Synaptic Vesicle Density in Cannabis Dependence

大麻依赖性中的突触小泡密度

• 批准号: 9387557
• 负责人: DEEPAK Cyril D'SOUZA
• 金额: $ 25.13万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9387557
• 关键词: Abstinence; Acute; Adolescence; Adolescent; Adult; Affect; Age; Age-Years; Alzheimer' s Disease; Animals; Anterior; Anticonvulsants; Applications Grants; Auditory; Binding; Brain; Brain imaging; Brain region; CNR1 gene; Cannabinoids; Cannabis; Chronic; Cognition; Cognitive deficits; Data; Development; Distal; Electroencephalography; Electrophysiology (science); Event; Exposure to; Funding; Globus Pallidus; Glycoproteins; Hippocampus (Brain); Histologic; Human; Image; In Vitro; Individual; Insula of Reil; Keppra; Kinetics; Legal; Levetiracetam; Ligand Binding; Link; Magnetic Resonance Imaging; Marijuana Dependence; Measures; Medial; Medical; Membrane Proteins; Memory; Memory impairment; Metabolism; Methods; Modeling; Morphology; Outcome; Parahippocampal Gyrus; Penetration; Perception; Peripheral; Pharmaceutical Preparations; Phase; Population; Positron-Emission Tomography; Protein Isoforms; Proteins; Proxy; Research; Resolution; Risk; Rodent; Safety; Scalp structure; Schizophrenia; Signal Transduction; Specificity; Spices; Structure; Surface; Synapses; Synaptic Vesicles; Synaptophysin; Teenagers; Temporal Lobe; Testing; Tracer; Verbal Learning; Vertebral column; analog; cingulate cortex; cognitive function; density; early adolescence; emerging adult; gray matter; illicit drug use; in vivo; marijuana legalization; marijuana use; neuropsychiatric disorder; novel; parametric imaging; postsynaptic; putamen; radioligand; relating to nervous system; response; risk perception; synthetic cannabinoid; virtual; young adult

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.

项目摘要和摘要 背景：大麻是年轻人最常用的非法药物。大麻的效力 增加了高度潜在的合成大麻素（“香料”）。此外，“医疗”和 在美国，大麻的娱乐使用越来越多地合法化 对风险的看法 青少年的大麻使用 在过去的十年中有所下降 。大麻使用的倡议通常 发生在青少年和成年期间，当时大脑仍在发育，最容易受到伤害 侮辱，尤其是药物。因此，重要的是要了解慢性大麻素的后果 大脑的结构和功能接触。对两种啮齿动物的大麻素重复给药 已显示出降低突触密度，但这尚未在人类中进行研究。我们最近开发了 [11C] -UCB-J，用于体内突触囊泡蛋白SV2A成像的示踪剂。这个探索的目的 研究是为了比较大麻依赖受试者（CD）和健康对照（HCS）的突触密度和 将突触密度的变化与大脑活动的近端和不同度量相关，即诱发ɣ 脑电图和言语记忆中的振荡。此外，[11C] -UCB-J结合之间的关系， 引起的ɣ振荡，口头记忆和大麻暴露的度量（首次使用和生命时代的年龄 将探索曝光）。 假设：与HCS相比，CD将显示1）↓[11C] -UCB-J结合，2）↑在诱发的测量中定义 振荡和3）↑在口头记忆中定义。在CD受试者中，较低的[11C] UCB-J结合将是积极的 与早期使用大麻使用，终生大麻暴露，言语记忆和较差的年龄相关 更大的振荡定义了。 方法：我们将比较使用CDS（n = 12）与HCS（n = 12）中的突触密度进行比较 [11C] - UCB-J和高 分辨率研究断层扫描。 CD和HCS还将在诱发的e振荡的措施上进行比较 （听觉稳态响应：ASSR）和言语记忆（Rey听觉口头学习任务：RAVLT）。这 之间的关系 [11C] - UCB-J结合，诱发的ɣ振荡，言语记忆和大麻的度量 将探索暴露（使用和终生暴露年龄）。 试点数据：为了证明可行性，已经研究了CD（n = 2）和HC（n = 6）；显示的CD降低 在几个大脑区域中，SV2A的结合10％或更高（即大于测试 - 重度变异的边缘）。