Modeling Initial Smoking Abstinence and Relapse Risk

描述(申请人提供)：在美国，吸烟是可预防的死亡的主要原因。绝大多数试图戒烟的人在戒烟努力的最初两周内会复发。重要的是，在最初的几周里保持禁欲与复发风险的急剧下降有关。这一竞争性持续应用程序的第一次修订的总体目标是继续一个项目，重点是开发和应用人体实验室模型，用于实验分析持续戒烟初期如何降低复发风险。在这个模型中，吸烟者被随机分配到条件下，在这些条件下，他们根据实现不同时间的戒烟而获得金钱强化。参与者在两周内每天向实验室报告，以核实吸烟状况，填写受试者评价表，并参与行为和其他测试。使用该模型在前一资助期间进行的一系列实验的结果表明，持续戒烟的初期可能通过以下方式降低复发风险：(1)减少尼古丁的戒断和渴求，(2)降低对吸烟积极和消极强化的预期，(3)减少吸烟的相对强化效应，以及(4)增加受试者戒烟的易感性和对戒烟能力的信心。 在这个修订的应用中，我们建议扩大这个模型的范围，包括使用fMRI评估禁欲对线索反应性、抑制性反应和相关脑活动的影响。实验1将对最初的戒烟对行为、认知和神经生物学功能的扩展组的影响进行彻底的参数评估。实验2和实验3将使用该模型来检查两种有效的戒烟药物疗法(尼古丁替代疗法和varenicline)如何增强或以其他方式改变持续戒烟初期的效果。众所周知，这些药物可以增加最初的禁酒率，但关于它们是如何做到的，特别是对大脑功能的影响，还有很多需要了解。总体而言，拟议的研究有可能为在最初戒烟期间发生的行为、认知和神经生物学变化提供重要的新科学知识，这些变化可能直接降低复发风险。这些知识可能会为如何更好地针对治疗干预提供洞察力，并以这种方式帮助更多的人成功戒烟。 与公共健康相关：在美国，吸烟是可预防的死亡的主要原因。试图戒烟的人的复发模式表明，那些能够坚持戒烟最初两周的人，长期成功的机会显著增加。这个项目的重点是通过实验分析在持续禁欲的最初几周内发生的行为、认知和神经生物学变化，并阐明它们如何为一个人的长期成功做好准备。

DESCRIPTION (provided by applicant): Cigarette smoking is the leading cause of preventable death in the U.S. The vast majority of individuals who attempt to quit smoking will relapse within the initial two weeks of the cessation effort. Importantly, sustaining abstinence through those initial weeks is associated with a precipitous decrease in relapse risk. The overarching aim of this 1st revision of a competing continuation application is to continue a project focused on the development and application of a human-laboratory model for experimentally analyzing how an initial period of sustained smoking abstinence may reduce relapse risk. In this model, smokers are randomly assigned to conditions in which they earn monetary reinforcement contingent on achieving varying durations of smoking abstinence. Participants report to the laboratory daily for two weeks to verify smoking status, complete subject-rating forms, and participate in behavioral and other testing. Results from a series of experiments conducted during the prior funding period using this model suggest that an initial period of sustained abstinence may lower relapse risk by (1) decreasing nicotine withdrawal and craving, (2) decreasing expectations of positive and negative reinforcement from smoking, (3) decreasing the relative reinforcing effects of smoking and (4) increasing subjects' perceived ease of abstaining and confidence in their ability to abstain. In this revised application we propose to expand the scope of this model by including assessments of abstinence effects on cue reactivity, inhibitory responding, and associated brain activity using fMRI. Experiment 1 will be a thorough, parametric assessment of initial smoking abstinence effects on this expanded battery of behavioral, cognitive, and neurobiological functioning. Experiments 2 and 3 will use the model to examine how two efficacious pharmacotherapies for smoking cessation (nicotine replacement therapy and varenicline) enhance or otherwise alter the effects of an initial period of sustained abstinence. These medications are known to increase initial abstinence rates, but much remains to be learned about how they do so especially their effects on brain function. Overall, the proposed studies have the potential to contribute important new scientific knowledge regarding behavioral, cognitive, and neurobiological changes that occur during initial smoking abstinence that may directly reduce relapse risk. Such knowledge may provide insights into how to better target therapeutic interventions and in that manner help more people succeed in quitting smoking. PUBLIC HEALTH RELEVANCE: Cigarette smoking is the leading cause of preventable death in the U.S. Relapse patterns among those attempting to quit smoking suggest that those who are able to persevere through the initial two weeks of trying to quit have a strikingly improved chance of long-term success. This project is focused on experimentally analyzing behavioral, cognitive, and neurobiological changes that occur during those initial weeks of sustaining abstinence and elucidating how they may position a person for longer-term success.