The purpose of this study is to determine the safety of intravenous cocaine in subjects receiving oral donepezil.

This is a randomized, double-blind, double-dummy, placebo controlled, inpatient, single-center, parallel group evaluation of the potential for oral donepezil to attenuate cocaine-induced craving. Non-treatment-seeking cocaine-experienced volunteers will receive baseline treatment with intravenous cocaine (30Mg). Forty-two subjects that tolerate baseline cocaine infusions will then receive two subsequent intravenous doses of cocaine during double-blind treatment with oral placebo or 5 mg daily of donepezil. Each dose of cocaine will be preceded or followed by administration of intravenous placebo (saline) in a random order.

Inclusion Criteria:

• Non-treatment seeking, experienced cocaine users, who have used cocaine by smoking or intravenous injection within the four weeks prior to screening, and must supply a cocaine-positive urine obtained within four weeks of entry into the study.

Exclusion Criteria:

• Shows signs of psychostimulant toxicity, or has a history of a medical adverse reaction to cocaine or other psychostimulants, including loss of consciousness, chest pain, cardiac ischemia, or seizure.
• Has a current psychiatric disorder other than drug abuse or dependence or dementia.
• Meets the Diagnostic and Statistical Manual of Mental Disorders-IV criteria for dependence to opiates, benzodiazepines, alcohol, or other sedative-hypnotics.
• Has received opiate-substitution therapy (methadone or buprenorphine) within two months prior to enrollment.
• Has current or past history of seizure disorder, including alcohol- or psychostimulant- related seizures, or family history of seizure disorder.
• Has a diagnosis of adult asthma, or chronic obstructive pulmonary disease, including a history of acute asthma within the past two years, and those with current or recent (with the past two years) treatment with an inhaled or oral beta-adrenergic agonist.
• Has had head trauma that resulted in neurological sequelae.
• Has an unstable medical condition, which, in the judgement of investigators, would make participation hazardous.

All participating subjects