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: 10493421
• 负责人: Rajiv Radhakrishnan
• 金额: $ 20.94万
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10493421
• 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.

项目摘要和摘要 背景：此新的R21应用程序是检查使用大麻对体内海马的影响 老年人的突触密度和认知（响应NOSI（非DA-20-014）：“大麻， 老年人处方阿片类药物或处方苯二氮卓类药物使用”）。大麻是一种 最常用和广泛使用的非法药物；大麻使用的男性和女性正在增加 超过55岁，老年人（> 50岁）代表了使用最快的大麻年龄段；这 “医疗”和娱乐大麻使用的合法化在全球范围内继续传播；大麻的效力 一直在悄悄地增加，大麻使用和大麻使用障碍（CUD）的发生率是 增加。因此，重要的是要了解慢性大麻暴露对 老年人的大脑结构和功能。与青少年和年轻人的研究相反 研究，已经证明将大麻素施用给老年啮齿动物会导致增加 海马突触密度和改善的认知功能。现在可以检查突触 使用[11C] UCB-J，一个极性发射断层扫描（PET）示踪剂，具有很高特异性的体内密度 突触囊泡蛋白SV2A。我们最近表明，在大麻使用障碍（CUD）的年轻人中， 通过[11C] UCB-J结合（BPND）测量的体内海马突触囊泡密度低约10％ 而不是健康的对照。此外，年轻的成年人cud参与者在海马语言上表现较差 内存任务和语言记忆性能与海马[11C] UCB-J绑定相关。然而， 使用大麻的老年人是否改变了体内海马突触密度 检查了至今。这项研究的目的是比较体内海马突触囊泡密度 使用大麻的老年人，并将体内海马突触密度变化与海马 功能（言语和空间记忆）。 假设：吸用大麻的老年人（> 50岁）将表明海马[11C] UCB-- 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 在[11C]中，UCB-J结合将与改善的海马功能（言语和空间记忆）有关。 方法：我们将比较使用大麻的老年人体内海马突触密度（年龄> 50岁， 使用[11C] UCB-J PET和高分辨率研究 断层片和年龄，性别，BMI-，IQ匹配的健康对照（HCS），并适当考虑性 生物变量。海马[11C] UCB-J结合，口头记忆和 将探讨大麻暴露的度量（使用年龄和终生暴露年龄）。 影响：据我们所知，这是研究大麻使用对体内影响的第一项研究 老年人的海马突触密度。