Assessment of Pioglitazone to Address Stress Reactivity and Alcohol Use Disorder

吡格列酮解决应激反应和酒精使用障碍的评估

• 批准号: 10491667
• 负责人: Jin Ho Yoon
• 金额: $ 18.53万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10491667
• 关键词: Address; Affect; Agonist; Alcohol consumption; Alcohol withdrawal syndrome; Alcohols; Animal Experimentation; Anti-Inflammatory Agents; Anxiety; Attention; Attenuated; Behavioral; Biological; Blood Pressure; Data; Diabetes Mellitus; Disulfiram; Dose; Double-Blind Method; Environment; Exhibits; FDA approved; Health; Heart Rate; Heavy Drinking; Human; Hydrocortisone; Hypothalamic structure; Individual; Laboratories; Life; Measures; Metabolic Diseases; Modeling; Modernization; Naltrexone; Opioid; Outcome; PPAR gamma; Participant; Peroxisome Proliferator-Activated Receptors; Pharmaceutical Preparations; Pharmacotherapy; Pilot Projects; Pioglitazone; Pituitary Gland; Placebos; Process; Psychometrics; Public Health; Rattus; Reporting; Research; Rewards; Role; Salivary; Sampling; Single-Blind Study; Societies; Standardization; Stress; System; Time; Time Factors; Withdrawal Symptom; acamprosate; addiction; alcohol abuse therapy; alcohol availability; alcohol craving; alcohol demand; alcohol use disorder; behavioral economics; craving; discounting; drinking; economic cost; eligible participant; model design; new therapeutic target; novel; pre-clinical; relapse risk; response; screening; social; stress reactivity; theories; therapeutic target; tool

ABSTRACT Alcohol use disorder (AUD) is significant public health concern. Stress is a central component in modern theories of alcohol use, and stress is intimately related to drinking for many individuals. There are a number of approved medications for AUD, but the majority of individuals do not respond to these medications and no medications address the role of stress. The current proposal looks affect alcohol use by targeting stress-related systems in the body through peroxisome proliferator-activated receptors (PPARs), which may effect stress reactivity, stress-induced alcohol craving, and alcohol use. Pioglitazone (Actos) targets PPARγ and is FDA- approved for treating individuals with diabetes and metabolic disorders. Promising results from both human trials and animal research suggest that pioglitazone holds great promising for addressing AUD, including preliminary data from our own research. The current proposal will attempt to expand on our preliminary findings targeting alcohol use among treatment-seeking individuals with AUD and elevated stress and/or anxiety with the following specific aims: 1) to assess if pioglitazone decreases stress reactivity and stress- induced craving in a human laboratory model; and 2) to assess if pioglitazone changes weekly psychometric reports of stress/anxiety, craving, and alcohol consumption. Notable strengths of the current proposal include: 1) targeting individuals with elevated stress/anxiety and AUD; 2) biological assessment of stress reactivity (heart rate, blood pressure, salivary cortisol); 3) a multi-dimensional assessment of alcohol craving incorporating relatively novel behavioral economic measures (i.e., alcohol demand, delay discounting); and 4) inclusion of powerful Bayesian statistical tools that are well suited for smaller samples, such as the current proposal.

抽象的 酒精使用障碍（AUD）是重大的公共健康问题。 饮酒理论和压力与许多人的饮酒有关。 批准了AUD的药物，但大多数人对这些医学没有反应 药物应对压力的作用。 体内的系统Throgh过氧化物酶体增殖物激活受体（PPAR），这可能会影响应力 反应性，应力诱导的酒精渴望和饮酒。 批准治疗糖尿病和代谢障碍的人。 试验和动物研究表明，对AUD的讲话很有希望，包括 来自自己的研究的初步数据将尝试扩展我们的初步 针对具有AUD和升高压力升高的寻求治疗的个人和OS或或或或或或或或或或或或或或以或或或或或或或或 以下特定目的的焦虑：1）评估吡格列酮是否减少了压力条纹和条纹 - 在人类实验室模型中引起的渴望； 2） 压力/焦虑，渴望和饮酒的报道。 1）靶向应力/焦虑和AUD的个体； 2）压力反应性的生物学评估 （心率，血压，唾液皮质醇）； 3）渴望的多维评估 纳入相对新颖的行为经济措施（即酒精需求，延迟折现）和4）； 包括功能强大的贝叶斯统计工具工具，非常适合较小的样品，例如当前 提议。