Effects of Aripiprazole on Cocaine Craving and Self-Administration

Study Overview
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Brief Summary
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The purpose of this study is to investigate whether aripiprazole will decrease cocaine self-administration, subjective effects and cravings compared to placebo.

Detailed Description
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Despite the recent increase in data about cocaine's basic neurochemical mechanisms of action, progress towards the development of an effective pharmacological treatment for cocaine abuse has been disappointing. We are proposing to use our laboratory model of repeated dose cocaine self-administration to assess the potential efficacy of the novel antipsychotic, aripiprazole. Aripiprazole is a partial agonist at both the dopamine D2 receptor and at the serotonin 5HT1a receptor, while antagonizing the 5HT2a receptor. By functioning as a partial D2 agonist, aripiprazole is hypothesized to function as a D2 antagonist during hypodopaminergic states, such as during cocaine use, while functioning as a D2 agonist during hypodopaminergic states, such as during cocaine withdrawal. This 42-day, outpatient/inpatient/outpatient/inpatient protocol will evaluate the effects of aripiprazole maintenance (0, 15 mg/day) on cocaine craving, subjective effects, and self-administration using a within-subjects design. Non-treatment seeking cocaine abusers will be maintained outpatient for 16 days of dose maintenance prior to inpatient cocaine self-administration sessions. During the inpatient phases, volunteers will live on a hospital clinical research unit and will participate in laboratory sessions in which they will have the opportunity to choose between repeated doses of smoked cocaine and $5. In addition to measuring their cocaine self-administration, we will measure the cardiovascular and subjective effects of cocaine under each aripiprazole maintenance condition.

Official Title
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Effects of Aripiprazole on Cocaine Craving and Self-Administration

Conditions
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Cocaine Abuse

Intervention / Treatment
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* Drug: Aripiprazole + Cocaine
* Drug: Placebo + Cocaine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets DSM-IV criteria for current cocaine abuse Average use of smoked cocaine is at least 2x/week for past 6 mos); currently spends at least $70 per week on cocaine Has patterns of smoked cocaine use in terms of frequency and amounts which parallel or exceed those administered in the study Age 21-45 Able to give informed consent, and comply with study procedures Exclusion Criteria: Current seizure disorder, heart disease or psychiatric disorders (other than cocaine dependence) Dependence on substances other than cocaine or nicotine Request for drug treatment Judged to be noncompliant with study protocol Current use of any medication that has the potential to interact with aripiprazole (i.e., seizure medications, anti-fungal medications, cardiac medications, or medication that produces drowsiness) Clinical laboratory tests outside normal limits that are clinically unacceptable to the study physician (BP > 140/90; BUN, creatinine, LFTs > 1.5 ULN; hematocrit < 34 for women, < 36 for men; pseudocholinesterase deficiency) Currently meeting DSM-IV criteria for all major psychiatric/psychotic disorders other than transient psychosis due to drug abuse Current parole or probation History of significant violent or suicidal behavior

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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
Interventional Model Description: In order to achieve steady-state concentrations, participants (n=8 men) were administered placebo and aripiprazole (15 mg/day) capsules in counter-balanced order for 21 days. A smoked cocaine dose-response curve (0, 12, 25, 50 mg) was determined twice under placebo and aripiprazole maintenance.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aripiprazole (15mg) + Cocaine<br>Aripiprazole (15 mg/day) in conjunction with a smoked cocaine dose-response curve (0, 12, 25, 50 mg). | Drug: Aripiprazole + Cocaine<br>* Participants received aripiprazole (15mg/day) in conjunction with a dose-response of cocaine (0, 12, 25, 50 mg).<br>* Other names: Active;|
| Placebo Comparator: Placebo + Cocaine<br>Placebo (0 mg/day) in conjunction with a smoked cocaine dose-response curve (0, 12, 25, 50 mg) | Drug: Placebo + Cocaine<br>* Placebo (0 mg/day) in conjunction with a dose-response of cocaine (0, 12, 25, 50 mg).<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cocaine Self-administration | Mean number of cocaine choices as a function of cocaine dose and aripiprazole dose (n=8). Participants sampled the dose of cocaine available for the session and then had five choices to respond for money ($5.00) or cocaine using a modified progressive-ratio schedule. | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective Effects of Cocaine | Mean Visual Analog Scale (VAS) ratings (items: Quality, Pay for Dose, Good Drug Effect, and Cocaine Craving) from 0-100mm as a function of cocaine dose and aripiprazole dose 4 min following a single administration of cocaine (the sample dose) at the start of the session. For Quality item, the perceived quality of the drug is rated. The higher the rating, the better quality the drug was perceived to be. For Pay for Dose item, the likelihood that the participant would pay for the drug is indicated. Higher ratings indicate a better likelihood that the person would pay for the dose received. For Good Drug Effect, the likelihood of feeling a good drug effect is indicated. The higher the number, the more of a good drug effect the person reported. For Cocaine Craving, the intensity of craving is reported. Higher scores indicate more craving for cocaine. | 5 days | 
| Plasma Cocaine | Mean plasma cocaine levels after a single administration of each cocaine dose as a function of aripiprazole and cocaine dose. | 8 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aripiprazole, Cocaine abuse