LAB TRIALS TO DEVELOP MEDICATIONS FOR COCAINE DEPENDENCE--STUDY 1

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 托吡酯是一种取代的果糖-吡喃糖衍生物，是一种很有前途的治疗可卡因依赖的药物，可能是因为它减少了与滥用倾向相关的奖励作用。我们提出了一个实验，使用国家的最先进的人类滥用责任评估技术，以检查主观，行为和生理的影响，可卡因单独和与托吡酯相结合。本研究将在男性和女性非治疗寻求可卡因滥用者（总N = 24）中采用平衡（序列和位置）交叉设计进行双盲和安慰剂对照。该实验将检验长期给予托吡酯将显著降低主观情绪和其他滥用倾向评估中可卡因介导的急性变化的假设。作为本实验的次要目的，我们将描述可卡因对非疲劳受试者在服药期间的认知和生理反应的影响，并确定托吡酯是否改变了这些影响以及改变了多少。 总之，该实验提供了托吡酯降低可卡因滥用潜力的能力的概念验证分析。 这项人体实验室研究的结果应该提供一个坚实的基础，计划临床试验检查托吡酯治疗可卡因依赖的个人的安全性和有效性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Topiramate, a substituted fructo-pyranose derivative, is a promising agent for the treatment of cocaine dependence, presumably because by reducing its rewarding affects associated with abuse liability. We propose an experiment using state-of-the-art human abuse liability assessment techniques to examine the subjective, behavioral, and physiological effects of cocaine both alone and in combination with topiramate. The study will be double-blind and placebo-controlled using a balanced (for sequence and position) cross-over design in male and female non treatment-seeking cocaine abusers (total N = 24). The experiment will test the hypothesis that chronically-administered topiramate will significantly reduce acute cocaine-mediated changes in subjective mood and other abuse liability assessments. As a secondary objective of this experiment, we will characterize cocaine's effects on cognition and physiological response in non-fatigued subjects during drug-taking, and determine if, and by how much, these effects are altered by topiramate. In summary, this experiment provides a proof-of-concept analysis of topiramate's ability to reduce cocaine's abuse potential. The results of this human laboratory study should provide a solid basis for planning clinical trials examining the safety and effectiveness of topiramate for the treatment of cocaine-dependent individuals.