Aripiprazole maintenance increases smoked cocaine self-administration in humans
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Partial dopamine receptor agonists have been proposed as candidate pharmacotherapies for cocaine dependence.
This 42-day, within-subject, human laboratory study assessed how maintenance on aripiprazole, a partial D2 receptor agonist, influenced smoked cocaine self-administration, cardiovascular measures, subjective effects, and cocaine craving in nontreatment-seeking, cocaine-dependent volunteers.
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. Sessions comprised a “sample” trial, when participants smoked the cocaine dose available that session, and five choice trials, when they responded on a progressive-ratio schedule of reinforcement to receive the cocaine dose or receive $5.00.
Cocaine’s reinforcing, subjective, and cardiovascular effects were dose-dependent. Aripiprazole significantly increased cocaine (12, 25 mg) self-administration. Following a single administration of cocaine (25 mg), aripiprazole decreased ratings of how much participants would pay for that dose. Following repeated cocaine (50 mg) self-administration, aripiprazole decreased ratings of cocaine quality, craving, and good drug effect as compared to placebo.
These data suggest that aripiprazole may have increased self-administration to compensate for a blunted subjective cocaine effect. Overall, the findings do not suggest aripiprazole would be useful for treating cocaine dependence.
KeywordsAddiction Antipsychotic Cocaine
The authors would also like to thank the nurses, physicians, and research assistants working in the Marian W. Fischman Cocaine Research Laboratory, and appreciate the contributions of their fellow investigators: Drs. Carl L. Hart, Suzanne Vosburg, Nehal Vadhan, Suzette Evans, and Stephanie Collins Reed.
Dr. Haney received consultant fees from Celtic Pharmaceuticals in 2007. Dr. Foltin currently receives research support for an investigator-initiated protocol from Aztra Zeneca. Dr. Rubin reported no biomedical financial interests or potential conflicts of interest. This research was supported by both NIDA (DA10755/Haney; DA006234/Foltin) and funding from Bristol-Meyers Squibb. Participants resided on the Irving Institute for Clinical and Translational Research of The New York-Presbyterian Medical Center, supported by Grant No. MOI-RR-00645 from the National Institutes of Health.
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