This study investigated whether FAAH C385A variance was associated with craving, withdrawal, and sensitivity to the acute effects of marijuana. From the intermediate phenotype perspective, each of these more narrowly defined phenotypes is influenced by CB1-regulated changes in mesocorticolimbic dopamine transmission, and CB1 binding by anandamide is affected by changes in FAAH efficacy. Frequent marijuana users homozygous for the C allele, were predicted to report more severe withdrawal symptoms after marijuana abstinence, greater craving after abstinence, and after exposure to a marijuana-related cue, and more positive and fewer negative reactions to the acute effects of marijuana than frequent users with at least one copy of the A allele. Additionally, C/C individuals were predicted to demonstrate greater HR increases after smoking marijuana than A/C and A/A individuals.
