Cerebellar biobehavioral markers in cannabis users

大麻使用者的小脑生物行为标记

• 批准号: 10116984
• 负责人: WILLIAM P HETRICK
• 金额: $ 54.32万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10116984
• 关键词: Accidents; Addictive Behavior; Adolescence; Adolescent; Adult; Advocate; Affect; Age; Age of Onset; Agonist; Anatomy; Animal Model; Anterior; Behavior; Behavioral; Brain; Brain region; CNR1 gene; Cannabis; Cerebellum; Cerebrum; Chronic; Cognitive; Cognitive deficits; Data; Equipment and supply inventories; Exposure to; Failure; Functional Magnetic Resonance Imaging; Functional disorder; Future; Health; Human; Impairment; Intoxication; Knowledge; Legal; Life; Ligands; Link; Lobular; Lobule; Longitudinal Studies; Marijuana; Measures; Meta-Analysis; Methods; Michigan; Monitor; Motor; Nature; Neurobiology; Neurologic; Pattern; Performance; Peripheral; Pharmaceutical Preparations; Population; Posture; Process; Protocols documentation; Psychotic Mood Disorders; Public Health; Research; Research Project Grants; Rest; Risk; Risk Assessment; Risk Factors; Seeds; Sensory; Signal Transduction; Son; Spinal; Structure; System; Testing; Tetrahydrocannabinol; Twin Studies; United States; base; behavior measurement; biobehavior; emerging adult; experimental study; eyeblink conditioning; field study; high risk population; marijuana use; marijuana user; mental function; neural circuit; neurobehavioral; neuroimaging; receptor; receptor density; relating to nervous system; response; social; trend; university student; young adult

Cannabis use represents a significant and increasing public health concern as social acceptance accompanies legalization of this drug for medicinal and recreational purposes. These factors make understanding the health consequences of cannabis (CB) urgent and critical. For example, a recent study found university students age 19-22 had the highest rate of CB use in the last 30 years, with 39% having used in the last year. The prevailing view is that CB is a significant public health risk factor because (1) use is associated with increased risk for health and accidents, (2) adolescent use likely disturbs crucial brain maturation processes; (3) chronic use has been associated with cognitive deficits and (4) people who use CB are at increased risk for psychotic and mood disorders. However, the assessment of risks associated with cannabis is currently incomplete and equivocal. The proposed research strongly advocates that understanding the risks (or lack thereof) depends critically on a neural circuit-informed approach to testing the integrity of brain systems known to be richly endowed with CB-relevant receptors that are altered in response to CB exposure. The principal psychoactive ingredient of CB is delta-9-tetrahydrocannabinol (THC), which acts as a ligand for widely distributed CB1 receptors in the human brain. CB1R density in cerebellum is one of the highest in the brain. Although measures of cerebellar function could provide sensitive probes for the neurobehavioral effects of CB use, they have rarely been tested in CB users, nor have they been explicitly linked to behavioral deficits. Specific Aim 1 will measure resting state functional connectivity (rsFC) between cerebellum sub-regions and established cortical resting state brain networks (RSNs). Specific Aim 2 will test: a) whether cerebellar fMRI activation during cerebellar-dependent delay eyeblink conditioning (dEBC) is reduced in CB users; and b) whether task-based cerebellar activations produce different patterns of RSN connectivity (using the 10 RSNs from Aim 1) that are differentially sensitive to CB use. Specific Aim 3 will test the sensitivity of a set of cerebellar-dependent behavioral tasks to CB use. Findings from the proposed research will likely identify the cerebellar paradigms and measures which are most affected in current CB users. If the strongly founded predictions are borne out, this set of measures could then be utilized in a wide range of studies, including 1) longitudinal studies of high risk groups and CB users which would be critical for future research projects, 2) direct administration of cannabis compounds in humans, 3) studies of comparable measures in animal models of cannabis use and consequences, 4) genetically informed familial and twin studies and 5) field studies of cannabis intoxication. Additionally, these protocols could be highly informative in parsing cerebellar circuits which have been implicated in a broad range of addictive behaviors.

大麻使用代表着社会接受的重大且日益严重的公共卫生关注 伴随该药物的合法化是出于药用和娱乐目的。这些因素构成了 了解大麻（CB）的健康后果紧急和关键。例如，最近的研究 发现19-22岁的大学生在过去30年中使用最高的CB使用率，其中39％用于 去年。主要观点是CB是重要的公共卫生风险因素，因为（1）使用与 随着健康和事故的风险增加，（2）青少年使用可能会扰乱至关重要的大脑成熟 过程； （3）长期使用与认知缺陷有关，（4）使用CB的人在 增加了精神病和情绪障碍的风险。但是，评估与大麻相关的风险是 目前不完整和模棱两可。拟议的研究强烈主张了解风险 （或缺乏）严格取决于神经电路的方法来测试大脑的完整性 已知的系统富含CB相关的受体，这些受体会因CB暴露而改变。 CB的主要精神活性成分是Delta-9-四氢大麻酚（THC），可作为配体的配体 在人脑中广泛分布的CB1受体。小脑中的CB1R密度是该小脑的最高之一 脑。尽管小脑功能的测量可以为神经行为效应提供敏感的探针 在CB使用中，很少在CB用户中测试过它们，也没有明确与行为缺陷链接。 特定目标1将测量小脑子区域之间的静止状态功能连接（RSFC） 建立的皮质静息状态大脑网络（RSN）。特定目标2将测试：a）小脑fMRI是否 CB用户中降低了小脑依赖性延迟举动调节（DEBC）的激活；和b） 基于任务的小脑激活是否产生不同的RSN连接模式（使用10个RSN 来自AIM 1）对CB使用差异敏感的。特定目标3将测试一组的灵敏度 小脑依赖于CB使用的行为任务。拟议研究的发现可能会确定 在当前CB用户中受到影响最大的小脑范式和措施。如果坚强的建立 预测已经证实，可以在广泛的研究中使用这组措施，包括1） 对未来研究项目至关重要的高风险群体和CB使用者的纵向研究，2） 直接施用人类中的大麻化合物，3）动物模型中可比较测量的研究 大麻的使用和后果，4）遗传知情的家族和双胞胎研究以及5） 大麻中毒。此外，这些协议在解析小脑电路时可能具有很高的信息 这与广泛的成瘾行为有关。