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

项目摘要/摘要 在大麻使用增加的同时，大麻的法律格局也发生了变化。 成年人。然而，研究工作的重点是检查使用的后果，描述其影响 经常吸食大麻的人的大麻戒断对健康的影响也是一个相关的公共卫生问题。一些 研究比较了戒毒大麻使用者的认知或精神障碍症状， 使用应急管理(CM)，对处于控制条件(监控)的个人，这不需要 大麻使用的变化。目前的研究旨在更长时间内将这一发现推广到老年人口。 对大麻戒断情况进行评估，并检查所有认知领域。因此，第一个目标是测试大麻的影响。 禁食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 (EFS)适用于31至47岁的成年人。第二个目标是探索大麻戒断是如何 影响精神障碍症状。第三个目标(探索性的)是检查不同的遗传风险 按环境划分的精神障碍症状(大麻戒除与持续使用)相互作用的影响 认知力。这项拟议的研究是新颖的，因为我们将使用实验操作来制造不一致 在同卵双胞胎(MZ)中使用大麻。这项研究设计需要的资源将大大减少 与大规模随机对照试验相比，这是因为使用MZ双胞胎对需要较小的样本量 仍然有足够的能量来探测微小的影响。50对同卵双胞胎(N=100)，他们在 大麻使用，将从科罗拉多州双胞胎登记处招募，这些人都已进行了基因分型。每一个双胞胎， 在一对双胞胎中，将被随机分配到CM，基于激励的协议以促进禁欲，或 对照，42天内不要求改变大麻的使用。参与者将在42天内接受评估 测量认知和精神障碍症状(基线、第14天、第28天和第42天)。方法 本项目中提出的建议可用于理解大麻戒断的其他结果(例如，物理 健康)或戒除其他物质。研究项目的目标与培训目标相一致：1) 临床试验方法学，2)纵向统计分析，3)行为遗传学。临床试验中的专家 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John Hewitt博士和Christian Hopfer博士(主要导师，培训)组成 目标3)、苏珊·米库里奇-吉尔伯森博士(导师，培训目标2)和娜奥米·弗里德曼(顾问，培训目标 2)、兰迪·舒斯特博士(共同导师，培训目标1)、保拉·里格斯和肯特·哈奇森(顾问，培训目标1) 1)。每个培训目标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、负责任地开展研究培训、准备和提交 在最后几年申请R01。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应用程序提供初步数据所需的技能。

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.