An Addictions Neuroclinical Assessment Based Treatment for Smokers with an Alcohol Use Disorder

项目总结/摘要 在美国，烟草和酒精每年造成50多万人死亡，使共同- 对这些物质上瘾是可预防死亡的主要原因。我们提出一个应急管理 (CM)基于测量乙基葡萄糖醛酸苷的即时尿检的范例。理论上， 成瘾神经临床评估（ANA）在核心域中具有假设的机制（即，激励 突出性、消极情绪和认知功能），并从一个健全和创新的科学 在此前提下，我们将首次通过实施一项基于证据的行为计划， 已开始一线药物治疗（伐尼克兰; VC）的受试者中的酒精治疗（CM） 为了戒烟。该项目旨在复制，利用和扩展我们以前的研究结果，从中学 分析和试点研究表明，将CM应用于针对酒精使用的目标可以产生非 有针对性地减少吸烟。我们将通过向同时吸烟的人提供用于酒精使用的CM来做到这一点。 开始戒烟药物治疗。我们还寻求确定最有效的ANA为基础的调解人 (e.g.,激励显著性（考虑到CM重点是替代强化）的行为变化的响应 接受治疗最后，我们将研究生物性别和基线饮酒和吸烟的程度， 吸烟与CM相互作用，产生不同程度的减少酒精使用和吸烟。患者将 参加一项2组随机对照试验，以评估CM干预减少酒精使用的能力 和吸烟。完成2周诱导期后，患者将被随机分配至2个试验组 为期12周的治疗期：1）CM干预组，照常接受戒烟治疗 (TAU)，包括伐尼克兰和咨询，以及2）非偶然（NC）对照组，也接受 τ的我们的具体目标是：1）确定CM+TAU是否比NC+TAU更有效地减少酒精 使用和吸烟。我们假设，CM将产生较低的生化验证酒精使用率 和吸烟，同时使用生物化学验证的酒精和吸烟，以及自我报告的饮酒量， 在12周的治疗和6个月的随访期间，每天吸烟，每天大量饮酒。 3)确定各治疗组中最有效的基于ANA的治疗反应介质。我们 假设更高的执行功能障碍，消极情绪，酒精和吸烟相关的诱因 显著性将与更高水平的酒精使用和吸烟相关， 3）确定生物性别或基线严重程度的饮酒和吸烟是否与治疗相互作用 分配给我们的主要和次要结果产生不同的变化。我们假设 生物性别将与治疗产生显著的相互作用，以产生不同的结果，而那些具有较少 基线时饮酒和吸烟的严重程度将经历更好的结果。这项调查将支持 未来的研究，可以确定个性化治疗的不同亚组的吸烟者与AUD。

PROJECT SUMMARY/ABSTRACT Together, tobacco and alcohol kill more than half a million people in the United States every year, making co- addiction to these substances the leading cause of preventable death. We propose a contingency management (CM) paradigm based on point-of-care urine tests that measure ethyl glucuronide. Theoretically framed within the Addiction Neuroclinical Assessment (ANA) with hypothesized mechanisms in core domains (i.e., incentive salience, negative emotionality and cognitive function), and proceeding from a sound and innovative scientific premise, we will, for the first time, target smoking and alcohol use by implementing an evidence-based behavioral treatment (CM) for alcohol among participants who have initiated frontline pharmacotherapy (varenicline; VC) for smoking cessation. This project seeks to replicate, harness and extend our previous findings from secondary analyses and pilot studies, which demonstrate that applying CM to target the use of alcohol can produce non- targeted reductions in smoking. We will do so by offering CM for alcohol use to smokers who are simultaneously initiating smoking cessation pharmacotherapy. We also seek to identify the most potent ANA-based mediators (e.g., incentive salience given that CM’s focus is on alternative reinforcement) of behavior change in response to treatment. Lastly, we will examine the extent to which biologic sex and baseline alcohol use and cigarette smoking interacts with CM to produce different levels of reduced alcohol use and cigarette smoking. Patients will take part in a 2-arm randomized controlled trial to evaluate the ability of a CM intervention to reduce alcohol use and cigarette smoking. After completing a 2-week induction period, patients will be randomized into 2 trial arms for a 12-week treatment period: 1) a CM intervention group that receives smoking cessation treatment as usual (TAU), which includes varenicline and counseling, and 2) a non-contingent (NC) control group that also receives TAU. Our Specific Aims are to: 1) Determine if CM+TAU is more effective than NC+TAU for reducing alcohol use and cigarette smoking. We hypothesize that CM will yield lower rates of biochemically-verified alcohol use and cigarette smoking, concurrent biochemically-verified alcohol use and smoking, and self-reported drinks per day, cigarettes per day, and heavy drinking days during the 12-week treatment and 6-month follow-up periods. 3) Identify the most potent ANA-based mediators of treatment response across the treatment groups. We hypothesize that higher executive dysfunction, negative emotionality, and alcohol- and smoking-related incentive salience will be associated with higher levels of alcohol use and cigarette smoking across treatments and over time; 3) Determine if biological sex or baseline severity of alcohol use and smoking interacts with treatment assignment to produce differential changes in our primary and secondary outcomes. We hypothesize that biological sex will significantly interact with treatment to produce differential outcomes, and that those with less severity of alcohol use and smoking at baseline will experience better outcomes. This investigation will support future studies that can identify personalized treatment for different sub-groups of smokers with an AUD.