The purpose of this study is to assess the efficacy of rivastigmine (Exelon), an acetylcholinesterase inhibitor and cognition-enhancer, which is approved for the treatment of dementia of the Alzheimer''''s type, in the treatment of methamphetamine dependence.

The study design will be a double-blind placebo-controlled safety/interaction study that will evaluate rivastigmine at two dose levels (at 1.5mg qd and 1.5mg bid versus placebo). This design was selected to provide for an assessment of the effects of rivastigmine, compared to placebo, on (1) the cardiovascular and subjective effects produced by methamphetamine, and (2) the reinforcing effects produced by methamphetamine.

Accepts Healthy Volunteers

Inclusion Criteria:

• Be English-speaking volunteers who are not seeking treatment at the time of the study
• Meet DSM IV TR criteria for methamphetamine abuse or dependence
• Have a self-reported history of using methamphetamine by the smoked or IV route
• Have vital signs as follows: resting pulse between 50 and 90 bpm, blood pressures between 85-150mm Hg systolic and 45-90mm Hg diastolic; this criterion must be met within 2 days of admission
• Have hematology and chemistry laboratory tests that are within normal (+/- 10%) limits with the following exceptions: a) liver function tests (total bilirubin, ALT, AST, and alkaline phosphatase) < 3 x the upper limit of normal, and b) kidney function tests (creatinine and BUN) < 2 x the upper limit of normal
• Have a baseline ECG that demonstrates normal sinus rhythm, normal conduction, and no clinically significant arrhythmias
• Have a medical history and brief physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the admitting physician and the principal investigator

Exclusion Criteria:

• Have any history or evidence suggestive of seizures or brain injury
• Have any previous medically adverse reaction to methamphetamine, including loss of consciousness, chest pain, or epileptic seizure
• Have neurological or psychiatric disorders, such as psychosis, bipolar illness or major depression as assessed by SCID; organic brain disease or dementia assessed by clinical interview;history of any psychiatric disorder which would require ongoing treatment or which would make study compliance difficult;history of suicide attempts within the past three months assessed by SCID and/or current suicidal ideation/plan as assessed by SCID
• Have evidence of clinically significant heart disease or hypertension, as determined by the PI
• Have a family history in first-degree relatives of early cardiovascular morbidity or mortality, as determined by the PI
• Have evidence of untreated or unstable medical illness including: neuroendocrine, autoimmune, renal, hepatic, or active infectious disease;
• Have HIV and are currently symptomatic, have a diagnosis of AIDS, or are receiving antiretroviral medication
• Currently pregnant or nursing. Other females must either be unable to conceive (i.e., surgically sterilized, sterile, or post-menopausal) or be using a reliable form of contraception (e.g., abstinence, birth control pills, intrauterine device, condoms, or spermicide). All females must provide negative pregnancy urine tests before study entry, upon hospital admission, and at the end of study participation
• Have any history of asthma, chronic coughing and wheezing, or other respiratory illnesses
• Currently use alpha or beta agonists, theophylline, or other sympathomimetics
• Have any other illness, condition, or use of medications, which in the opinion of the PI and/or the admitting physician would preclude safe and/or successful completion of the study