Effect of Cannabis Use on Synaptic Density in Older Adults

大麻使用对老年人突触密度的影响

• 批准号: 10294727
• 负责人: Rajiv Radhakrishnan
• 金额: $ 25.13万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10294727
• 关键词: Accounting; Adolescent and Young Adult; Age; Agonist; Alzheimer' s Disease; Animals; Attention; Auditory; Behavioral; Benzodiazepines; Binding; Biological; Body mass index; Brain; Brain imaging; Brain region; CNR1 gene; Cannabinoids; Cannabis; Chronic; Cognition; DSM-V; Data; Dose; Drug usage; Elderly; Exposure to; Female; Gender; Goals; Hippocampus (Brain); Human; Individual; Insula of Reil; Learning; Legal; Ligands; Maze Learning; Measures; Medial; Medical; Memory; Methods; Molecular; Morphology; Mus; Neurobiology; Neurocognitive Deficit; Parahippocampal Gyrus; Participant; Performance; Phenotype; Positron-Emission Tomography; Proteins; Psychiatry; Publishing; Reporting; Research; Resolution; Rodent; Specificity; Structure; Synapses; Synapsins; Synaptic Vesicles; Synaptophysin; Task Performances; Temporal Lobe; Tetrahydrocannabinol; Tracer; Transgenic Organisms; Verbal Learning; Vertebral column; Work; age group; cognitive function; cognitive performance; cognitive testing; cohort; density; gray matter; illicit drug use; improved; in vivo; juvenile animal; marijuana use; marijuana use disorder; marijuana user; mature animal; men; older women; performance tests; prescription opioid; protein biomarkers; radiotracer; response; sex; spatial memory; synaptogenesis; synthetic cannabinoid; young adult

PROJECT SUMMARY AND ABSTRACT Background: This new R21 application is to examine the effects of cannabis use on in vivo hippocampal synaptic density and cognition among older adults (in response to NOSI (NOT-DA-20-014): “Cannabis, Prescription Opioid, or Prescription Benzodiazepine Drug Use Among Older Adults”). Cannabis is one of the most commonly and widely used illicit drugs; cannabis use is increasing among men and women older than 55 years, and older adults (age>50yrs) represent the fastest growing cannabis-using age group; the legalization of “medical” and recreational cannabis use continues to spread globally; the potency of cannabis has been steadily increasing, and the rates of cannabis use and cannabis use disorder (CUD) are increasing. Therefore, it is important to understand the consequences of chronic cannabis exposure on brain structure and function in older adults. Contrary to studies in adolescents and young adults, in animal studies, administration of cannabinoids to older adult rodents has been shown to result in increased hippocampal synaptic density and improved cognitive function. It is now possible to examine synaptic density in vivo using [11C]UCB-J, a positron emission tomography (PET) tracer with high specificity for synaptic vesicle protein SV2A. We recently showed that in young adults with cannabis use disorder (CUD), in vivo hippocampal synaptic vesicle density, as measured by [11C] UCB-J binding (BPND), was ~10% lower than healthy controls. Additionally, young adult CUD participants performed worse on a hippocampal verbal memory task, and verbal memory performance correlated with hippocampal [11C]UCB-J binding. However, whether cannabis-using older adults have altered in vivo hippocampal synaptic density has not been examined to-date. The purpose of this study is to compare in vivo hippocampal synaptic vesicle density in cannabis-using older adults, and to relate changes in in vivo hippocampal synaptic density to hippocampal function (verbal and spatial memory). Hypotheses: Cannabis-using older adults (age>50yrs) will demonstrate increased hippocampal [11C]UCB- J binding (BPND) compared to age-, gender-, BMI-, IQ-matched healthy controls. Furthermore, this increase in [11C]UCB-J binding will be associated with improved hippocampal function (verbal and spatial memory). Methods: We will compare in vivo hippocampal synaptic density in cannabis-using older adults (age >50yrs, first initiation of cannabis use after age 40yrs) using [11C]UCB-J PET and the High Resolution Research Tomograph and age-, gender-, BMI-, IQ-matched healthy controls (HCs) with due consideration for sex as a biological variable. The relationship between hippocampal [11C]UCB-J binding, verbal memory, and measures of cannabis exposure (age of initiation of use and lifetime exposure) will be explored. Impact: This is the first study, to our knowledge, to examine the effects of cannabis use on in vivo hippocampal synaptic density in older adults.

项目概要和摘要 背景：这个新的 R21 应用是为了检查大麻使用对体内海马的影响 老年人的突触密度和认知（回应 NOSI (NOT-DA-20-014)：“大麻、 处方阿片类药物或处方苯二氮卓类药物在老年人中的使用”）。大麻是其中之一 最常用和最广泛使用的非法药物；老年男性和女性的大麻使用量正在增加 55 岁以上，老年人（年龄>50 岁）是大麻使用增长最快的年龄组；这 “医疗”和娱乐大麻使用合法化继续在全球蔓延；大麻的效力 大麻使用率和大麻使用障碍（CUD）的比例一直在稳步上升 增加。因此，了解长期接触大麻对人体的影响非常重要。 老年人的大脑结构和功能。与青少年和年轻人的研究相反，在动物中 研究表明，对老年啮齿动物施用大麻素已被证明会导致 海马突触密度和认知功能改善。现在可以检查突触 使用 [11C]UCB-J 进行体内密度测量，[11C]UCB-J 是一种正电子发射断层扫描 (PET) 示踪剂，具有高特异性 突触小泡蛋白SV2A。我们最近表明，在患有大麻使用障碍（CUD）的年轻人中， 通过 [11C] UCB-J 结合 (BPND) 测量，体内海马突触小泡密度降低约 10% 比健康对照。此外，年轻的 CUD 参与者在海马语言方面表现较差 记忆任务和言语记忆表现与海马 [11C]UCB-J 结合相关。然而， 使用大麻的老年人是否改变了体内海马突触密度尚未得到证实 迄今为止已检查过。本研究的目的是比较体内海马突触小泡密度 使用大麻的老年人，并将体内海马突触密度的变化与海马联系起来 功能（语言和空间记忆）。 假设：使用大麻的老年人（年龄 > 50 岁）将表现出海马 [11C]UCB- 增加 J 结合 (BPND) 与年龄、性别、BMI、IQ 匹配的健康对照相比。此外，这种增加 [11C]UCB-J 结合将与改善海马功能（语言和空间记忆）相关。 方法：我们将比较使用大麻的老年人（年龄 > 50 岁， 40 岁后首次开始使用大麻）使用 [11C]UCB-J PET 和高分辨率研究 断层扫描和年龄、性别、BMI、IQ 匹配的健康对照 (HC)，并适当考虑性别 一个生物变量。海马[11C]UCB-J结合、言语记忆和言语记忆之间的关系 将探讨大麻接触的衡量标准（开始使用的年龄和终生接触）。 影响：据我们所知，这是第一项研究大麻使用对体内的影响 老年人海马突触密度。