Genetic clues to the molecular basis of tobacco addiction and progress towards personalized therapy

The molecular processes that underlie addiction are beginning to unfold. Ge netically determined variations in dopaminergic neurotransmission predispos e to nicotine dependence In addition, tobacco use is likely to be governed by the rate at which smokers metabolize nicotine. Functional polymorphisms in cytochrome P450 monooxygenases that metabolize nicotine have now been de fined and it should soon be possible to identify fast nicotine metabolizers by DNA analysis. Here, we review the key neurotransmitter receptors and me tabolic enzymes implicated in tobacco dependence. We explore the potential benefits of classifying smokers according to the molecular aetiology of the ir habit. One major benefit will be in planning effective strategies for sm oking cessation. Methods of typing for alleles related to smoking behavior that might be suitable for use in clinical practice in the future will also be discussed.