Withdrawal symptoms interfere with smoking cessation (Shiffman et al. 2006) and faster metabolizers of nicotine may experience more intense withdrawal symptoms due to a more rapid decline in blood and brain nicotine concentrations after smoking a cigarette. In adolescent light smokers, faster metabolizers reported greater withdrawal symptoms after 24 h and described themselves as more highly addicted than slow metabolizers (Rubinstein et al. 2008). In adult treatment-seeking smokers, higher nicotine metabolite ratios predicted more severe cravings for cigarettes after 1 week of treatment with transdermal nicotine (Lerman et al. 2006); however, there was no significant association of the nicotine metabolite ratio with withdrawal symptoms or nicotine craving in a second study of transdermal nicotine (Schnoll et al. 2009) or in the bupropion placebo-controlled trial (Patterson et al. 2008). It is possible that differences in very early withdrawal symptoms exist, but were not captured by the measurement points used in the clinical trials.
