The Impact of Genetic Variation in CYP2D6 on the Pharmacokinetics and Pharmacodynamics of Methamphetamine

Methamphetamine abuse and addiction are widespread and is causing increasing pressures on social, public health and criminal justice systems worldwide. Some of the risk for developing addiction may be genetic. Identifying specific genotypes and understanding their interactions with the environment may help predict who is at risk for developing a disease. In this study the investigators are evaluating the contribution of differences in one genotype - called CYP2D6 to the removal of methamphetamine from the body. Methamphetamine is removed from the body by special enzymes in the liver. One of these enzymes is called Cytochrome P450 2D6. The activity of 2D6 is genetically determined. Some people have no active 2D6 whereas in others 2D6 is very active. One group of scientists found that people with low 2D6 activity were less likely to become methamphetamine addicts. In this study the investigators will determine the activity of your 2D6 by looking at the CYP2D6 genotype. If low levels of 2D6 decrease the risk of methamphetamine addiction it may be because there is less of the chemicals (called metabolites) made by 2D6. The first step in the metabolism (the process of removal of drugs from the body) of methamphetamine by 2D6 is conversion of methamphetamine to amphetamine and para-hydroxymethamphetamine. 2D6 then converts these to inactive chemicals. In addition to determining your genotype, the investigators are interested in the relationship of genotype with the methamphetamine metabolism. Thus, as part of this study, you will be given a modest oral dose of 5 milligrams of methamphetamine. After receiving the methamphetamine you will need to collect your urine for 24 hours. The purpose of this study is to investigate the impact of genetic variation in CYP2D6 on the disposition of methamphetamine in the human body as well as its pharmacologic effects to humans.