Pioglitazone for the Treatment of Opioid and of Nicotine Dependence

吡格列酮用于治疗阿片类药物和尼古丁依赖

• 批准号: 8487385
• 负责人: ADAM BISAGA
• 金额: $ 83.35万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8487385
• 关键词: Abstinence; Adult; Agonist; Area; Behavior; Behavioral; Buprenorphine; Cigarette; Cigarette Smoker; Cognitive; Combination Medication; Cues; Data; Dependence; Development; Diabetes Mellitus; Dose; Double-Blind Method; Drug Addiction; Drug abuse; Drug usage; Effectiveness; FDA approved; Focus Groups; Goals; Heroin; Heroin Abuse; Human; Individual; Inpatients; Investigation; Laboratories; Laboratory Study; Life; Marketing; Measures; Methadone; Microglia; Minocycline; Modeling; Morphine; Naloxone; Neuroglia; Nicotine; Nicotine Dependence; Nicotine Withdrawal; Nicotinic Receptors; Non-Insulin-Dependent Diabetes Mellitus; Opiate Addiction; Opioid; Opioid Receptor; PPAR gamma; Participant; Pathway interactions; Patients; Performance; Pharmaceutical Preparations; Pharmacotherapy; Physiological; Pioglitazone; Placebo Control; Placebos; Play; Prevalence; Randomized; Rattus; Relapse; Replacement Therapy; Research; Resistance; Rewards; Role; Rolipram; Safety; Self Administration; Series; Severities; Smoking; Social Problems; Stress; Substance abuse problem; Takeda brand of pioglitazone hydrochloride; Testing; Therapy Clinical Trials; Tobacco use; Toxic effect; Treatment Effectiveness; Yohimbine; base; cigarette smoking; compare effectiveness; craving; design; drug craving; drug maintenance; drug of abuse; improved; inhibitor/antagonist; macrophage; monocyte; nicotine patch; nicotine replacement; novel; opioid abuse; opioid withdrawal; pre-clinical; preclinical study; prescription opioid; prescription opioid abuse; prevent; public health relevance; response; treatment strategy; varenicline; volunteer

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.

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。

项目成果

The effects of heroin administration and drug cues on impulsivity.

• DOI: 10.1080/13803395.2016.1156652
• 发表时间: 2016-08
• 期刊: Journal of clinical and experimental neuropsychology
• 影响因子: 2.2
• 作者: Jones JD;Vadhan NP;Luba RR;Comer SD
• 通讯作者: Comer SD

The PPARγ Agonist Pioglitazone Fails to Alter the Abuse Potential of Heroin, But Does Reduce Heroin Craving and Anxiety.

PPARγ 激动剂吡格列酮无法改变海洛因的滥用潜力，但可以减少海洛因的渴望和焦虑。

• DOI: 10.1080/02791072.2018.1508789
• 发表时间: 2018
• 期刊: Journal of psychoactive drugs
• 影响因子: 2.8
• 作者: Jones,JermaineD;Bisaga,Adam;Metz,VerenaE;Manubay,JeanneM;Mogali,Shanthi;Ciccocioppo,Roberto;Madera,Gabriela;Doernberg,Molly;Comer,SandraD
• 通讯作者: Comer,SandraD