Pioglitazone for the Treatment of Opioid and of Nicotine Dependence

描述（由申请人提供）：目前，海洛因和处方阿片类药物的滥用在美国是一个普遍的社会问题。同样，美国成年人中吸烟的流行率约为20%，尽管努力减少其使用。我们建议测试吡格列酮的能力，吡格列酮是一种过氧化物酶体增殖体激活受体- γ (PPAR)激动剂，fda批准用于治疗2型糖尿病，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）联合试验。这些研究基于一系列未发表的临床前数据，显示吡格列酮可能在治疗阿片类药物和尼古丁依赖方面具有效用。所有研究的参与者都将住在一个封闭的住院病房，并将在实验室进行测试。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，主观反应，如对药物的喜爱程度、渴望程度和再次吸毒的欲望将被评估。药物组合的潜在毒性将通过测量认知表现和生理反应来评估。这些研究的结果将为吡格列酮与激动剂替代疗法联合使用的效果提供大量信息。如果拟议的研究结果支持吡格列酮的临床前数据，它们可能揭示了药物滥用药物开发的先前未识别的目标。

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 These studies were based on a series of unpublished preclinical data showing that pioglitazone may have utility in treating opioid and nicotine dependence.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).