Use of Donepezil for Treatment of Cocaine Dependence

Phase 2

Completed

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

Detailed Description: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Oral Placebo First	Donepezil, 5 mg daily	Three days of daily treatment with oral placebo, followed by three days of daily treatment with 5 mg of donepezil
Oral Placebo First	Oral Placebo	Three days of daily treatment with oral placebo, followed by three days of daily treatment with 5 mg of donepezil
Donepezil First	Donepezil, 5 mg daily	Three days of daily treatment with 5 mg of donepezil, followed by three days of daily treatment with oral placebo.
Donepezil First	Oral Placebo	Three days of daily treatment with 5 mg of donepezil, followed by three days of daily treatment with oral placebo.

Primary Outcome Measures

Name	Time	Method
Cocaine Safety in Subjects Receiving Donepezil	Two weeks	Patients evaluated for clinical and laboratory adverse events

Secondary Outcome Measures

Name	Time	Method
Cocaine Subjective Effects	3 to 30 minutes	Cocaine Induced 'High' by VAS (visual analogue scale, between 3 and 30 minutes after intravenous dosing, in mm). VAS results ranged from 0 (minimum effect) to 100 (maximum effect).
Cocaine Pharmacokinetics	0 to 8 hours	Area-Under-the-Curve for Plasma Concentration