Do hippocampal synaptic density deficits in cannabis use disorder improve following abstinence?

项目总结和摘要 背景：大麻是全球最常用的毒品之一。大麻的功效 大麻的“医疗”和娱乐用途在美国越来越合法化。 在过去十年中，青少年对大麻使用风险的认识有所下降。启动 大麻的使用通常发生在青春期和成年初期，当时大脑仍在发育， 最容易受到侮辱，尤其是毒品。因此，重要的是要了解的后果， 慢性大麻素暴露对大脑结构和功能的影响。重复给予 大麻素对啮齿类动物的作用已显示导致较低的突触密度。最近，我们发现， 大麻使用障碍（CUD）参与者海马中较低的突触囊泡密度， 使用[11 C]UCB-J，一种用于突触囊泡蛋白SV 2A成像的正电子发射断层扫描（PET）示踪剂 in vivo. CUD参与者在海马非文字记忆任务中表现较差， 性能与海马[11 C]UCB-J结合相关。然而，海马下部是否 突触密度和记忆表现缺陷在大麻使用戒断后正常化是未知的。 本研究的目的是比较戒断4周前后CUDs中的突触囊泡密度 从大麻的使用，并与突触密度的变化海马功能（文字记忆）。 此外，海马[11 C]UCB-J结合，文字记忆和测量之间的关系， 将探讨大麻接触情况（首次使用年龄和终生接触）。 假设：CUD将显示海马[11 C]UCB-J结合和言语记忆增加 在确认禁欲4周后的表现。在CUD参与者中，大麻使用年龄较早， 累积暴露于大麻将与海马[11 C]UCB-J结合相关。 方法：采用免疫组化方法，比较戒断4周前后CUDs中突触囊泡密度的变化。 [11 C]UCB-J PET和高分辨率研究断层扫描仪。年龄、性别匹配的健康对照（HC） 还将在基线和4周时进行扫描，以验证长期的重测稳定性。的关系 海马[11 C]UCB-J结合、文字记忆和大麻暴露测量（开始使用的年龄）之间 使用和终生暴露）将在CUD中进行探索。 初步数据：CUD（n=12）显示较低的海马SV 2A和言语记忆，这是相关的。CUD（n=2） 显示[11 C]UCB-J结合增加，证实戒断大麻约4周。

PROJECT SUMMARY AND ABSTRACT Background: Cannabis is amongst the most commonly used drugs globally. The potency of cannabis has increased, and the “medical” and recreational use of cannabis is increasingly being legalized across the U.S. Perceptions of the risks of cannabis use amongst teenagers have 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 rodents has been shown to result in lower synaptic density. Consistently, we recently showed lower synaptic vesicle density in the hippocampus in cannabis use disorder (CUD) participants as measured using [11C]UCB-J, a positron emission tomography (PET) tracer for imaging of the synaptic vesicle protein SV2A in vivo. CUD participants performed worse on a hippocampal verbal memory task, and verbal memory performance correlated with hippocampal [11C]UCB-J binding. However, whether the lower hippocampal synaptic density and deficits in memory performance normalize with abstinence from cannabis use is not known. The purpose of this study is to compare synaptic vesicle density in CUDs before and after 4 weeks of abstinence from cannabis use, and to relate changes in synaptic density to hippocampal function (verbal memory). Furthermore, the relationship between hippocampal [11C]UCB-J binding, verbal memory, and measures of cannabis exposure (age of first use and lifetime exposure) will be explored. Hypotheses: CUDs will show an increase in both hippocampal [11C]UCB-J binding, and verbal memory performance following 4 weeks of confirmed abstinence. In CUD participants, earlier age of cannabis use and cumulative exposure to cannabis will be correlated to hippocampal [11C]UCB-J binding. Methods: We will compare synaptic vesicle density in CUDs before and after 4 weeks of abstinence using [11C]UCB-J PET and the High Resolution Research Tomograph. Age-, gender matched healthy controls (HCs) will also be scanned at baseline and at 4 weeks in order to verify longer-term test-retest stability. 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 in CUDs. Pilot data: CUDs (n=12) show lower hippocampal SV2A and verbal memory, which are correlated. CUDs (n=2) show an increase in [11C]UCB-J binding with confirmed abstinence from cannabis for ~4 weeks.