The primary objective of this study is to conduct a preliminary assessment of the possible efficacy of ondansetron to reduce methamphetamine use in outpatients with methamphetamine dependence. The hypothesis is that ondansetron treatment compared to placebo will decrease the weekly proportion of methamphetamine positive urines. The results of this study will be used to design subsequent larger studies to confirm the efficacy of ondansetron. This study is also intended to gather preliminary information on biological or psychosocial characteristics of patients who may show better ondansetron treatment responsiveness.

This is a double-blind, placebo-controlled, parallel-group design study in which, after screening and a 2-week baseline assessment period, subjects will be equally randomly assigned to one of two treatment groups, tiagabine or matched placebo. All patients will receive manualguided cognitive behavioral therapy (CBT). Medication dosing will occur over 15 weeks with the first three weeks being dose escalation and the last three weeks being dose taper. Follow-up will consist of assessments once each week during weeks 13, 14, 15, and 19. Randomization strata include study site, gender and frequency of cocaine use in the 30 days prior to screening.