings could have resulted from small sample sizes leading to inadequate statistical power in some studies.
