Rivastigmine and Huperzine A as Treatments for Cocaine Dependence
Condition: Cocaine Dependence; Cocaine Addiction; Cocaine Abuse; Substance Abuse
MeSH terms: Substance-Related Disorders; Cocaine-Related Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine the safety and effects of rivastigmine and
      huperzine A (HupA), potential treatments for cocaine abuse, when used before experimental
      administration of cocaine, on a number of physical and psychological measures.
    

Detailed description: 
      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.
    

Intervention name(s): Placebo; Rivastigmine 3 mg; Huperzine A 0.4 mg; Rivastigmine 6 mg; Huperzine A 0.8 mg
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): The placebo groups will receive the same dosage throughout the study.; The 3 mg rivastigmine group will receive 3 mg rivastigmine only in the evening of Day 1, 3 mg in the morning and 0 mg in the evening of Days 2-9, and 3 mg in the morning of Day 10.; The 0.4 mg HupA group will receive 0.2 mg HupA only in the evening of Day 1, 0.2 mg in the morning and evening of Days 2-9, and 0.2 mg in the morning of day 10.; The 6 mg rivastigmine group will receive 3 mg rivastigmine only in the evening of Day 1, 3 mg in the morning and 0 mg in the evening of Days 2-5, 3 mg in the morning and evening of Days 6-9, and 3 mg in the morning of Day 10.; The 0.8 mg HupA group will receive 0.2 mg HupA only in the evening of Day 1, 0.2 mg in the morning and evening of Days 2-5, 0.4 mg in the morning and evening of Days 6-9, and 0.4 mg in the morning of Day 10.
Other intervention name(s): Sugar pill; Exelon; Huperzine; Exelon; Huperzine
Intervention MeSH terms: Rivastigmine; Huperzine A
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Keywords: Cocaine; Rivastigmine; Huperzine A