Synaptic Vesicle Density in Cannabis Dependence

项目摘要和摘要 背景：大麻是年轻人最常使用的非法药物。大麻的效力有 使用高效合成大麻素(“香料”)的情况也有所增加。此外，“医疗”和 娱乐使用大麻在美国越来越合法化。 对风险的认知 青少年中的大麻使用情况 在过去的十年里下降了 。开始使用大麻通常 发生在青春期和青壮年，此时大脑仍在发育，最容易患上 侮辱，尤其是毒品。因此，重要的是要了解慢性大麻素的后果。 暴露在大脑的结构和功能上。反复给两种啮齿动物注射大麻类物质 已经被证明可以降低突触密度，但这还没有在人类身上进行研究。我们最近开发了 [11C]-UCB-J，体内突触囊泡蛋白SV2A的示踪剂。这一探索性的目的 研究旨在比较大麻依赖受试者(CD)和健康对照组(HCS)的突触密度，并 突触密度的变化与大脑活动的近端和远端测量有关，即诱发的ɣ 脑电和言语记忆的振荡。此外，[11C]-UCB-J结合与[11C]-UCB-J结合， 诱发的ɣ振荡、言语记忆和大麻暴露的测量(首次使用年龄和终生 曝光率)将被探索。 假设：与Hcs相比，CDs将表现出1)↓[11C]-Ucb-J结合，2)↑在诱发ɣ测量中的缺陷 3)言语记忆中的↑缺陷。在CD受试者中，较低的[11C]UCB-J结合将是正的 与较早开始使用大麻的年龄、终生接触大麻、言语记忆较差和 ɣ振荡中的更大赤字。 方法：我们将比较CDS(n=12)和HCS(n=12)的突触密度。 [11C]- UCB-J和HIGH 分辨率研究断层摄影术。CDS和HCS还将在诱发ɣ振荡的测量方面进行比较 (听觉稳态反应：ASSR)和言语记忆(Rey听觉词语学习任务：RAVLT)。这个 两者之间的关系 [11C]- Ucb-J结合、诱发的ɣ振荡、言语记忆和大麻测量 将探讨暴露(开始使用的年龄和终生暴露)。 试点数据：为了证明可行性，研究了CDS(n=2)和HC(n=6)；CDS显示减少 在几个大脑区域中，SV2A结合10%或更多(即，大于重测变异性的边际)。

PROJECT SUMMARY AND ABSTRACT Background: Cannabis is the most commonly used illicit drug by young people. The potency of cannabis has increased and so has the use of highly potent synthetic cannabinoids (`Spice'). Furthermore, the “medical” and recreational use of cannabis is increasingly being legalized across the U.S. Perceptions of the risks of cannabis use amongst teenagers has declined over the past decade . The initiation of cannabis use typically occurs during adolescence and young adulthood, when the brain is still developing and is most vulnerable to insults, particularly drugs. Therefore, it is important to understand the consequences of chronic cannabinoid exposure on the structure and function of the brain. Repeated administration of cannabinoids to both rodents has been shown to lower synaptic density, but this has yet to be studies in humans. We recently developed [11C]-UCB-J, a tracer for imaging of the synaptic vesicle protein SV2A in vivo. The purpose of this exploratory study is to compare synaptic density in cannabis dependent subjects (CDs) and healthy controls (HCs) and to relate changes in synaptic density to proximal and distal measures of brain activity, namely evoked ɣ oscillations in the EEG and verbal memory. Furthermore, the relationship between [11C]-UCB-J binding, evoked ɣ oscillations, verbal memory, and measures of cannabis exposure (age of first use and lifetime exposure) will be explored. Hypotheses: Compared to HCs, CDs will show 1) ↓ [11C]-UCB-J binding, 2) ↑ deficits in measures of evoked ɣ oscillations, and 3) ↑ deficits in verbal memory. In CD subjects, lower [11C]UCB-J binding will be positively correlated with earlier age of initiation of cannabis use, lifetime cannabis exposure, worse verbal memory and greater deficits in ɣ oscillations. Methods: We will compare synaptic density in CDs (n=12) vs. HCs (n=12) using [11C]- UCB-J and the High Resolution Research Tomograph. CDs and HCs will also be compared on measures of evoked ɣ oscillations (auditory steady state response: ASSR) and verbal memory (Rey Auditory Verbal Learning Task: RAVLT). The relationship between [11C]- UCB-J binding, evoked ɣ oscillations, verbal memory, and measures of cannabis exposure (age of initiation of use and lifetime exposure) will be explored. Pilot data: To demonstrate feasibility, CDs (n=2) and HC (n=6) have been studied; CDs showed reduced SV2A binding of 10% or more (i.e., greater than the margin of test-retest variability) in several brain regions.