Neuroscience-informed Treatment Development for Adolescent Alcohol Use Disorders

青少年酒精使用障碍的神经科学治疗方法开发

• 批准号: 9354398
• 负责人: Lindsay Squeglia
• 金额: $ 20.08万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-20 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9354398
• 关键词: 18 year old; Acetylcysteine; Adolescence; Adolescent; Adult; Age; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohol or Other Drugs use; Alcoholic beverage heavy drinker; Alcohols; Anterior; Antioxidants; Applications Grants; Area; Behavioral; Cannabinoids; Clinical Trials; Cognitive; Cross-Over Studies; Data Set; Development; Disease; Dose; Double-Blind Method; Early Intervention; Evaluation; Evidence based treatment; Functional Magnetic Resonance Imaging; Glutamates; Healthcare Systems; Heavy Drinking; Homeostasis; Human; Image; Imaging Techniques; Laboratories; Laboratory Procedures; Magnetic Resonance Spectroscopy; Marijuana; Marijuana Dependence; Methods; Neurocognitive; Neurosciences; Outcome; Participant; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Placebo Control; Placebos; Preventive Intervention; Procedures; Property; Public Health; Publishing; Randomized; Randomized Controlled Trials; Research; Rewards; Role; Safety; Societies; Substance Use Disorder; Substance of Abuse; System; Testing; Time; Training; United States National Institutes of Health; Urine; Work; Youth; addiction; adolescent alcohol; adolescent substance abuse; adolescent substance use; alcohol cue; alcohol use disorder; career development; cost; cue reactivity; drinking; drinking behavior; emerging adult; experience; heavy drinking during adolescence; improved; meetings; neuroimaging; neuromechanism; novel; patient oriented; pre-clinical; prevent; psychosocial; randomized placebo controlled trial; research clinical testing; social; therapy development; underage drinking

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).

项目概要/摘要 相关性：青少年饮酒是有问题的，并且对认知和社交有长期的负面影响 结果。在早期阶段减少物质使用可能会给人们带来显着的长期利益 心理社会结果并阻止发展成习惯性使用；然而，预防或减少饮酒的努力 青春期使用的效果有限，药物治疗研究的重点是 青少年饮酒的情况一直很少。评估替代和更有效的治疗方法 青少年酗酒者是有理由的。 描述：N-乙酰半胱氨酸 (NAC) 是一种非处方抗氧化剂补充剂，具有谷氨酸能 这些特性在治疗青少年大麻依赖方面显示出希望。临床前发现 表明 NAC 通过恢复因成瘾而破坏的谷氨酸稳态来发挥作用，这一发现得到了重复 跨越多种滥用物质。迄今为止，尚无已发表的临床试验检验 NAC 的功效 酒精的使用。这是令人惊讶的，因为之前 NAC 在大麻依赖青少年中的研究结果很有希望 以及这种非处方补充剂的安全性、耐受性和可负担性。此 K23 应用程序建议 检查 NAC 对酒精提示反应性、青少年谷氨酸系统和饮酒的影响 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 平衡订单中，40 名参与者将接受为期 10 天的 NAC 1200 毫克疗程，每天两次，以及 随后的 10 天疗程中，每天两次使用匹配的安慰剂，中间间隔洗脱期。人体实验室 将在基线时和每个药物治疗疗程后进行影像学检查，以澄清 NAC 对谷氨酸能系统和酒精提示反应性的影响。功能磁共振成像 （功能磁共振成像）将检查酒精反应性，磁共振波谱法将检查酒精中的谷氨酸水平 相同时间间隔内 NAC 后前扣带回与安慰剂的比较。 目的：该提案为申请人提供最佳培训，以获得物质使用障碍方面的专业知识 临床试验研究、针对青少年药物滥用者的循证治疗以及磁共振 进行独立、以患者为导向的发展研究所需的光谱方法和分析 与青少年物质使用和治疗相关的神经机制。这项研究的结果将 帮助确定 NAC 是否可以成为青少年药物滥用者的一种有前途的治疗方法，这是一个研究领域 与跨 NIH 倡议一致，旨在为青少年识别和开发新型药物使用治疗方法 （参见 PA-15-036 和 PA-15-256）。