At the behavioral and clinical levels, data were analyzed from a new study and a previously published study of moderate to heavy non–treatment-seeking drinkers. In both studies, individuals with the CT genotype reported greater reward than those with the TT genotype when consuming alcohol. Specifically, individuals with the CT genotype seem to enjoy drinking alcohol more than those with the TT genotype. In addition, consistent with the neuroimaging results, there was a significant interaction with a medication that targets mesocorticolimbic neurocircuitry. These findings are also consistent with the animal studies that manipulated CB1 function and found that the CB1 receptor forms a critical link between alcohol and dopamine release in mesocorticolimbic structures. Thus, it seems that the CB1 receptor and the polymorphisms that alter the regulation of this receptor may affect the effects of alcohol on the mesocorticolimbic structures that underlie drugseeking behavior.5–17 The implication is that incentive salience may increase more rapidly with repeated exposure to alcohol in individuals with the CT genotype such that those with high levels of exposure might be expected to demonstrate greater levels of cue-elicited craving and might benefit from medications that target this neuronal circuitry.
