Effects of Aripiprazole on Cocaine Craving and Self-Administration

Phase 2

Completed

Conditions: Cocaine Abuse

Interventions: Drug: Aripiprazole + Cocaine
Drug: Placebo + Cocaine

Registration Number: NCT00373880

Lead Sponsor: New York State Psychiatric Institute

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

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 26

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Aripiprazole (15mg) + Cocaine	Aripiprazole + Cocaine	Aripiprazole (15 mg/day) in conjunction with a smoked cocaine dose-response curve (0, 12, 25, 50 mg).
Placebo + Cocaine	Placebo + Cocaine	Placebo (0 mg/day) in conjunction with a smoked cocaine dose-response curve (0, 12, 25, 50 mg)

Primary Outcome Measures

Name	Time	Method
Cocaine Self-administration	5 days	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.

Secondary Outcome Measures

Name	Time	Method
Plasma Cocaine	8 minutes	Mean plasma cocaine levels after a single administration of each cocaine dose as a function of aripiprazole and cocaine dose.
Subjective Effects of Cocaine	5 days	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.