Cognitive Recovery With Cannabis Abstinence Among High School-Aged Adolescents

摘要/项目总结 大麻是美国青少年中仅次于酒精的最常用成瘾物质。青春期 可能是一个独特的发展窗口，在此期间，大麻对认知产生了最深远的影响， 由于大脑中对注意力和执行功能（AEF）至关重要的区域正在不断成熟， 能力集中在学术上的成功和社会功能。然而，存在高度矛盾的发现， 大麻相关的认知缺陷甚至在禁欲的早期持续存在的程度，以及 是否个人层面的因素，重要的是注意力缺陷/多动障碍（ADHD），缓和这些 方面的影响.解决这一知识具有广泛影响的巨大潜力，包括告知医生建议 青少年和他们的父母，以及地方，全州和国家的政策制定。这5年的指导 以病人为导向的研究职业发展奖将检验以下假设：（1）AEF改善缓慢 但是，（2）ADHD的遗传风险可能会使AEF的变化率变钝。我们 建议从波士顿地区的公立高中招募有和没有经常使用大麻的青少年。 符合条件的大麻使用者将被随机分配到应急管理干预， 鼓励4周的大麻戒断，或无戒断要求的非应急监测。所有 参与者（包括非使用者）将完成认知评估、毒理学测试、自我报告 在4周内的7个时间点进行问卷调查和半结构式情绪和物质使用访谈 研究以及1次30天随访。禁欲将通过大麻水平的下降来索引 尿液中的代谢物。分析将检查（1）戒断大麻4周后AEF的差异 使用者、非禁欲者和非使用者;（2）禁欲者中AEF的纵向受试者内变化 大麻使用者;（3）ADHD多基因风险与大麻使用，基线AEF和AEF之间的关联 复苏每个科学目标对应于具体的培训目标，映射到3个领域的能力：（1） 临床试验设计和实施，（2）纵向分析，（3）精神病遗传学，以及 在负责任地开展研究和职业发展方面进行培训。培训目标将得到落实 在A医生的专业指导下Eden Evins（主要导师），Jordan Smoller博士（共同导师）和 由大卫·舍恩菲尔德博士、艾莉莎·道尔博士和罗宾·默梅尔斯坦博士组成的顾问小组。这项研究，结合 随着培训目标的完成，将有效地推动我走向我的长期目标，一个独立的 职业生涯作为一个翻译临床科学家，旨在了解认知风险因素和机制， 青少年大麻使用，以及这些因素和其他因素（例如，遗传学、环境、精神病理学） 影响治疗参与、反应和功能结局。这将为未来几年的发展奠定基础。 影响力大的研究侧重于预防和干预青少年早期使用问题药物。

ABSTRACT/PROJECT SUMMARY Cannabis is the most commonly used addictive substance among U.S. adolescents after alcohol. Adolescence may be a unique developmental window during which cannabis exerts its most profound impact on cognition, due to ongoing maturation in brain regions critical to attention and executive functioning (AEF), cognitive capacities centrally involved in academic success and social functioning. Yet, highly contradictory findings exist on the degree to which cannabis-associated cognitive deficits persist even in the early days of abstinence, and whether individual-level factors, importantly Attention Deficit/Hyperactivity Disorder (ADHD), moderate these effects. Addressing this knowledge has a large potential for broad impact, including informing physician advice to adolescents and their parents, and local, statewide, and national policymaking. This 5-year mentored patient-oriented research career development award will test the hypotheses that (1) AEF improves slowly across 4 weeks of abstinence, but that (2) genetic risk for ADHD may blunt the rate of AEF change. We propose to recruit adolescents with and without regular cannabis use from Boston-area public high schools. Eligible cannabis users will be randomized to either a contingency management intervention which will incentivize 4 weeks of cannabis abstinence, or non-contingent monitoring with no abstinence requirement. All participants (including non-users) will complete cognitive assessments, toxicology testing, self-report questionnaires and semi-structured mood and substance use interviews at 7 time points during the 4 week study as well as 1 30-day follow-up visit. Abstinence will be indexed by decreasing levels of cannabis metabolites in urine. Analyses will examine the (1) differences in AEF after 4 weeks among abstinent cannabis users, non-abstinent users, and non-users; (2) longitudinal, within-subject change in AEF among abstinent cannabis users; and (3) association between ADHD polygenic risk and cannabis use, baseline AEF, and AEF recovery. Each scientific aim corresponds to specific training goals, mapping onto competency in 3 areas: (1) clinical trial design and implementation, (2) longitudinal analysis, and (3) psychiatric genetics, as well as training in the responsible conduct of research and career development. Training goals will be implemented with the expert guidance of Dr. A. Eden Evins (primary mentor), Dr. Jordan Smoller (co-mentor), and the advisory team consisting of Drs. David Schoenfeld, Alysa Doyle, and Robin Mermelstein. This study, coupled with completion of the training goals, will effectively propel me towards my long-term goal of an independent career as a translational clinical scientist aiming to understand the cognitive risk factors and mechanisms of adolescent cannabis use, and how these and other factors (e.g., genetics, environment, psychopathology) affect treatment engagement, response and functional outcomes. This will lay the foundation for several future high-impact studies focused on prevention and intervention of early problem substance use in youth.