There are a few plausible mechanisms that may underlie associations of individual differences in nicotine metabolism with smoking cessation in the nicotine-patch condition (Lerman et al., 2006). There is some evidence that slower metabolizers may have lower levels of abstinence-induced cravings. Indeed, among the participants who had successfully stopped smoking after 1 week of nicotine-patch therapy, the metabolite ratio was significantly associated with the intensity of self-reported cravings, and these, in turn, predicted abstinence (Lerman et al., 2006). However, the most obvious explanation is that slower metabolizers obtain higher treatment levels of nicotine from the patch than higher metabolizers. Indeed, this was found in the trial (Lerman et al., 2006); however, treatment levels of plasma nicotine accounted for a very small proportion of the variance in quitting. Further, the presence of an association of nicotine metabolism with abstinence at 6-month follow-up, after treatment was discontinued, argues against differences in metabolism of nicotine from the patch being the only reason for the improved cessation rates. Thus, nicotine metabolism rate may influence quitting success independent of treatment, and this hypothesis was addressed in the placebo-controlled trial discussed below.
