There have been few studies looking at the rate of nicotine metabolism as a mediator of dependence during adolescence, and these studies have yielded conflicting results (13–17). Nicotine is metabolized primarily by the liver enzyme CYP2A6. When looking at the effects of nicotine metabolism on the development of addiction in adolescent smokers, O’Loughlin and colleagues (14) reported that adolescents with CYP2A6 alleles associated with slower metabolism of nicotine were at increased risk of becoming nicotine dependent. In contrast, Audrain-McGovern and colleagues (13) found that adolescents with a genetic profile consistent with normal nicotine metabolism (wild type CYP2A6) progressed to nicotine dependence (defined by the mFTQ) more quickly than slower metabolizers.
