The goal of this study was to determine the influence of the COMT Val158Met polymorphism on nicotine responses in smokers. The outcomes examined were those predicted to be likely modulated by the COMT enzyme, including measures of cognitive performance, withdrawal severity, subjective drug effects, and cardiovascular responses to nicotine (18–21). To assess the outcomes of interest, we used an IV nicotine administration procedure. In contrast to other slower nicotine delivery systems, IV nicotine administration produces rewarding effects in male and female smokers (22). Based on the known biological effects of the COMT Val158Met variant, we hypothesized that smokers who carry two copies of the Val allele would experience less rewarding effects from nicotine, perform worse on selected cognitive tasks, and experience more severe withdrawal symptoms compared with those who carry the Met allele.
