Evaluating N-acetylcysteine as a pharmacotherapy for tobacco use disorder

项目摘要/摘要 在美国，吸烟是可预防的死亡的主要原因。鉴于这种故态复萌 吸烟是任何特定戒烟尝试最有可能的结果，因此迫切需要扩大治疗 烟草使用障碍(TUD)的选择，以改善持续戒烟和防止再次吸烟。 临床前文献强调谷氨酸在物质使用障碍中的作用，建议治疗的新靶点 药物治疗应以恢复谷氨酸能功能为重点。一种谷氨酸能药物 N-乙酰半胱氨酸(NAC)是一种安全且耐受性良好的药物，最近引起了人们的极大关注 这已经显示出作为一种广泛的药物使用障碍的药物疗法的希望，包括TUD。 初步临床研究表明，NAC的安全性、耐受性和潜在的促进作用 戒除几种滥用药物的行为。然而，随机临床试验的结果好坏参半。AS 作为一种治疗TUD的药物疗法，到目前为止，与NAC进行的工作仅限于试点研究， 总体上是令人鼓舞的，但也有一些喜忧参半。根据文献，知识中的两个缺口 关于治疗TUD的NAC已经出现：1)NAC在启动戒酒方面有效吗；2)NAC对 预防复发，在禁欲一段时间后(或两者兼而有之)。建议的R34将通过以下方式解决这些差距 评价NAC作为治疗TUD的药物疗法。为了严格测试NAC的初始戒断和 预防复发，参与者将被临时加强戒烟三天，同时 接受NAC(每天2400毫克)或与之匹配的安慰剂治疗。参与者将通过以下方式验证禁欲 呼气一氧化碳(CO)样本每天远程采集两次。在经过三天的强化训练后 禁欲，参与者将完成为期8周的治疗干预，在此期间他们将继续服用NAC 或者安慰剂。这项研究将检验与安慰剂相比，NAC在帮助吸烟者实现 连续戒酒三天(目标1)，检查在8周干预期间复发的时间 在NAC组和安慰剂组之间，在禁欲3天的人中(目标2)，并评估 在为期8周的治疗结束研究访问(目标3)时，7天的时点戒断率。结果将通知 治疗文献，并更好地理解如何最好地将NAC用作戒烟 为吸烟者提供最佳治疗效果的药物治疗。来自临床文献的混合结果 有关新来港定居人士的成效显示，从建议的申请中所获取的知识在 在更大的随机对照试验中实施NAC或用于临床人群。由此得出的结论 试验可能会产生显著的影响，因为NAC可以被用作联合治疗和禁欲的一部分- 有针对性的药物治疗或行为干预，除了提供必要的初步数据外 用于NAC治疗TUD的全功率随机对照试验(R01)。

Project Summary/Abstract Cigarette smoking is the leading cause of preventable death in the United States. Given that relapse to smoking is the most likely outcome of any given quit attempt, there is a pressing need to expand treatment options for tobacco use disorder (TUD) to improve sustained abstinence and prevent relapse to smoking. Preclinical literature highlights the role of glutamate in substance use disorders, suggesting that new targets for pharmacotherapy should focus on the restoration of glutamatergic function. One glutamatergic agent that has garnered significant attention recently is N-acetylcysteine (NAC), which is a safe and well tolerated medication that has shown early promise as a pharmacotherapy for substance use disorders broadly, including TUD. Preliminary clinical studies have demonstrated NAC's safety, tolerability, and potential efficacy for promoting abstinence from several drugs of abuse. However, results from randomized clinical trials have been mixed. As a pharmacotherapy for TUD, work conducted with NAC up to this point has been limited to pilot studies, which have been generally encouraging, but also somewhat mixed. Based on the literature, two gaps in knowledge regarding NAC for TUD have emerged: 1) is NAC effective in initiating abstinence; and 2) is NAC effective for relapse prevention, following a period of abstinence (or both). This proposed R34 will address these gaps by evaluating NAC as a pharmacotherapy for TUD. In order to rigorously test NAC for both initial cessation and relapse prevention, participants will be contingently reinforced for abstinence from smoking for three days while undergoing NAC (2400 mg per day) or matched placebo treatment. Participants will verify abstinence through breath carbon monoxide (CO) samples taken remotely twice per day. Following three days of reinforced abstinence, participants will complete an 8-week treatment intervention, in which they will continue to take NAC or placebo. This study will examine the efficacy of NAC, compared to placebo, in helping smokers achieve three days of continuous abstinence (Aim #1), examine the time to relapse over the 8-week intervention between NAC and placebo groups, among those who were abstinent for the 3-day period (Aim #2), and assess 7-day point prevalence abstinence at the 8-week end-of-treatment study visit (Aim #3). Results will inform the treatment literature and provide a better understanding of how NAC is best used as a smoking cessation pharmacotherapy to achieve the best treatment outcomes for smokers. Mixed results from the clinical literature on NAC's efficacy suggest that the knowledge to be gained from the proposed application is essential prior to implementing NAC in larger randomized controlled trials or for use in a clinical population. Findings from this trial may have notable impact, as NAC could be used as part of combination treatment with abstinence- targeted pharmacotherapies or behavioral interventions, in addition to providing the preliminary data necessary for a fully-powered randomized controlled trial (R01) of NAC for TUD.