CVT-10216, an isoflavone compound, is a novel, highly potent and selective, reversible inhibitor of aldehyde dehydrogenase 2 (ALDH2) with IC50s of 29 and 1300 nM for ALDH2 and ALDH1, respectively. CVT-10216 increases acetaldehyde after alcohol gavage and inhibits 2-bottle choice alcohol intake in heavy drinking rodents, including deprivation-induced drinking. Moreover, CVT-10216 also prevents operant self-administration and eliminates cue-induced reinstatement of alcohol seeking even when alcohol is not available (i.e., no acetaldehyde). Alcohol stimulates DA release in the NAc, which is thought to contribute to increased drinking and relapse in alcoholism. CVT-10216 prevents alcohol-induced increases in NAc DA without changing basal levels.