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

大麻使用障碍的海马突触密度缺陷在戒断后会改善吗？

基本信息

批准号：
10280518
负责人：
DEEPAK Cyril D'SOUZA
金额：
$ 52.48万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-15 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10280518
关键词：
Abstinence Accounting Adolescence Adolescent Adult Age Animals Auditory Awareness Benefits and Risks Binding Biological Brain Brain imaging Brain region CNR1 gene Cannabinoids Cannabis Chronic Cognition Cognitive deficits DSM-V Data Diagnosis Drug usage Electroencephalography Exposure to Gender Goals Hippocampus (Brain)Human Image Individual Insula of Reil Laws Legal Ligands Link Maze Learning Measures Medial Medical Memory Methods Molecular Monitor Morphology Parahippocampal Gyrus Participant Performance Pharmaceutical Preparations Positron-Emission Tomography Proteins Psychiatry Recovery Reporting Research Resolution Rodent Scanning Societies Specificity Structure Synapses Synaptic Vesicles Task Performances Teenagers Temporal Lobe Testing Tracer Verbal Learning Vertebral column Work density experience gray matter improved in vivo indexing marijuana use marijuana use disorder marijuana user partial recovery receptor downregulation risk perception sex spatial memory synthetic cannabinoid young adult

项目摘要

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.

项目概要和摘要背景：大麻是最常用的药物之一。大麻的“医疗”和娱乐用途在美国越来越合法化。过去十年，青少年对吸食大麻风险的认识有所下降。大麻的使用通常发生在青春期和青年期，此时大脑仍在发育，最容易受到侮辱，尤其是毒品，因此，了解侮辱的后果很重要。长期接触大麻素对大脑结构和功能的影响。我们最近证明，啮齿类动物的大麻素会导致突触密度降低。测量的大麻使用障碍（CUD）参与者的海马突触小泡密度较低使用 [11C]UCB-J（一种正电子发射断层扫描 (PET) 示踪剂）对突触小泡蛋白 SV2A 进行成像 CUD 参与者在海马言语记忆任务和言语记忆方面表现较差。然而，海马的表现与[11C]UCB-J结合是否较低有关。突触密度和记忆能力缺陷是否会随着戒除大麻而恢复正常尚不清楚。本研究的目的是比较禁欲 4 周前后 CUD 中的突触小泡密度大麻使用的影响，并将突触密度的变化与海马功能（语言记忆）联系起来。此外，海马 [11C]UCB-J 结合、言语记忆和言语记忆测量之间的关系将探讨大麻暴露（首次使用年龄和终生暴露）。假设：CUD 将显示海马 [11C]UCB-J 结合和言语记忆的增加在 CUD 参与者中，大麻使用年龄较早，并且在确认戒断 4 周后的表现。大麻的累积暴露与海马 [11C]UCB-J 结合相关。方法：我们将使用禁欲 4 周之前和之后的 CUD 突触小泡密度进行比较 [11C]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，以验证长期测试-重测的稳定性。海马 [11C]UCB-J 结合、言语记忆和大麻暴露测量（开始年龄）之间的关系使用和终生暴露）将在 CUD 中进行探索。试点数据：CUD (n=12) 显示较低的海马 SV2A 和言语记忆，且 CUD (n=2) 相关。显示在确认戒除大麻约 4 周后，[11C]UCB-J 结合增加。