Research has focused on identifying specific genetic influences on the ability to quit smoking. Such research can identify novel molecular targets for medication development. Further, pharmacogenomics research focused on genetic influences on quitting success with specific medications could potentially lead to the development of targeted therapy approaches that are more efficacious. This review focuses on the role in smoking cessation of genes coding for neuronal nicotinic acetylcholine receptors (nAChRs) and nicotine metabolizing enzymes, the initial molecular targets for nicotine’s effects. First, we provide a brief overview of the neurobiology of nicotine’s effects in the brain, phenotyping of smoking cessation behaviors, and approaches for genetic studies. Next, we review the biological plausibility and available evidence for the association of specific cholinergic genes with smoking cessation and therapeutic response. Lastly, we review nicotine pharmacokinetics and the role of genetic variability in nicotine metabolism enzymes.
