Changes in cognition and psychiatric disorder symptoms during cannabis abstinence using a novel discordant twin design

使用新颖的不一致双胞胎设计改变大麻戒断期间的认知和精神疾病症状

• 批准号: 10281552
• 负责人: Jessica Megan Ross
• 金额: $ 17.46万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10281552
• 关键词: Abstinence; Adolescence; Adult; Anxiety; Attention; Attention deficit hyperactivity disorder; Back; Behavioral Genetics; Candidate Disease Gene; Cannabis; Clinical Trials; Cognition; Cognition Disorders; Cognitive; Colorado; Control Groups; Controlled Study; Data; Diagnosis; Educational workshop; Environment; Environmental Risk Factor; Genes; Genetic Polymorphism; Genetic Risk; Genotype; Goals; Gold; Health; Household; Impaired cognition; Incentives; Individual; Language; Legal; Life; Maps; Measures; Memory; Mental Depression; Mental disorders; Mentors; Methodology; Methods; Monitor; Monozygotic twins; Motivation; Older Population; Outcome; Participant; Patients; Pattern; Performance; Positioning Attribute; Preparation; Protocols documentation; Public Health; Randomized; Randomized Controlled Trials; Recording of previous events; Recovery; Registries; Reporting; Research; Research Design; Research Personnel; Research Project Grants; Research Training; Resources; Risk; Sample Size; Sampling; Statistical Data Interpretation; Symptoms; Testing; Training; Training Programs; Twin Multiple Birth; Twin Studies; Withdrawal; addiction; base; causal model; cognitive function; cognitive recovery; contingency management; design; epidemiology study; executive function; gene environment interaction; genome wide association study; genome-wide; marijuana use; marijuana user; meetings; memory process; novel; physical conditioning; processing speed; prospective; psychiatric symptom; recruit; research study; responsible research conduct; skills; unethical

PROJECT SUMMARY/ABSTRACT Changes in the legal landscape of cannabis have occurred simultaneously with increases in use among adults. Research efforts have focused on examining consequences of use, however, characterizing the impact of cannabis abstinence on health among regular cannabis users is also a relevant public health concern. Few research studies have compared cognition or psychiatric disorder symptoms between abstinent cannabis users, using contingency management (CM), to individuals in a control condition (monitoring), which does not require changes in cannabis use. The current study aims to extend the findings to an older population, for a longer period of cannabis abstinence, and to examine all cognitive domains. Thus, the first aim is to test the impact of cannabis abstinence for 6 weeks (42 days) on memory, attention, processing speed, language, and executive function (EFs) on adults, who are between 31 to 47 years old. The second aim is to explore how cannabis abstinence effects psychiatric disorder symptoms. The third aim (exploratory) is to examine how genetic risk for various psychiatric disorder symptoms by environment (cannabis abstinence versus continued use) interactions impact cognition. The proposed study is novel in that we will use experimental manipulation to create discordance in cannabis use among monozygotic (MZ) twin pairs. This research design will require significantly fewer resources than large-scale randomized controlled trials because the use of MZ twin pairs requires a smaller sample size and is still sufficiently powered to detect small effects. Fifty identical twin pairs (N=100), who are concordant on cannabis use, will be recruited from the Colorado Twin Registry, which have all been genotyped. Each twin, within a twin pair, will be randomly assigned to either CM, incentive-based protocol to promote abstinence, or control, no changes in cannabis use requested, for 42 days. Participants will be assessed across 42 days on measures of cognition and psychiatric disorder symptoms (baseline, day 14, day 28, and day 42). The method proposed in this project could be used to understand other outcomes from cannabis abstinence (e.g., physical health) or abstinence from other substances. The aims of the research project map on to the training goals: 1) clinical trial methodology, 2) longitudinal statistical analysis, and 3) behavioral genetics. Experts in clinical trial methodology, longitudinal statistical analysis, and behavioral genetics, will guide the research and training program. The team of researchers consists of Drs. John Hewitt and Christian Hopfer (primary mentors, training aim 3), Drs. Susan Mikulich-Gilbertson (mentor, training aim 2) and Naomi Friedman (consultant, training aim 2), Drs. Randi Schuster (co-mentor, training aim 1), Paula Riggs, and Kent Hutchison (consultants, training aim 1). Each training aim consists of one-on-one meetings with mentors or consultants, workshops, courses, seminars, specific analytic projects, responsible conduct of research training and preparation and submission of an R01 application in the final years. Completion of these research and training aims will provide me with the necessary skills to conduct recovery studies and provide preliminary data for an R01 application.

项目概要/摘要 大麻法律格局的变化与大麻使用量的增加同时发生 成年人。研究工作的重点是检查使用的后果，但描述其影响 经常吸食大麻的人戒除大麻对健康的影响也是一个相关的公共卫生问题。很少 研究比较了戒断大麻使用者之间的认知或精神障碍症状， 使用应急管理（CM），对处于控制状态（监控）的个人进行管理，这不需要 大麻使用的变化。目前的研究旨在将研究结果扩展到老年人群，并持续更长的时间 大麻禁欲，并检查所有认知领域。因此，首要目标是测试大麻的影响 禁欲 6 周（42 天）对记忆力、注意力、处理速度、语言和执行功能的影响 (EF) 针对 31 至 47 岁之间的成年人。第二个目标是探讨如何戒除大麻 影响精神障碍症状。第三个目标（探索性）是研究各种遗传风险如何 不同环境（大麻戒断与持续使用）的精神疾病症状相互作用影响 认识。拟议的研究是新颖的，因为我们将使用实验操纵来制造不一致 同卵 (MZ) 双胞胎中使用大麻。该研究设计将需要更少的资源 优于大规模随机对照试验，因为使用同卵双胞胎需要较小的样本量 并且仍然有足够的功率来检测微小的影响。五十对同卵双胞胎 (N=100)，他们在 大麻使用者将从科罗拉多双胞胎登记处招募，这些登记都已进行基因分型。每对双胞胎， 在双胞胎中，将被随机分配到 CM（基于激励的协议以促进禁欲），或 控制，42 天内不要求改变大麻使用情况。参与者将在 42 天内接受评估 认知和精神障碍症状的测量（基线、第 14 天、第 28 天和第 42 天）。方法 该项目中提出的建议可用于了解大麻戒断的其他结果（例如，身体 健康）或戒除其他物质。研究项目的目标映射到培训目标：1) 临床试验方法，2) 纵向统计分析，3) 行为遗传学。临床试验专家 方法论、纵向统计分析和行为遗传学将指导研究和培训 程序。研究团队由博士组成。约翰·休伊特 (John Hewitt) 和克里斯蒂安·霍普弗 (Christian Hopfer)（主要导师、培训 目标3），博士。 Susan Mikulich-Gilbertson（导师，培训目标 2）和 Naomi Friedman（顾问，培训目标 2），博士。 Randi Schuster（联合导师，培训目标 1）、Paula Riggs 和 Kent Hutchison（顾问，培训目标 1）。每个培训目标都包括与导师或顾问的一对一会议、研讨会、课程、 研讨会、具体分析项目、负责任地进行研究培训以及准备和提交 最后几年的 R01 申请。完成这些研究和培训目标将为我提供 进行恢复研究并为 R01 申请提供初步数据的必要技能。