Effect of Cannabis Use on Synaptic Density in Older Adults

项目摘要和摘要 背景：这一新的R21应用是为了检测大麻使用对活体海马区的影响 老年人的突触密度和认知能力(对NOSI(非-DA-20-014)的反应：“大麻， 老年人使用处方阿片类药物或处方苯二氮卓类药物“)。大麻是 最常用和最广泛使用的非法药物；大麻在老年男性和女性中的使用量正在增加 55岁以上和老年人(50岁)是大麻使用增长最快的年龄段； “医用”和娱乐性大麻使用合法化继续在全球蔓延；大麻的效力 一直在稳步上升，大麻使用和大麻使用障碍(CUD)的比率是 越来越多。因此，重要的是要了解长期接触大麻对 老年人的大脑结构和功能。与青少年和年轻人的研究相反，在动物上 研究表明，给成年老年啮齿类动物注射大麻类物质会导致 海马区突触密度和认知功能的改善。现在可以检查突触 用高特异性正电子发射断层扫描(PET)示踪剂[11C]UCB-J体内密度测定 突触囊泡蛋白SV2a。我们最近发现，在患有大麻使用障碍(CUD)的年轻人中， 用[11C]UCB-J结合法(BPND)测定的活体海马区突触小泡密度降低了约10% 而不是健康对照组。此外，年轻的成年CUD参与者在海马区的言语测试中表现更差 记忆任务和言语记忆成绩与海马区[11C]UCB-J结合相关。然而， 吸食大麻的老年人是否在体内改变了海马区突触密度 到目前为止已经检查过了。本研究的目的是比较在体海马突触小泡密度。 大麻--使用老年人，并将体内海马区突触密度的变化与海马区联系起来 功能(语言和空间记忆)。 假设：吸食大麻的老年人(年龄50岁)将表现出海马区[11C]UCB- J结合(BPND)与年龄、性别、体重指数、智商匹配的健康对照组的比较。此外，这一增长 在[11C]中，结合UCB-J将与改善海马体功能(语言和空间记忆)相关。 方法：我们将比较使用大麻的老年人的体内海马区突触密度(年龄50岁， 40岁后首次开始使用大麻)使用[11C]UCB-J正电子发射计算机断层扫描和高分辨率研究 体层摄影术和年龄、性别、体重指数、智商匹配的健康对照(HCS)，并适当考虑性别 一种生物变量。大鼠海马区[11C]UCB-J结合与言语记忆的关系 将探讨大麻暴露的衡量标准(开始使用的年龄和终生暴露)。 影响：据我们所知，这是第一次研究使用大麻对体内的影响 老年人的海马区突触密度。

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.