may not be informative for substance dependence that involves nicotine dependence alone or in combination with other substance dependence. rs1799971 is not significantly associated with nicotine dependence in some population based (20, 57) or treatment seeking smoker (28) samples. With respect to smoking related behaviors, the OPRM1 SNP rs1799971 minor allele (A) homozygote has been associated with an increased reinforcing value of nicotine in women and a tendency to prefer nicotine versus denicotinized cigarettes in both sexes (2), and with endorsing cigarette liking after negative mood induction (58). In a clinical trial studying the effects of transdermal nicotine and nicotine nasal spray, smokers with one or more copies of the major allele (G) were more likely to be abstinent and experienced less mood disturbance and short-term weight gain compared to smokers with two copies of the minor allele (59). The study also found that the genotype effect on treatment outcome was most pronounced in smokers receiving transdermal nicotine (59). Note however that the minor allele homozygote has been associated with increased long-term smoking cessation with the use of transdermal nicotine patch versus placebo (18).
