In our study, smokers with the Val/Val genotype, compared with Met carriers, reported higher ratings of mostly negative drug effects, including “Feel Anxious,” “Feel Bad Effects,” “Feel Sedated,” “Feel Down” and “Feel the Drug Strength.” In contrast, no genotype effects were observed for the ratings of items that reflect nicotine’s reinforcing properties including “Good Drug Effects,” “Like the Drug Effects” or “Want More Drug.” This genotype effect was primarily observed in response to nicotine, and not to saline, administration, suggesting a pharmacogenetic effect of the Val/Val genotype. COMT effects were observed for both 0.5 and 1.0mg/70 kg of nicotine dose. Previous studies have shown that COMT Val158Met variation moderates responses to non-drug rewards or aversive stimuli (19, 20); however, the influence of the COMT Val158Met polymorphisms on the rewarding or aversive drug effects has not been reported. For example, healthy controls with the Val/Val genotype report a decreased ability to experience reward in the routine of daily life and report less happiness compared with those with the Met/Met genotype (20). In a recent functional fMRI study healthy controls with the
