Methamphetamine abuse and dependence have for some time been significant issues in other parts of the world, including several southeast Asian countries, and have now become one of the most significant substance abuse problems in the United States, gaining recent national attention in Congressional hearings and network news programs. Modafinil is a non-amphetamine type stimulant that acts as a wakefulness-promoting drug, and is approved for managing symptoms of narcolepsy (i.e., daytime somnolence). Its precise mechanism of action in promoting wakefulness remains unclear, but it is pharmacologically distinct from stimulants that are sympathetic amines (Ferraro et al 1999; Jasinski 2000; Mignot et al 1994; Saper and Scammell 2004; Walsh et al 2004). Modafinil is a medication warranting evaluation as a treatment for MA dependence. It has a half-life of approximately 15 hours and reaches steady state in 2-4 days (Package insert) and will likely require once daily dosing, which reduces problems with medication adherence.

This application proposes a placebo-controlled double-blind trial of modafinil, on a platform of contingency management (CM) and individual cognitive-behavioral (CBT) counseling, for the treatment of methamphetamine dependence.

Participants in this study will complete a 2-week baseline screening period during which they will provide urine samples and complete physical and psychological assessments to establish their eligibility for the study. In addition, participants will be asked to provide a blood or saliva specimen for genetic testing in order to identify genetic variations that influence response to methamphetamine and to treatment with modafinil. If participants agree, genetic specimens will also be stored at UCLA and may be used in future studies to examine additional genes and/or shared with other investigators. Upon successful completion of this period, participants will be randomly assigned to receive either modafinil (400mg qd) or placebo during the 12 weeks of the study. Neither the participants nor study staff will know who is receiving active medication or placebo. Regardless of medication condition, all participants will receive CM and weekly individual CBT counseling sessions to help them stop using methamphetamine and prevent relapse. They will attend the clinical research site (either at the UCLA Hollywood Clinic, or the Rancho Cucamonga site) three times per week, providing urine samples at each visit, completing data measures, and receiving individual CBT counseling on one visit each week. At the end of the 12-week study, the medication or placebo will be discontinued. Participants will return to the research site approximately 30 days following medication discontinuation for a brief health check to assess any possible lingering side effects and complete brief data measures.