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，但大多数吸烟者在尝试戒烟后很快就会复发。与男性相比，女性复发的风险更高。虽然缺乏临床证据，但最近的研究表明，allopregnanolone（ALLO）可能对消极的药物滥用行为具有保护作用，例如自我管理的升级和戒断症状的严重程度。ALLO是一种主要由性激素孕酮代谢的减压神经活性类固醇;因此，在女性中，它因月经期而异（卵泡期低水平;黄体期高水平）。我们聘请了一支具有烟草研究、神经内分泌反应、性激素和分析方法等专业知识的多学科团队，将致力于以下项目目标-研究ALLO作为防止吸烟复吸的潜在神经生物学保护因子的作用。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，以评估月经期和情绪对短期戒烟的作用。我们的分析将包括对定时血清样本的评估，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标：（1）确认在短期戒烟期间ALLO的全身水平的月经期差异，（2）鉴定在短期戒烟期间响应尼古丁激发的ALLO的全身水平的月经期差异，以及（3）确定ALLO对短期戒烟期间戒断症状和对尼古丁激发反应的影响。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，及其可能导致妇女吸烟复吸率高。这些信息将直接为戒烟和复吸预防干预措施的新研究领域提供信息。 公共卫生相关性：该项目旨在描述别孕烯醇酮在女性吸烟者短期戒烟中的作用。别孕烯醇酮是一种神经活性类固醇，已知可以减轻压力，由性激素孕酮代谢，可以防止负面药物滥用行为，如药物使用的升级。如果allopregnanolone是防止吸烟复吸，这一信息可以纳入戒烟干预措施，以提高妇女戒烟率。

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.