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; 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).

项目摘要/摘要 相关性：青少年饮酒是有问题的，具有长期的负面认知和社会 结果。在此早期阶段减少物质使用可能会带来重大的长期利益 社会心理结局并阻止习惯使用；但是，预防或减少酒精的努力 青春期的使用仅是适度有效的，药物治疗研究的重点是 青少年饮酒很少。评估替代性和更有效的治疗方法 有必要为青少年酒精使用者提供。 描述：N-乙酰半胱氨酸（NAC）是一种抗谷氨酸能的非处方抗氧化剂补充剂 在青少年治疗大麻依赖方面已显示出希望的特性。临床前发现 建议NAC通过恢复因成瘾而破坏的谷氨酸稳态来起作用，这是复制的发现 跨多种虐待物质。迄今为止，尚无公开的临床试验检查NAC在 饮酒。鉴于以前有希望的大麻依赖性青少年的NAC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。此K23申请提出了 检查NAC对酒精提示反应性，青少年谷氨酸能系统和饮酒的影响 随机，双盲，安慰剂对照的跨界研究中的行为。在 平衡订单，40名参与者将获得10天的NAC 1200毫克，每天两次 随后的10天匹配安慰剂每天两次，按冲洗期分开。人类实验室 并将在基线和每次药物治疗后进行成像程序以澄清 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 （fMRI）将检查酒精反应性和磁共振光谱法将检查谷氨酸水平 NAC与安慰剂后的前扣带回相同的间隔。 目的：该建议为申请人提供最佳培训，以获得药物使用障碍的专业知识 临床试验研究，青少年药物使用者的基于证据的治疗以及磁共振 光谱方法和分析需要进行独立，面向患者的发展研究 关于与青少年物质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是否可以成为青少年药物使用者的有前途的治疗方法，这是一个研究领域 与Trans-NIH倡议一致 （请参阅PA-15-036和PA-15-256）。