Pioglitazone for the Treatment of Opioid and of Nicotine Dependence

描述(申请人提供)：目前，海洛因和处方阿片类药物的滥用在美国是一个普遍存在的社会问题。类似地，美国成年人中烟草使用的流行率约为20%，尽管人们正在加紧努力减少烟草的使用。我们建议测试吡格列酮的能力，它是一种过氧化物酶体增殖物激活的受体-伽马(PPAR)激动剂，FDA批准用于治疗2型糖尿病，以减少海洛因滥用(研究1)和吸烟(研究2)。吡格列酮将与丁丙诺啡/纳洛酮(研究1)和尼古丁贴片(研究2)联合进行测试。这些研究基于一系列未发表的临床前数据，表明吡格列酮可能在治疗阿片类药物和尼古丁依赖方面有用。所有研究的参与者都将住在一个上了锁的住院病房里，并将在实验室接受测试。将评估吡格列酮改变药物自我给药、对药物线索的反应性和药物复发的能力。此外，还将评估主观反应，如对药物的喜好、渴望和再次服用药物的愿望的评分。将通过测量认知表现和生理反应来评估药物组合的潜在毒性。这些研究的结果将提供大量关于吡格列酮与激动剂替代疗法联合治疗的效果的信息。如果建议的研究结果支持吡格列酮的临床前数据，他们可能会揭示一个以前未确定的药物滥用药物开发的靶点。 与公共健康相关：海洛因和处方阿片类药物滥用在美国很普遍，吸烟也是如此。本提案的目的是描述目前用于治疗糖尿病的药物吡格列酮改变海洛因(研究1)和吸烟(研究2)滥用倾向的能力。吡格列酮将与丁丙诺啡/纳洛酮(研究1)或尼古丁贴片(研究2)联合使用。

DESCRIPTION (provided by applicant): Currently, the abuse of heroin and prescription opioid medications is a pervasive social problem in the U.S. Similarly, the prevalence of tobacco use among adults in the U.S. is approximately 20%, despite intensive efforts to reduce its use. We are proposing to test the ability of pioglitazone, a peroxisome proliferator-activated receptor- gamma (PPAR) agonist that is FDA-approved for use in the management of type 2 diabetes mellitus, to reduce abuse of heroin (Study 1), and cigarette smoking (Study 2). Pioglitazone will be tested in combination with buprenorphine/naloxone (Study 1) and with the nicotine patch (Study 2). These studies were based on a series of unpublished preclinical data showing that pioglitazone may have utility in treating opioid and nicotine dependence. Participants in all studies will live on a locked inpatient unit and will be tested in the laboratory. The ability of pioglitazone to alter drug self-administration, reactivity to drug cues, and relapse to drug use will be assessed. In addition, subjective responses, such as ratings of drug liking, craving, and desire to take the drug again will be evaluated. Potential toxicity of the medication combinations will be assessed by measuring cognitive performance and physiological responses. The results of these studies will provide a great deal of information about the effects of pioglitazone in combination with agonist replacement therapies. If the results of the proposed studies support the preclinical data with pioglitazone, they may reveal a previously unidentified target for medications development for substance abuse. PUBLIC HEALTH RELEVANCE: Heroin and prescription opioid abuse are prevalent in the U.S., as is cigarette smoking. The purpose of the present proposal is to characterize the ability of pioglitazone, a medication currently used to treat diabetes, to alter the abuse liability of heroin (Study 1) and of cigarette smoking (Study 2). Pioglitazone will be given in combination with buprenorphine/naloxone (Study 1) or the nicotine patch (Study 2).