The primary objective of this study is to conduct a preliminary assessment of the possible efficacy of ondansetron to reduce cocaine use in outpatients with cocaine dependence.  Hypotheses are that ondansetron will increase the weekly mean proportion of cocaine non-use days assessed by self report of use and confirmed by urine assays for BE, that the weekly proportion of BE positive urines will be decreased, and that the total number of cocaine-free urines will be increased in groups treated with ondansetron when compared to placebo controls.  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. In particular, biological measures reflecting individual differences in serotonergic function are included.

The primary objective of this study is to determine the safety of the selegiline concurrent with dmethamphetamine challenges of 15 mg and 30 mg i.v. The primary outcome measures are cardiovascular responses (HR, BP) to the i.v. methamphetamine challenges.

The primary objective of this study is to determine the safety of tolcapone treatment, compared to placebo treatment, concurrent with i.v. cocaine infusions of 20 and 40 mg, with the focus being on cardiovascular responses (HR, BP) to the i.v. cocaine infusions.