Pramipexole as a Treatment for Cocaine Dependence

In this protocol we propose to assess the impact of treatment with higher doses of the
potent D2/3 agonist pramipexole, using the extended release preparation that has been shown
to produce continuous DA receptor stimulation. Pramipexole is a non-ergot DA 3
receptor-preferring agonist. In contrast to pergolide, bromocriptine and cabergoline, it
does not stimulate 5-HT2B receptors and therefore does not cause cardiac valvulopathy. It
can therefore be safely used chronically at higher doses, whereas pergolide has been
withdrawn from the market for causing cardiac valvulopathy.

Inclusion Criteria:

- Be English-speaking volunteers who are not seeking treatment at the time of the
study. We require proficiency in English to ensure good communication with staff.

- Be aged between 18 and 55 years.

- Meet DSM-IV TR criteria for cocaine dependence.

- Have a self-reported history of using cocaine by the IV or smoked route.

- Have vital signs as follows: supine blood pressure > 100/65 mm Hg, a seated blood
pressure of > 90/60 mm Hg, and an orthostatic change < 20 mm Hg systolic or <10 mm Hg
diastolic on standing. To ensure that subjects will not be at risk from cocaine, the
resting pulse must be < 90 bpm and the blood pressure must be < 150 mmHg systolic and
< 90 mmHg diastolic.

- Have hematology and chemistry laboratory tests that are within reference limits
(±10%), with the following exceptions: (a) total bilirubin must be < 2x upper limit
of normal and ALT, AST, and alkaline phosphatase <3× the upper limit of normal and
(b) kidney function tests (creatinine and BUN) within normal limits.

- Have a baseline ECG that demonstrates clinically normal sinus rhythm, clinically
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 seizure disorder or brain injury.

- Have any previous medically adverse reaction to cocaine, 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 that would require ongoing
treatment or that would make study compliance difficult; and history of suicide
attempts within the past year and/or current suicidal ideation/plan.

- 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 or are taking antiretroviral medication.

- Be pregnant or nursing. Females must provide negative pregnancy urine tests upon
hospital admission and at the end of study participation. Females must either be
unable to conceive (i.e., surgically sterilized, sterile, or postmenopausal) or be
using a reliable form of contraception (e.g., abstinence, birth control pills,
intrauterine device, or condoms with spermicide).

- Have asthma or currently use theophylline or other sympathomimetics.

- Have any other illness, condition, or use of psychotropic medications, which in the
opinion of the PI and/or the admitting physician would preclude safe and/or
successful completion of the study.