The role of pharmacogenetically-variable cytochrome P450 enzymes in drug abuse and dependence

The risk of drug dependence is determined by the interaction of drug, individual and environment. 'Pharmacogenetics' is the study of the influence of heredity on the response to drugs and their fate in the body; these studies aim to improve the understanding of inter-individual variability in drug response. The authors have applied this research approach to the study of drug metabolism and dependence. Specifically the interaction of genetically variable hepatic cytochrome P450 (CYP) enzymes and their effect on self-administration of drugs has been examined. Many drugs of abuse are substrates (e.g., amphetamines, codeine, nicotine) or inhibitors (e.g., (-)-cocaine) of polymorphic CYPs. Drug metabolism by genetically polymorphic enzymes can have significant clinical implications relating to drug toxicity, therapeutic failure, drug-drug interactions, disease susceptibility and abuse liability. There is good evidence that drug metabolism by genetically variable CYPs can influence the risk of drug dependence, the amount of drug consumed by dependent individuals and some of the toxicities associated with drug-taking behavior. It is anticipated that pharmacogenetics will be used to identify individuals at a greater risk for specific drug dependencies, provide information that can lead to novel treatment and prevention approaches as well as provide guidance for individualization of treatment choice.