With respect to the use of these variables as endophenotypes, the findings also provide some ‘proof of concept’ in the form of significant associations between these variables and putatively functional SNPs that have been associated previously with substance abuse. The findings indicate that a T to C SNP in the CNR1 gene is a significant predictor of withdrawal after abstinence, as well as a predictor of overall levels of craving. A previous study has suggested that individuals with the C substitution may have an alternative CNR1 transcript that is associated with a higher risk for developing substance abuse problems [36]. Consistent with this previous work, the present study indicates that individuals possessing one or more C alleles are more likely to experience greater withdrawal, negative affect and higher levels of craving to smoke more marijuana. In addition, CNR1 C-carriers had 20% higher marijuana dependency checklist scores and used 30% more joints per month as T/T subjects. Furthermore, the present study, consistent with a previous study linking the FAAH SNP with substance abuse [38], observed a significant association between this SNP
