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

项目摘要和摘要 背景：大麻是全球最常用的毒品之一。大麻的效力有 在美国，大麻的“医疗”和娱乐用途日益合法化。 在过去的十年里，青少年对大麻使用风险的看法有所下降。入会仪式 大麻的使用通常发生在青春期和青春期，当时大脑仍在发育中， 最容易受到侮辱，尤其是毒品。因此，重要的是要了解 长期接触大麻素对大脑结构和功能的影响。反复给药 大麻素对啮齿动物的作用已被证明会导致较低的突触密度。始终如一地，我们最近展示了 大麻使用障碍(CUD)参与者海马区突触小泡密度降低 用[11C]UCB-J，正电子发射断层扫描(PET)示踪剂对突触囊泡蛋白SV2a进行成像 在活体内。CUD参与者在海马区的言语记忆任务中表现较差，而言语记忆 表现与海马区[11C]UCB-J结合有关。然而，无论下部海马区 随着大麻使用的戒断，突触密度和记忆性能缺陷会正常化，这一点尚不清楚。 本研究的目的是比较戒酒4周前后CUD患者的突触小泡密度。 从大麻的使用，并将突触密度的变化与海马体功能(言语记忆)联系起来。 此外，还研究了海马区[11C]UCB-J结合与言语记忆和记忆测量的关系。 将探讨大麻暴露(首次使用年龄和终生暴露)。 假设：CUDS将表现出海马区[11C]UCB-J结合和言语记忆的增加 在确认戒酒4周后的表现。在戒毒治疗参与者中，较早的大麻使用年龄和 累积大麻暴露将与海马区[11C]UCB-J结合相关。 方法：比较戒酒4周前后CUDS大鼠突触小泡密度。 [11C]UCB-J正电子发射计算机断层扫描和高分辨率研究断层摄影。年龄、性别匹配的健康对照(HCS) 也将在基线和4周时进行扫描，以验证较长期的测试-重测稳定性。两国关系 在海马区[11C]UCB-J结合、言语记忆和大麻暴露措施之间(开始年龄 使用和终生暴露)将在CUD中进行探索。 实验数据：CUDS(n=12)表现出较低的海马区SV2a和言语记忆，这两者是相关的。CUDS(n=2) 证实戒除大麻约4周后，[11C]UCB-J结合量增加。

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.