Evaluation of the Electronic Cigarette Withdrawal Syndrome: Mechanistic Targets for Intervention

项目总结摘要 电子烟是当今公共卫生中最重要的问题之一。虽然e- 香烟已经显示出作为传统香烟的戒烟辅助工具的前景，这些香烟对公众健康的好处 产品可能会受到以前对尼古丁天真的年轻人和 这些产品有促进尼古丁依赖的倾向。越来越多的人报告说 想要戒烟但不能成功戒烟，突显了研究的必要性 以确定阻碍电子烟戒烟的因素。当吸烟者突然戒烟时 吸烟，会出现戒断综合症，包括消极情绪和渴望的核心症状， 认知功能受损，睡眠紊乱，所有这些最终都会阻碍戒烟尝试。然而， 关于电子烟戒断的受控研究非常有限，目前还不清楚尼古丁在多大程度上 会导致任何紧急的电子烟戒断综合症。本项目将采用严谨的住宅 评估电子烟戒断表现并实验确定尼古丁作用的实验室设计 在这种综合症中。完全使用电子烟的健康成年人(N=120)将接受电子烟监测 在住宅区七天(一周)以上的禁欲。我们将评估尼古丁对 通过将参与者分配到以下三种条件之一来进行戒断表达：活性尼古丁贴片、安慰剂贴片 控制，或者没有补丁可供控制以满足预期。相关的标准化行为和生物测量 对于包括患者报告、认知任务表现和生物识别在内的撤退，将在整个过程中收集 建立一个严格的戒断时间进程，并评估尼古丁对这些症状的贡献。 设计了三个具体目标来测试尼古丁戒断的核心特征，反映了以下三个核心领域 DSM-5中描述的尼古丁/烟草戒断。具体目标将评估时间进程和贡献 尼古丁对戒断诱导的主观情绪(特定目标1)、认知表现(特定目标1)的影响 目标2)和睡眠障碍(特定目标3)。一个探索性的目标将评估撤军对 动力和回归使用。我们假设负面情绪和渴望会增加，认知表现 在住宅禁欲期间，睡眠将受到损害。我们还假设 与两种对照条件相比，尼古丁贴片可以减轻戒断症状。这项研究将 使用一项严格对照的住院研究，以提供关于 行为和生物方面的电子烟戒断症状，并演示尼古丁在表达中的作用 戒烟以告知转换已建立的和容易获得的尼古丁替代品的可行性 电子烟戒烟的干预措施。

PROJECT SUMMARY ABSTRACT Electronic cigarettes (e-cigarettes) are among the most important issues in public health today. Although e- cigarettes have shown promise as a cessation aid for traditional cigarettes, the public health benefits of these products may be undermined by the soaring rates of initiation among previously nicotine-naïve youth and the propensity for these products to foster nicotine dependence. There are a growing number of people who report wanting to quit using e-cigarettes and not being able to do so successfully, underscoring the need for research to determine factors that impede e-cigarette cessation. When smokers abstain abruptly from combustible cigarette use, a withdrawal syndrome emerges that includes core symptoms of negative affect and craving, impaired cognitive functioning, and disturbed sleep, all of which ultimately hinder cessation attempts. However, there is very limited controlled research on e-cigarette withdrawal, and it is unknown the extent to which nicotine contributes to any emergent e-cigarette withdrawal syndrome. This project will use a rigorous residential laboratory design to evaluate e-cigarette withdrawal expression and experimentally determine the role of nicotine in this syndrome. Healthy adults who exclusively use e-cigarettes (N=120) will undergo monitored e-cigarette abstinence over seven days (1 week) in a residential unit. We will evaluate the contribution of nicotine to withdrawal expression by assigning participants to one of three conditions: active nicotine patch, placebo patch control, or no patch to control for expectancies. Standardized behavioral and biological measures associated with withdrawal including patient report, cognitive task performance, and biometrics will be collected throughout to establish a rigorous timecourse of withdrawal and evaluate the contribution of nicotine to these symptoms. Three Specific Aims are designed to test core features of nicotine withdrawal mirroring three core areas of nicotine/tobacco withdrawal described in the DSM-5. Specific Aims will evaluate the timecourse and contribution of nicotine to withdrawal-induced changes in subjective mood (Specific Aim 1), cognitive performance (Specific Aim 2), and sleep disturbance (Specific Aim 3). An Exploratory Aim will evaluate the impact of withdrawal on motivation and return to use. We hypothesize negative affect and craving will increase, cognitive performance will decrease, and sleep will be impaired during the residential abstinence period. We also hypothesize that withdrawal symptoms will be attenuated with nicotine patch relative to both control conditions. This research will use a rigorously-controlled residential study to provide vital information about the clinical significance of behavioral and biological e-cigarette withdrawal symptoms and demonstrate the role of nicotine in the expression of withdrawal to inform the viability of translating established and readily accessible nicotine replacement interventions to e-cigarette cessation.