Human Laboratory Screening of Semaglutide for Alcohol Use Disorder

项目摘要 药物治疗的发展仍然是减少相关健康和社会负担的关键目标 酒精使用障碍（AUD）为特定的AUD亚组开发靶向治疗是一个关键目标 根据NIAAA药物开发战略。在AUD患者中，吸烟者占 长期健康风险极高的重要亚组，因此， 同时存在AUD和吸烟的先进疗法。最近的临床前证据表明， 胰高血糖素型肽-1，一种肠促胰岛素激素，影响酒精动机和摄入。到目前为止，还没有研究表明 报告了GLP-1受体药物对人类酒精动机和奖励方面的影响 参与者人体实验室药物试验为临床前验证提供了一种具有时间和成本效益的选择 在进行更大规模的随机对照试验之前，该项目将利用人类实验室 评估GLP-1受体激动剂作为吸烟者新候选疗法的筛选程序， 澳元。符合AUD标准并报告定期轻度至中度吸烟的受试者将完成 酒精管理程序在一个受试者内，平衡设计。这项研究将提供初步的 GLP-1受体激动剂对酒精相关结局影响的人体数据，包括 酒精和尼古丁的动机，在参与者与AUD。验证用于关节炎的候选单药治疗 减少酒精和尼古丁可能对公众健康产生重大影响。

PROJECT SUMMARY Pharmacotherapy development remains a critical objective for reducing health and societal burdens associated with alcohol use disorder (AUD). Developing targeted treatments for specific AUD subgroups is a key aim under the NIAAA medication development strategy. Among those with AUD, cigarette smokers comprise a sizable and critical subgroup with disproportionally high long-term health risks, making it a key priority to advance therapies for concurrent AUD and cigarette smoking. Recent preclinical evidence indicates that glucagon-type peptide-1, an incretin hormone, impacts alcohol motivation and intake. So far, no studies have reported on the effects of GLP-1 receptor medications on aspects of alcohol motivation and reward in human participants. Human laboratory medication trials offer a time- and cost-effective option for validating preclinical findings prior to carrying out larger randomized controlled trials. This project will utilize human laboratory screening procedures to evaluate a GLP-1 receptor agonist as a novel candidate therapy for smokers with AUD. Participants who meet criteria for AUD and report regular light-to-moderate smoking will complete alcohol administration procedures in a within-subjects, counter-balanced design. This study will provide initial human data on the effects of a GLP-1 receptor agonist in relation to alcohol-related outcomes, including both alcohol and nicotine motivation, in participants with AUD. Validation of a candidate monotherapy for joint alcohol and nicotine reduction could have substantial public health impact.