Cognitive Recovery With Cannabis Abstinence Among High School-Aged Adolescents

高中青少年戒除大麻后的认知恢复

• 批准号: 10094208
• 负责人: Randi Melissa Schuster
• 金额: $ 20.06万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2023-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10094208
• 关键词: Abstinence; Address; Adolescence; Adolescent; Adverse effects; Advisory Committees; Affect; Alcohols; Area; Attention; Attention deficit hyperactivity disorder; Behavioral; Boston; Brain region; Cannabis; Characteristics; Clinical; Clinical Research; Clinical Trials; Clinical Trials Design; Cognition; Cognitive; Cognitive deficits; Competence; Coupled; Data; Data Analyses; Development; Development Plans; Early Intervention; Enrollment; Environment; Executive Dysfunction; Exposure to; Foundations; Future; Genetic; Genetic Risk; Goals; Incentives; Individual; Intervention; Interview; Jordan; Knowledge; Learning; Legal; Measures; Medical; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodology; Monitor; Moods; Parents; Participant; Patient Self-Report; Performance; Phenotype; Physicians; Population; Prevalence; Prevention; Psychopathology; Public Health Schools; Questionnaires; Randomized; Recovery of Function; Reporting; Research; Research Project Grants; Risk; Risk Factors; Robin bird; Sampling; School-Age Population; Scientist; Secondary to; Severities; Social Functioning; Stratification; Structure; Subgroup; Testing; Time; Toxicology; Training; Urine; Visit; Youth; addiction; base; career; career development; cognitive capacity; cognitive function; cognitive recovery; cognitive testing; comorbidity; contingency management; design; disorder risk; evidence base; evidence based guidelines; executive function; experience; financial incentive; follow-up; functional improvement; functional outcomes; genetic variant; high risk; high school; improved; improved functioning; indexing; longitudinal analysis; marijuana use; marijuana user; neurobiological mechanism; patient oriented; polygenic risk score; prospective; psychogenetics; recruit; research and development; response; responsible research conduct; secondary outcome; substance use; success; tool

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.

摘要/项目摘要 大麻是酒精后美国青少年中最常用的成瘾物质。青春期 可能是一个独特的发展窗口，在此窗口中，大麻对认知最深远的影响， 由于在关注和执行功能至关重要的大脑区域中持续成熟（AEF），认知能力 能力集中参与学术成功和社会功能。但是，存在高度矛盾的发现 即使在禁欲的早期，与大麻相关的认知缺陷持续存在的程度以及 个人级别因素，重要的是注意力缺陷/多动症（ADHD）是否适应这些 效果。解决这一知识具有广泛影响的潜力，包括通知医师建议 对于青少年及其父母以及当地，全州和国家决策。这项为期5年的指导 以患者为导向的研究职业发展奖将检验（1）AEF缓慢改善的假设 在禁欲的4周中，但是（2）ADHD的遗传风险可能会钝化AEF的变化率。我们 建议在波士顿地区公立高中招募有或没有定期使用大麻的青少年。 符合条件的大麻用户将被随机分配到应急管理干预措施中 激励4周的大麻禁欲或无戒酒的监测，而无需禁欲。全部 参与者（包括非用户）将完成认知评估，毒理学测试，自我报告 问卷和半结构化的情绪和物质使用访谈在4周内的7个时间点 学习以及1 30天的随访访问。大麻水平降低，节制将被索引 尿液中的代谢产物。分析将检查戒断大麻4周后AEF的（1）差异 用户，非属于用户和非用户； （2）戒酒中的纵向，主题内的AEF内变化 大麻使用者； （3）ADHD多基因风险与使用大麻，基线AEF和AEF之间的关联 恢复。每个科学目标都对应于特定的培训目标，并将3个领域的能力映射到：（1） 临床试验设计和实施，（2）纵向分析和（3）精神遗传学以及 负责研究和职业发展的培训。将实施培训目标 在A. Eden Evins博士（主要导师），Jordan Smoller博士（Co-Incertor）和The The的专家指导下 由DRS组成的咨询团队。 David Schoenfeld，Alysa Doyle和Robin Mermelstein。这项研究，耦合 随着培训目标的完成，将有效地推动我实现独立的长期目标 职业作为转化临床科学家，旨在了解认知风险因素和机制 青少年大麻的使用，以及这些因素和其他因素（例如遗传学，环境，心理病理学） 影响治疗参与，反应和功能结果。这将为几个未来奠定基础 高影响力的研究集中于预防和干预青年早期问题的使用。