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？

• 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
• 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

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.

项目摘要和摘要 背景：大麻是全球最常用的药物之一。大麻的效力 在美国，大麻的“医疗”和娱乐使用大麻正在越来越合法化 在过去的十年中，对青少年使用大麻的风险的看法有所下降。倡议 大麻的使用通常发生在青少年和成年期间，当时大脑仍在发育和 最容易受到侮辱，尤其是药物。因此，重要的是要了解 大脑的慢性大麻素暴露于大脑的结构和功能。重复给药 已经显示出对啮齿动物的大麻素会导致突触密度较低。一贯，我们最近显示 如测量 使用[11C] UCB-J，一种极性发射断层扫描（PET）示踪剂进行合成囊泡蛋白SV2A的成像 体内。 CUD参与者在海马语言记忆任务和口头记忆中表现较差 性能与海马[11C] UCB-J结合相关。但是，是否海马 突触密度并在记忆性能中定义，随着使用大麻的禁欲而归一化。 这项研究的目的是比较禁欲4周之前和之后的CUD中的突触囊泡密度 从大麻使用，并将突触密度的变化与海马功能（言语记忆）联系起来。 此外，海马[11C] UCB-J结合，言语记忆和测量 将探索大麻暴露（首次使用和终生暴露年龄）。 假设：CUDS将显示海马[11C] UCB-J结合和口头记忆的增加 确认禁欲4周后的表现。在CUD参与者中，大麻使用年龄和 大麻的累积暴露将与海马[11C] UCB-J结合相关。 方法：我们将在禁欲前后比较cud的突触囊泡密度 [11C] UCB-J PET和高分辨率研究断层扫描。年龄，性别匹配健康对照（HCS） 还将在基线和4周进行扫描，以验证长期的测试重测稳定性。关系 海马[11C] UCB-J结合，口头记忆和大麻暴露的度量（启动年龄 使用和寿命暴露）将在CUD中探索。 试点数据：CUDS（n = 12）显示较低的海马SV2A和言语记忆，这是相关的。 cuds（n = 2） 显示出[11C] UCB-J结合的增加，并确认大麻的戒酒约4周。