Neuroscience-informed Treatment Development for Adolescent Alcohol Use Disorders

项目摘要/摘要 相关性：青少年饮酒是有问题的，并长期对认知和社交产生负面影响 后果。在早期阶段减少药物使用可能会对以下方面产生重大的长期好处 心理社会结果和阻止发展成习惯使用；然而，防止或减少酒精的努力 在青春期使用只有一定的效果，药物治疗研究主要集中在 青少年饮酒的现象一直很少。评估替代和更有效的治疗方法 青少年饮酒者是理所当然的。 描述：N-乙酰半胱氨酸(NAC)是一种含有谷氨酸能的非处方药抗氧化剂 在治疗青少年大麻依赖方面显示出希望的特性。临床前发现 提示NAC通过恢复被成瘾破坏的谷氨酸平衡起作用，这一发现也得到了重复 涉及多种滥用物质。到目前为止，还没有发表的临床试验检验NAC对 酗酒。考虑到之前NAC在大麻依赖青少年中有希望的发现，这是令人惊讶的 以及这种非处方补充剂的安全性、耐受性和可负担性。这个K23应用程序建议 研究NAC对酒精线索反应性、青少年谷氨酸能系统和饮酒的影响 一项随机、双盲、安慰剂对照的受试者内交叉研究中的行为。在……里面 平衡订单，40名参与者将获得为期10天的疗程，每天两次，每次1200毫克，并 随后，每日两次服用10天疗程的匹配安慰剂，以冲洗期分隔。人体实验室 成像程序将在基线和每次药物治疗后进行，以明确 NAC对谷氨酸能系统和酒精线索反应性的影响。功能磁共振成像 (FMRI)将检测酒精的反应性，磁共振波谱将检测人体内的谷氨酸水平 在相同的时间间隔内，NAC后的前扣带回与安慰剂相比。 目的：本建议为申请者提供最佳培训，以获得药物使用障碍方面的专业知识 临床试验研究，青少年药物使用者的循证治疗，以及磁共振 开展独立的、以患者为中心的发展研究所需的光谱方法和分析 与青少年药物使用和治疗相关的神经机制。这项研究的发现将 帮助确定NAC是否可能成为青少年吸毒者的有前途的治疗方法，这是一个研究领域 符合TRANS-NIH为青少年确定和产生新的物质使用治疗方法的倡议 (见PA-15-036和PA-15-256)。

PROJECT SUMMARY/ABSTRACT Relevance: Adolescent alcohol use is problematic and has long-term negative cognitive and social consequences. Decreasing substance use at this early stage could have significant long-term benefits to psychosocial outcomes and deter progression to habitual use; however, efforts to prevent or decrease alcohol use during adolescence have only been modestly effective, and pharmacotherapy research focused on adolescent alcohol use has been sparse. Evaluation of alternative and more efficacious treatments for adolescent alcohol users is warranted. Description: N-acetylcysteine (NAC) is an over-the-counter antioxidant supplement with glutamatergic properties that has shown promise in treating marijuana dependence in adolescents. Preclinical findings suggest NAC works through restoring glutamate homeostasis disrupted by addiction, a finding replicated across multiple substances of abuse. No published clinical trials to date have examined the efficacy of NAC on alcohol use. This is surprising, given previous promising NAC findings in marijuana-dependent adolescents and the safety, tolerability, and affordability of this over-the-counter supplement. This K23 application proposes to examine the effects of NAC on alcohol cue reactivity, adolescent glutamatergic systems, and drinking behaviors in a randomized, double-blind, placebo-controlled within-subjects crossover study. In counterbalanced order, 40 participants will receive a 10-day course of NAC 1200 mg twice daily and a subsequent 10-day course of matched placebo twice daily, separated by washout period. Human laboratory and imaging procedures will be conducted at baseline and after each course of medication treatment to clarify NAC's effect on glutamatergic systems and alcohol cue reactivity. Functional magnetic resonance imaging (fMRI) will examine alcohol reactivity and magnetic resonance spectroscopy will examine glutamate levels in the anterior cingulate after NAC versus placebo over the same interval. Aims: This proposal provides optimal training for the applicant to gain expertise in substance use disorder clinical trials research, evidence based treatments for adolescent substance users, and magnetic resonance spectroscopy methods and analysis needed to conduct independent, patient-oriented, developmental research on neural mechanisms associated with adolescent substance use and treatment. Findings from this study will help establish if NAC could be a promising treatment for adolescent substance users, an area of research that is consistent with trans-NIH initiative to identify and generate novel substance use treatments for adolescents (see PA-15-036 and PA-15-256).