Use of Donepezil for Treatment of Cocaine Dependence

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

Detailed Description
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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.

Official Title
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Donepezil Effects on Cocaine Craving and Pharmacokinetics

Conditions
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Cocaine Abuse and Dependence

Intervention / Treatment
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* Drug: Donepezil, 5 mg daily
* Other: Oral Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oral Placebo First<br>Three days of daily treatment with oral placebo, followed by three days of daily treatment with 5 mg of donepezil | Drug: Donepezil, 5 mg daily<br>* This is a commercially available cholinesterase inhibitor that is approved for use in Alzheimer's disease.<br>* Other names: Aricept;Other: Oral Placebo<br>* Inactive Comparator with Similar Appearance to Active Medication<br>* Other names: Inactive Comparator;|
| Experimental: Donepezil First<br>Three days of daily treatment with 5 mg of donepezil, followed by three days of daily treatment with oral placebo. | Drug: Donepezil, 5 mg daily<br>* This is a commercially available cholinesterase inhibitor that is approved for use in Alzheimer's disease.<br>* Other names: Aricept;Other: Oral Placebo<br>* Inactive Comparator with Similar Appearance to Active Medication<br>* Other names: Inactive Comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cocaine Safety in Subjects Receiving Donepezil | Patients evaluated for clinical and laboratory adverse events | Two weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cocaine Subjective Effects | 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). | 3 to 30 minutes | 
| Cocaine Pharmacokinetics | Area-Under-the-Curve for Plasma Concentration | 0 to 8 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acetylcholine, Acetylcholinesterase, Butyrylcholinesterase, Cholinesterase Inhibitor