Effect of Cannabis Use on Synaptic Density in Older Adults

项目总结和摘要 背景：这项新的R21应用是为了检查大麻使用对体内海马神经元的影响。 老年人中的突触密度和认知（响应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 最常见和最广泛使用的非法药物;大麻的使用在年龄较大的男性和女性中正在增加 55岁以上，老年人（年龄> 50岁）是增长最快的大麻使用年龄组; “医疗”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 增加。因此，重要的是要了解慢性大麻暴露的后果， 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，向老年啮齿动物施用大麻素会导致增加 海马突触密度和改善认知功能。现在可以检查突触 使用[11 C]UCB-J进行体内密度测定，[11 C]UCB-J是一种具有高度特异性的正电子发射断层扫描（PET）示踪剂， 突触囊泡蛋白SV 2A。我们最近发现，在患有大麻使用障碍（CUD）的年轻人中， 通过[11 C] UCB-J结合（BPND）测量的体内海马突触囊泡密度降低约10 比健康的对照组。此外，年轻的成年CUD参与者在海马语言上的表现更差， 记忆任务和言语记忆表现与海马[11 C]UCB-J结合相关。然而，在这方面， 使用大麻的老年人是否改变了体内海马突触密度， 检查至今。本研究的目的是比较在体海马突触囊泡密度， 使用大麻的老年人，并将体内海马突触密度的变化与海马 功能（言语和空间记忆）。 假设：使用大麻的老年人（年龄> 50岁）将表现出海马[11 C]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，这一增长 [11 C]UCB-J结合与海马功能（语言和空间记忆）改善相关。 方法：我们将比较使用大麻的老年人（年龄> 50岁， 40岁后首次使用大麻）使用[11 C]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），适当考虑性别， 一个生物变量海马[11 C]UCB-J结合、文字记忆和 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，以检查大麻使用对体内 老年人海马突触密度。

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.