A Controlled Trial of N-Acetylcysteine (NAC) in Cannabis Dependent Adolescents

描述(申请人提供)：大麻是美国青少年中最常用的非法物质。大麻对认知、记忆和精神运动技能有深远的影响。在这些领域的最佳表现对于青少年实现过渡到富有成效的成年生活的必要里程碑至关重要。尽管这一严重问题具有潜在的长期后果，但针对这一脆弱年龄段的大麻依赖开发有效治疗方法，特别是药物治疗的调查一直很少。一个潜在的探索途径是开发针对与大麻依赖相关的神经生物学变化的药物，以补充心理社会干预。有希望的临床前和初步临床研究表明，N-乙酰半胱氨酸(NAC)通过谷氨酸调节，在治疗物质使用障碍方面具有潜在的作用。在目前对儿童使用精神药物格外谨慎的气氛下，NAC具有非处方药可用的优势，并在数十年的临床使用中建立了儿科安全记录，使其成为青少年研究的特别有吸引力的候选药物。在令人鼓舞的试点数据的基础上，建议在大麻依赖青少年中进行NAC的安慰剂对照试验。参与者将被随机接受NAC或匹配的安慰剂治疗8周，并在治疗后12周进行额外的随访。所有参与者将同时参加应急管理(CM)干预，旨在加强学习保留和补充针对大麻戒断的药物效果。在整个试验过程中，每周将进行两次尿大麻素测试，认知/冲动测试将在治疗前、治疗期间和治疗后进行。基本假设是，与接受安慰剂+CM的参与者相比，接受NAC+CM的参与者将显示出显著的减少大麻使用(通过尿大麻素阴性测试的数量来衡量)。第二个假设是，大麻使用量的减少(通过尿液大麻素阴性测试的数量来衡量)将与认知/冲动测试成绩的改善有关。另一个次要假设是，与接受安慰剂+CM的参与者相比，接受NAC+CM治疗的尼古丁依赖共病的参与者将表现出吸烟的显著减少(通过尿可替宁验证的自我报告来衡量)。拟议的研究结果可能有助于大麻依赖青少年的治疗发展的新步骤。确定一种耐受性良好、有效的药物治疗来补充现有的心理社会干预措施将是一项重大进步，并可能产生巨大的公共卫生影响。 与公共卫生相关：青春期使用大麻是一个严重的问题，具有潜在的长期后果。到目前为止，开发帮助治疗大麻成瘾青少年的药物的努力微乎其微。因此，拟议的研究将调查N-乙酰半胱氨酸(NAC)，结合循证治疗(应急管理)，以帮助青少年戒除大麻。

DESCRIPTION (provided by applicant): Marijuana is the most commonly used illicit substance among adolescents in the United States. Marijuana has profound effects on cognition, memory, and psychomotor skills. Optimal performance in these domains is critical for adolescents to achieve the necessary milestones for transition to a productive adult life. In spite of this serious problem with potentially long-lasting consequences, there has been minimal investigation targeting the development of effective treatments, particularly medication treatments, for cannabis dependence in this vulnerable age group. A potential avenue for exploration is the development of medication, targeting neurobiological changes associated with cannabis dependence, to complement psychosocial interventions. Promising preclinical and preliminary clinical research indicates a potential role for N-Acetylcysteine (NAC), via glutamate modulation, in the treatment of substance use disorders. With the current climate of extraordinary caution surrounding the use of psychotropic agents in children, NAC has the advantage of over- the-counter availability and established pediatric safety record over decades of clinical use, making it a particularly appealing candidate for research in adolescents. Building upon encouraging pilot data, a placebo-controlled trial of NAC in cannabis dependent adolescents is proposed. Participants will be randomized to receive either NAC or matched placebo for eight weeks, with additional post-treatment follow-up at twelve weeks. All participants will concurrently participate in a contingency management (CM) intervention, designed to enhance study retention and complement medication effect targeting marijuana cessation. Urine cannabinoid tests will be performed twice weekly throughout the trial, and cognitive/impulsivity testing will occur before, during, and after treatment. The primary hypothesis is that participants receiving NAC + CM will exhibit significant reduction in marijuana use (as measured by number of negative urine cannabinoid tests) compared with participants receiving placebo + CM. A secondary hypothesis is that reduction in marijuana use (as measured by number of negative urine cannabinoid tests) will be associated with improvement in cognitive/impulsivity test performance. Another secondary hypothesis is that participants with co-morbid nicotine dependence receiving NAC + CM will exhibit significant reduction in cigarette smoking (as measured by urine cotinine verified self- report) compared with participants receiving placebo + CM. Results of the proposed study may contribute a novel step in treatment development for cannabis dependent adolescents. The identification of a well-tolerated, effective pharmacological treatment to complement existing psychosocial interventions would represent a significant advance and could yield tremendous public health impact. PUBLIC HEALTH RELEVANCE: Marijuana use in adolescence is a serious problem with potentially long-lasting consequences. To date, there has been minimal effort to develop medications to help treat adolescents who are addicted to marijuana. Thus, the proposed study will investigate N-Acetylcysteine (NAC), combined with an evidence-based treatment (Contingency Management), to help adolescents quit using marijuana.