Effect of sex differences and concurrent cannabis use on stress-related psychobiological mechanisms associated with smoking cessation and relapse

摘要 戒烟干预措施(药理和行为)和政策行动总体上有所减少 吸烟率。然而，仍有大量人口的成功率低于预期， 最值得注意的是使用其他物质的吸烟者和有精神障碍的人。大麻，最多的 在美国和烟草使用者中流行的非法药物，可能会增加再次吸烟的风险。 压力是烟草和烟草中最常见的吸烟和复发的诱因之一。 大麻吸毒者。参与应激反应的系统，包括下丘脑-垂体-肾上腺皮质 (HPA)、内源性大麻素和交感系统在调节情绪和加强 药物使用的影响。我们当前和之前资助时期的研究表明，吸烟者 证据：1)基础HPA活性增强；2)皮质醇对多种应激源反应迟钝；3)阿片类药物中断 应激反应的调节；4)减弱的应激反应与早期吸烟复发的关联；以及 5)复发预测因素的性别差异--男性表现出一致的荷尔蒙预测，而 女性表现出持续的戒断症状，预示着吸烟复发。目前还不清楚是否 吸烟者观察到的改变的应激反应因共同使用大麻而进一步加剧。这些系统如何 被戒断和影响复发的风险也是未知的。解说性的研究 这些因素之间的差异尤其缺乏。我们建议阐明与应激相关的心理生物学 与同时使用大麻有关的阻碍成功戒烟的机制， 在确定后，可用作确定和定制干预措施的指标。因此，我们将进行这项工作 研究：1)确定同时吸食大麻对应激的心理生物学机制的影响 有兴趣戒烟但仍在随意吸烟的吸烟者的反应，2)决定 戒除大麻和戒烟对压力反应的影响 对戒烟感兴趣的吸烟者，3)检查在广告期间的压力反应程度 吸烟和戒烟期间吸烟，或戒烟和大麻，都能预测情感 精神障碍和吸烟在三个月内复发，以及4)发现昼夜模式和性别差异 吸烟者和共同吸烟者在随意吸烟和戒烟期间的应激反应，并确定程度 这些差异预示着该病会复发。拟议的工作将建立在我们之前的研究基础上，为 对于涉及个性化药物方法来预测吸烟复发的干预措施。这将使 制定和测试有针对性的、针对性别的、及时的干预措施，以应对压力的影响 以及联合使用大麻戒烟。

Abstract Smoking cessation interventions (pharmacological and behavioral) and policy actions have reduced overall smoking rates. However, there remain significant populations for whom success rates are lower than predicted, most notably smokers who use other substances and those with psychiatric disorders. Cannabis, the most prevalent illicit drug in the U.S. and among tobacco users, may increase risk for relapse to cigarette smoking. Stress is one of the most commonly reported precipitants of smoking and relapse for both tobacco and cannabis users. Systems involved in the stress response, including the hypothalamic-pituitary-adrenocortical (HPA), endocannabinoid, and sympathetic systems, play a critical role in regulating mood and the reinforcing effects of drug use. Research from our current and previous funding periods has shown that cigarette smokers exhibit: 1) enhanced basal HPA activity; 2) blunted cortisol response to multiple stressors; 3) disrupted opioid regulation of the stress response; 4) association of attenuated stress response and early smoking relapse; and 5) sex differences in patterns of predictors of relapse-- men exhibit consistent hormonal prediction, while women show consistent withdrawal symptoms predictive of smoking relapse. It is not known whether the altered stress response observed in smokers is further exacerbated by cannabis co-use. How these systems are modified by withdrawal and influence risk for relapse is also unknown. Research to elucidate sex differences in these factors is particularly lacking. We propose to elucidate stress-related psychobiological mechanisms associated with concurrent cannabis use that impede successful smoking cessation and which, when identified, can be used as metrics to identify and tailor interventions. We will therefore conduct this research to: 1) Define the impact of concurrent cannabis use on the psychobiological mechanisms of the stress response in smokers who are interested in quitting but still smoking ad libitum, 2) determine the impact of abstinence from cannabis use, in conjunction with abstinence from cigarette smoking, on stress response in smokers who are interested in tobacco cessation, 3) examine the extent to which stress response during ad libitum smoking and during abstinence from tobacco, or from tobacco and cannabis, predict affective disturbance and smoking relapse over three months, and 4) identify sex differences in diurnal patterns and the stress response during ad libitum smoking and withdrawal in smokers and co-users, and establish the extent to which these differences predict relapse. The proposed work will build on our previous research to set the stage for interventions that involve a personalized medicine approach to predicting smoking relapse. This will enable the development and testing of targeted, sex-specific, just-in-time interventions to address the impact of stress and co-use of cannabis on smoking cessation.