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.

项目总结和摘要 背景：大麻是青年人最常使用的非法药物。大麻的功效 使用强效合成大麻素（“香料”）的情况也有所增加。此外，“医疗”和 大麻的娱乐性使用在美国越来越合法化。 对风险的看法 青少年吸食大麻 在过去的十年里， .开始使用大麻通常 发生在青春期和成年早期，此时大脑仍在发育，最容易受到 侮辱，尤其是毒品。因此，重要的是要了解慢性大麻素的后果 对大脑结构和功能的影响。对两种啮齿动物重复给予大麻素 已经被证明可以降低突触密度，但这还没有在人类身上进行研究。我们最近开发 [11 C]-UCB-J，一种用于体内突触囊泡蛋白SV 2A成像的示踪剂。这次探索的目的 研究是比较大麻依赖受试者（CD）和健康对照者（HC）的突触密度， 将突触密度的变化与大脑活动的近端和远端测量相关联，即诱发的突触密度 脑电波振荡和文字记忆此外，[11 C]-UCB-J结合， 诱发的脑电振荡、文字记忆和大麻暴露措施（首次使用年龄和寿命 将进行探索。 假设：与HC相比，CD将显示1）↓ [11 C]-UCB-J结合，2）↑诱发性β的测量缺陷 振荡，和3）↑缺陷的文字记忆。在CD受试者中，较低的[11 C]UCB-J结合将是积极的。 与开始使用大麻的年龄较早、终生接触大麻、文字记忆力较差以及 更大的赤字在振荡。 方法：我们将比较CD（n=12）与HC（n=12）中的突触密度， [11 C] ─ UCB-J和高 分辨率研究断层扫描仪。CD和HC也将在诱发的脑电振荡的测量上进行比较 （听觉稳态反应：ASSR）和言语记忆（雷伊听觉言语学习任务：RAVLT）。的 关系 [11 C] ─ UCB-J结合、诱发的脑电振荡、非文字记忆和大麻的测量 将探索暴露（开始使用的年龄和终生暴露）。 初步数据：为了证明可行性，研究了CD（n=2）和HC（n=6）; CD显示降低 SV 2A结合率为10%或更高（即，大于重测变异性的界限）。