Allopregnanolone in Short-Term Smoking Abstinence

描述（由申请人提供）：尽管最近在戒烟干预治疗方面取得了进展，但大多数吸烟者在戒烟后不久就会复发。与男性相比，女性复发的风险更高。尽管缺乏临床证据，但最近的研究表明，异孕酮（ALLO）可能对负面药物滥用行为（如自我给药升级和戒断症状的严重程度）有保护作用。ALLO是一种减轻压力的神经活性类固醇，主要由性激素黄体酮代谢；因此，在女性中，它随月经期而变化（卵泡期低水平，黄体期高水平）。在烟草研究、神经内分泌反应、性激素和分析方法方面拥有多学科专业知识的团队，我们将解决以下项目目标-研究ALLO作为防止吸烟复发的潜在神经生物学保护因素的作用。我们将通过对一项正在进行的研究进行二次数据分析来实现这一目标，该研究采用2x2随机交叉设计来评估月经期和情绪对短期戒烟的作用。我们的分析将包括评估月经时间的血清样本，自我报告的戒断措施，以及短期戒烟期间对尼古丁挑战的反应。这项辅助研究提供了一个独特的机会来评估我们的具体研究目的：(1)确认短期戒烟期间ALLO系统水平在月经期的差异；(2)确定短期戒烟期间ALLO系统水平在月经期对尼古丁挑战的反应差异；(3)确定ALLO对短期戒烟期间戒断症状和对尼古丁挑战的反应的影响。如果获得资助，该项目将产生新的信息，阐明性激素代谢物的作用，以及它在女性高吸烟率中的可能贡献。这一信息将直接为戒烟和预防复发干预措施的新研究领域提供信息。

DESCRIPTION (provided by applicant): Despite the recent advancements in smoking cessation intervention treatments, the majority of smokers relapse soon after a quit attempt. Compared to men, women are at an increased risk for relapse. Although the clinical evidence is lacking, recent research suggests that allopregnanolone (ALLO) may be protective against negative drug abuse behaviors such as escalation of self-administration and severity of withdrawal symptoms. ALLO is a stress-reducing neuroactive steroid metabolized primarily from the sex hormone progesterone; therefore, in women, it varies by menstrual phase (low levels in follicular phase; high levels in luteal phase). Employing a multidisciplinary team with expertise i tobacco research, neuroendocrine response, sex hormones and analytical methodology, we will address the following project objective - investigate the role of ALLO as a possible underlying neurobiological protective factor against smoking relapse. We will achieve this objective by conducting a secondary data analyses from an ongoing study that utilizes a 2x2 randomized cross-over design to assess the role of menstrual phase and mood on short-term smoking abstinence. Our analysis will include assessment of menstrually-timed serum samples, self-reported measures of withdrawal, and response to a nicotine challenge during short-term smoking abstinence. This adjunct study provides a unique opportunity to assess our specific study aims: (1) to confirm the menstrual phase differences in systemic levels of ALLO during short-term smoking abstinence, (2) to identify the menstrual phase differences in systemic levels of ALLO in response to a nicotine challenge during short-term smoking abstinence, and (3) to determine the effect of ALLO on withdrawal symptoms and response to a nicotine challenge during short- term smoking abstinence. If funded, this project will result in new information that will shed light on the role a sex hormones metabolite, and its possible contribution in the high rates of smoking relapse among women. This information will directly inform new areas of research on smoking cessation and relapse prevention interventions. PUBLIC HEALTH RELEVANCE: This project aims to characterize the role of allopregnanolone in short-term smoking abstinence in female smokers. Allopregnanolone, a neuroactive steroid that is known to reduce stress, is metabolized from the sex hormone progesterone and may be protective against negative drug abuse behaviors such as escalation of drug use. If allopregnanolone is protective against smoking relapse, this information could be incorporated in smoking cessation interventions to improve smoking cessation rates in women.