DESCRIPTION (provided by applicant): This four-year study will evaluate the efficacy of treatment with methylphenidate compared to placebo in the context of behavioral therapy for methamphetamine use disorders (abuse or dependence) in a population of 90 adults seeking treatment at the UCLA ISAP Outpatient Clinical Research Center. The project will employ an experimental design involving ramping from two dosage levels of methylphenidate (MPH; 18mg/day for one week, and 36mg/day for one week) to the hypothesized active dosage (54mg/week for 8 weeks). After satisfying all inclusion/exclusion requirements, participants will be enrolled into the study for an initial two weeks for reinforcement of clinic attendance and collection of urine samples--during the first two-week screening period, only attendance is incentivized, with no contingency on results of thrice-weekly urine tests. The motivational incentives component continues throughout the study, with fixed compensation for attendance during the medication phase, in conjunction with escalating opportunities of increased reward for two or more consecutive drug-free urine samples (post run-in). Equal numbers of subjects will be assigned to either placebo or medication to maintain a balanced design, resulting in 45 subjects per condition. Aims of the study are: Aim 1. To evaluate the ability of sustained-release MPH (54mg once daily for 8 weeks) to reduce stimulant abuse and increase retention in the protocol among a sample of adults seeking treatment for MA use disorders. Aim 2. To examine the clinical utility of sustained-release MPH as a pharmacotherapy for methamphetamine use disorders. Aim 3. To assess functioning of participants in terms of psychiatric, cognitive, social, and physical domains. There is a critical need for systematic evaluation of strategies for treating methamphetamine use disorders. Thus, this project addresses NIDA's goal of developing an effective pharmacotherapy for stimulant use disorders, which constitute a considerable public health problem with severe consequences to social service systems, the criminal justice system, and to millions of individuals and families. PUBLIC HEALTH RELEVANCE: The proposed research is of considerable public health significance in that it will provide foundational information on a potential medication-based treatment for methamphetamine dependence, a serious drug problem with extensive impacts. If proven effective, the protocol could be useful in reducing drug-related consequences such as criminal activity, social disruption, and elevated risk of HIV transmission/infection due to increased frequency of unsafe sexual activities while on methamphetamine. A combination of treatment approaches may be most effective, and the proposed project will assess the utility of MPH in combination with proven behavioral therapy.