The purpose of this study is to continue our investigation of medications which may be useful in the treatment of cocaine abusers. To date, because of the abundant data from laboratory animals, much research, including ours, has focused on the dopamine system as the target for medications development. That approach has not yet yielded a successful medication. More recent laboratory animal data suggest that GABA may provide a new avenue for pharmacological intervention for the treatment of cocaine abuse. We have selected the GABA analog, gabapentin, which, in addition to its GABA direct activity, has indirect effects on dopamine. We propose to maintain research particpants, in placebo-controlled studies, on gabapentin and evaluate cocaine self-administration, cocaine's subjective effects and cocaine's physiological effects using a progressive ratio self-administration procedure. This use of a medication-maintenance model mimics the treatment situation and increases our ability to detect the effects of active medications, even those with slow onset of therapeutic effects. We believe that this laboratory research with human participants provides the necessary bridge from laboratory to clinic, and allows a relatively short, well controlled and safe alternative to the initial testing of a medication in an open label or even small controlled clinical trial. In addition, use of multiple doses of smoked cocaine provides a sensitive paradigm for detecting small changes in responsivity to cocaine.
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