This application seeks continued support to replace and to extend the existing Medication Development Unit for Stimulant Abuse (P50 DA 12755). The thematic emphasis that unifies this continuation of the Center is the development of pharmacological treatments for stimulant abuse through comprehensive and efficient methodologies applied by a multidisciplinary team. The P50 project activities aligned with this theme will involve an ever greater linkage of Phase I with Phase II work, an even stronger effort to apply advanced biostatistical methods to isolate effects of missing data and to identify potential medication effects in subgroups, a more concerted effort to develop biomarkers that discriminate meaningful differences in outcomes, and a more focused approach to the evaluation of medications within the context of carefully specified and timed behavioral interventions. This P50 Center continuation proposes a Core for conducting Administrative and Scientific Integration and Phase I and Phase II research projects that will complete the development of four medications for methamphetamine abuse from initial stages of safety/interaction through preliminary efficacy trials. The Specific Aims of this coordinated research activity are: (1) to identify and test novel medications for the treatment of stimulant abuse and dependence; (2) to conduct Phase I and Phase II trials of approved medications and novel compounds with potential for the treatment of stimulant-related disorders, in the context of concurrent behavioral treatments; and (3) to improve the efficiency of conducting medications research by using best practices and by applying cutting-edge biostatistical methods when analyzing trials data, creating a resource available to the field as a center of excellence in the area of clinical trials for stimulant abuse and dependence. The activities of the Core and two research projects in this application are designed to reflect innovation and multidisciplinary effort to maximize the likelihood of finding breakthroughs in the pharmacological treatment of stimulant abuse that can be brought into practice.