Project 1 will test two new medications for cocaine dependence in late Phase II trials memantine, a non-competitive NMDA antagonist used in Europe to treat dementia, and gabapentin, an anti-convulsant which acts by enhancing GABA activity in the CNS. The pivotal role of dopamine in the rewarding and addictive properties of cocaine remains clear, but the lack of success with anti-depressants and dopamine agonists in clinical trials suggests other approaches to manipulating the dopamine system in cocaine dependent patients should be sought. Excitatory amino acids (EAA) and the inhibitory neurotransmitter gamma amino butyric acid (GABA) exert reciprocal influences on dopamine neurons in the reward system, the former promoting and the latter inhibiting dopamine release. In addition, excitatory amino acids may promote the development of conditioned responses to cocaine cues which perpetuate addiction. This suggests the hypothesis that either EAA antagonists or GABA agonists may be effective for cocaine dependence by reducing cocaine-induced dopamine release and/or attenuating conditioning to cocaine cues. Two 12-week prospective, parallel-groups, randomized, placebo- controlled trials (Study 1: memantine versus placebo; Study B: gabapentin versus placebo) will be conducted in outpatients with cocaine dependence.
The specific aims will be to determine whether memantine (Study A) or gabapentin (Study B) are superior to placebo in reducing cocaine use, cocaine craving, psychological symptoms, functional impairment, and attrition from treatment. In addition, these studies are part of a larger effort in this MDRU to develop optimal clinical trial designs for testing cocaine pharmacotherapies. Patients will be asked to attend the clinic three times weekly for medication and urine monitoring and participate in weekly placebo lead in during which patients will be required to attend at least four out of six visits in order to enter the randomized trial. These design features are intended to produce a compliant sample to maximize power to detect medication effects. Cocaine use during the lead in will be examined as a predictor of cocaine use outcome and of medication effects in order to evaluate the utility of the placebo lead in as a design feature for cocaine medication development trials,
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| Bisaga, Adam; Aharonovich, Efrat; Cheng, Wendy Y et al. (2010) A placebo-controlled trial of memantine for cocaine dependence with high-value voucher incentives during a pre-randomization lead-in period. Drug Alcohol Depend 111:97-104 |
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| Vosburg, Suzanne K; Hart, Carl L; Haney, Margaret et al. (2005) An evaluation of the reinforcing effects of memantine in cocaine-dependent humans. Drug Alcohol Depend 79:257-60 |
