Rivastigmine and Huperzine A as Treatments for Cocaine Dependence

The purpose of this study is to evaluate the interactions between cocaine and oral rivastigmine and between cocaine and oral huperzine A (HupA). The following Specific Aims are proposed: 1. Among cocaine-dependent, non-treatment seeking participants, to establish the ability of rivastigmine (3 or 6 mg, daily) or HupA (0.4 or 0.8 mg, daily), as compared to placebo, to reduce cocaine-induced craving (0, 20, and 40 mg, IV) and to reduce reinforcing effects produced by cocaine (20 mg, IV/infusion). Hypothesis. Relative to placebo-treated participants, treatment with rivastigmine or HupA will reduce cocaine-induced craving and choices for cocaine. 2\. To determine the safety of rivastigmine and HupA in cocaine-dependent participants who receive cocaine in a laboratory setting. Hypothesis 2A. Relative to placebo-treated participants, treatment with rivastigmine or HupA will not increase the adverse events produced by cocaine. Hypothesis 2B. Relative to placebo-treated participants, treatment with rivastigmine or HupA will reduce cocaine-induced increases in heart rate and blood pressure. 3\. To determine the effects of AChE inhibition on plasma levels of cocaine and cocaine metabolites. Hypothesis 3A. Relative to placebo-treated participants, treatment with rivastigmine, but not HupA, will be associated with increased plasma levels of cocaine. Hypothesis 3B. Relative to placebo-treated participants, treatment with rivastigmine, but not HupA, will be associated with increased formation of ecgonine and benzoylecgonine, and decreased formation of ecgonine methylester. 4\. a) provide a more frequent measure of heart rate (15 sec vs. 5 minutes) and b) measure a new dependent variable, physical activity, on days with and without cocaine exposure. Public Health Significance: Cocaine abuse is an important health problem that is associated with serious medical, psychiatric, social, and economic consequences. No medications are currently available for prevention of relapse in patients who are addicted to cocaine, and compounds such as rivastigmine and HupA are predicted to be useful for this indication. The testing of HupA is particularly exciting since it has antioxidant and neuroprotective properties that may also contribute to its efficacy as a treatment medication for cocaine dependence.