Candidate medications for smoking cessation may be screened more efficiently if initial evaluations in humans combine the practical advantages of laboratory studies with the clinical validity of clinical trials, such as by increasing participants' "quit motivation" during brief testing. We manipulated "intrinsic" quit motivation by recruiting smokers who either did intend to quit soon ("treatment seekers," N = 47) or did not ("nonseekers," N = 93), and "extrinsic" quit motivation by providing or not providing reinforcement for abstinence ($12/day). All the subjects smoked as they would usually do during weeks 1 and 3, and tried to quit during weeks 2 and 4 using either a nicotine patch (21 mg) or a placebo patch, in accordance with the crossover design of the study. The nicotine patch increased abstinence in treatment seekers but not in nonseekers. Reinforcement had a main effect on abstinence but did not moderate the effects of the nicotine patch or treatment-seeking status. Intrinsic, but not extrinsic, quit motivation of participants may enhance the validity of brief tests of medication efficacy for smoking cessation.

Genes coding for nicotinic acetylcholine receptors may influence response to nicotine replacement therapy for smoking cessation. We examined the association of a 3′ untranslated region polymorphism (rs2072661) in the nicotinic acetylcholine receptor β2 subunit (CHRNB2) gene with quitting success in response to nicotine versus placebo patch during a short-term test of patch effects. In a within-subjects cross-over design, smokers of European descent (n = 156) received 21 mg nicotine and placebo patch in counter-balanced order, during two separate 5-day simulated quit attempts, each preceded by a week of ad libitum smoking. Abstinence was assessed daily by CO < 5 ppm. Smokers with the CHRNB2 GG genotype had more days of abstinence during the nicotine versus placebo patch week compared with those with the AG or AA genotypes (P < 0.01). Moreover, nicotine patch increased the probability of quitting on the target quit day, quitting anytime during the patch week, and avoiding relapse among those with the GG genotype but not the AA/AG genotypes, although the nicotine × genotype interaction was significant only for quitting on the target quit day (P < 0.05). Regardless of patch condition, quitting on the target quit day was more likely in those with the GG genotype versus AA/AG genotypes (P < 0.05). Genetic associations were not observed for craving or withdrawal responses to nicotine versus placebo patch. These findings are consistent with previous evidence of association of this variant with smoking cessation and suggest that polymorphisms in the nicotinic acetylcholine receptor β2 subunit gene may influence therapeutic responsiveness to cessation medications. (Cancer Epidemiol Biomarkers Prev 2009; 18(10):2608-12)

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