ICAL: Impact of Cannabinoids Across Lifespan

ICAL：大麻素对整个生命周期的影响

• 批准号: 10188473
• 负责人: Daniele Piomelli
• 金额: $ 218.42万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10188473
• 关键词: Acute; Address; Adherence; Adolescence; Adolescent; Adult; Affective; Age; Animals; Architecture; Attitude; Awareness; Behavior; Behavior Therapy; Behavioral; Brain; Cannabinoids; Cannabis; Cognition; Cognitive; Communities; Comprehension; Data; Dependence; Development; Economics; Educational workshop; Electrophysiology (science); Emotional; Endocannabinoids; Ensure; Epidemiology; Epigenetic Process; Evaluation; Exposure to; Faculty; Fostering; General Population; Generations; Health Professional; Hippocampus (Brain); Impairment; Injections; Institution; International; Journals; Knowledge; Laws; Legal; Life; Literature; Longevity; Maintenance; Measures; Mediating; Medical; Methodology; Mission; Molecular; Molecular Structure; Molecular Target; Motivation; Mus; National Institute of Drug Abuse; Neurosciences; Nucleus Accumbens; Outcome; Peer Review; Physiological; Prefrontal Cortex; Process; Protocols documentation; Public Health; Public Policy; Randomized; Rattus; Receptor Activation; Recreational Drugs; Regimen; Reproducibility; Research; Research Personnel; Rewards; Series; Signal Transduction; Source; Stimulus; Structure; Synapses; System; Techniques; Teenagers; Testing; Tetrahydrocannabinol; Time; Training; Treatment Protocols; Ursidae Family; Ventral Striatum; addiction; adolescent health; behavioral outcome; blind; cannabinoid receptor; critical period; design; designer receptors exclusively activated by designer drugs; endogenous cannabinoid system; faculty mentor; gain of function; graduate student; high standard; interest; loss of function; marijuana use; mature animal; mental function; middle age; motivated behavior; neural circuit; neurobehavioral; neuroregulation; next generation; operation; outreach program; postnatal; programs; relating to nervous system; sex; social; student mentoring; synaptic function; synergism; undergraduate student; web site

PROJECT SUMMARY: OVERVIEW Teenagers use cannabis more than any other recreational drug. Their developing brains may also be especially vulnerable to its effects, as epidemiological and experimental evidence suggests that frequent cannabis use in adolescence may be associated with impairments in cognitive and affective functioning that continue in adult life. Excessive stimulation of the endogenous cannabinoid (ECB) system – the target of cannabis’s main psychoactive component, Δ9-tetrahydrocannabinol (THC) – is a plausible but still poorly understood mechanism for the long-lasting consequences of cannabis use. We propose the creation of a NIDA Center of Excellence, entitled Impact of Cannabinoids Across Lifespan (ICAL), to test the hypothesis that non-physiological activation of the ECB system in adolescence – caused by exposure to THC – initiates an epigenetically driven reprogramming of the processes that govern the molecular structure, neuroanatomical architecture and synaptic functions of this system, ultimately producing persistent abnormalities in cognition and motivated behavior. To test this hypothesis, ICAL will deploy a vertically integrated strategy combining molecular, neuroanatomical, electrophysiological and behavioral approaches. Specific mechanistic questions will be addressed bringing to bear, as needed, current techniques such as chemogenetic (DREADD) control of neural circuit activity. Synergistic integration within ICAL will be fostered by (a) a shared Administrative Core that will ensure the seamless operation of the center; (b) Animal and Analytical Cores, which will provide a consistent and well-characterized source of experimental subjects for all projects; and (c) a Pilot Core, which will allow for the exploration of important new ideas arising inside or outside the center. A structured set of measures (strict adherence to treatment protocols, animal subject randomization, blind-testing) will ensure the rigor and reproducibility of our studies. A broad program of outreach activities will target the scientific community (through undergraduate/graduate student and faculty mentoring, a bimonthly seminar series and an international “state-of-the-field” workshop, sponsored by the peer-reviewed journal Cannabis and Cannabinoid Research), health care professionals and general public (through an annual Cannabis Awareness Day and a website dedicated to the lay-term dissemination of new scientific discoveries in the field). In a context of rapidly changing laws, social attitudes and economic interests, the enduring consequences of adolescent cannabis use on brain development and mental function remain largely unknown. ICAL’s mission is to fill this knowledge gap while enhancing our mechanistic understanding of the functions serves by the ECB system in the brain, educating a new generation of cannabinoid researchers, and disseminating scientific discoveries about cannabis and its effects.

项目摘要：概述 青少年比其他任何休闲药物都多使用大麻。他们发育中的大脑也可能是 特别容易受到其影响，因为流行病学和实验证据表明 在青春期中，大麻通常与认知和情感的损害有关 在成人生活中持续的运作。过度刺激内源性大麻素（ECB） 系统 - 大麻主要的精神活性成分Δ9-四氢大麻醇（THC）的目标 - 对于大麻使用的长期后果，一种合理但仍然不太了解的机制。 我们建议建立一个NIDA卓越中心，名为“大麻素的影响” 寿命（ICAL），以检验以下假设：欧洲央行系统非生理激活 青少年 - 由暴露于THC引起的青少年 - 启动了表观遗传驱动的重编程 控制分子结构，神经解剖结构和突触功能的过程 该系统最终在认知和融合行为方面产生持续的异常。测试 这个假设，ICal将部署一种结合分子的垂直整合策略， 神经解剖学，电生理和行为方法。具体的机械问题将 可以根据需要解决熊，例如化学遗传（dreadd） 控制神经回路活动。 ICAL内的协同整合将由（a）共享 行政核心将确保中心的无缝操作； （b）动物和分析 核心将为所有人提供一致且特征良好的实验主题来源 项目； （c）飞行员核心，该核心将允许探索内部出现的重要新想法 或外面。一组结构化的措施（严格遵守治疗方案，动物 主体随机化，盲目测试）将确保我们的研究的严格性和可重复性。广泛 外展活动计划将针对科学界（通过本科/等级 学生和教师指导，每两个月开创性的系列和国际“最新场地” 讲习班，由同行评审期刊大麻和大麻素研究赞助），医疗保健 专业人士和公众（通过年度大麻意识日和网站 致力于对该领域的新科学发现的外行传播）。在 迅速变化的法律，社会吸引力和经济利益，持久的后果 青少年大麻在大脑发育和心理功能上的使用仍在很大程度上未知。 iCal 使命是填补这一知识差距，同时增强我们对功能的机械理解 由大脑中的欧洲央行系统服务，教育新一代的大麻素研究人员，并 传播有关大麻及其影响的科学发现。