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 大麻是美国青少年中仅次于酒精的最常用的成瘾物质。青春期 可能是一个独特的发展窗口，在此期间大麻对认知产生最深刻的影响， 由于大脑对注意力和执行功能(AEF)至关重要的区域正在不断成熟，认知 在学术成就和社会功能方面发挥核心作用的能力。然而，存在着高度矛盾的发现。 即使在戒烟的早期，与大麻相关的认知缺陷仍然存在的程度，以及 个人层面的因素，尤其是注意力缺陷/多动障碍(ADHD)，是否会缓和这些 效果。解决这一知识具有广泛影响的巨大潜力，包括向医生提供建议 对青少年及其父母，以及地方、全州和国家的政策制定。这位为期5年的导师 以患者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(2)ADHD的遗传风险可能会降低AEF的变化率。我们 建议从波士顿地区的公立高中招收经常使用大麻和不经常使用大麻的青少年。 符合条件的大麻使用者将随机接受应急管理干预，该干预将 鼓励4周的大麻戒断，或不要求戒烟的非应急监测。全 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化情绪和物质使用访谈 并进行为期30天的随访。禁欲将以大麻水平的下降为指标 尿液中的代谢物。分析将检验(1)戒除大麻4周后AEF的差异 使用者、非禁欲使用者和非禁欲使用者；(2)禁欲者中AEF的纵向、受试者内变化 大麻使用者；和(3)ADHD多基因风险与大麻使用、基线AEF和AEF之间的关联 恢复。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)精神病学遗传学，以及 负责任地进行研究和职业发展方面的培训。将落实培训目标 在A·伊登·埃文斯博士(主要导师)、乔丹·斯莫勒博士(共同导师)和 由大卫·舍恩菲尔德博士、阿莉莎·道尔博士和罗宾·梅梅尔斯坦博士组成的顾问团队。这项研究，加上 随着培训目标的完成，将有力地推动我朝着我的长期目标独立 转化型临床科学家的职业生涯，旨在了解认知风险因素和机制 青少年使用大麻，以及这些因素和其他因素(例如，遗传、环境、精神病理学)如何 影响治疗参与度、反应和功能结果。这将为未来几年奠定基础 高影响力的研究侧重于预防和干预青少年早期使用问题物质。