Effects of Aripiprazole on Cocaine Craving and Self-Administration

New York State Psychiatric Institute

Status and phase

Completed

Phase 2

Conditions

Cocaine Abuse

Treatments

Drug: Placebo + Cocaine

Drug: Aripiprazole + Cocaine

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00373880

4741

Details and patient eligibility

About

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

Full 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.

Enrollment

26 patients

Sex

All

Ages

21 to 45 years old

Volunteers

Accepts Healthy Volunteers

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