ICAL: Impact of Cannabinoids Across Lifespan

项目概要：概述 青少年使用大麻比任何其他娱乐性药物都多。它们发育中的大脑也可能 流行病学和实验证据表明， 青少年频繁使用大麻可能与认知和情感障碍有关。 在成年生活中继续发挥作用。内源性大麻素（ECB）的过度刺激 系统-大麻的主要精神活性成分Δ9-四氢大麻酚（THC）的目标-是 这是大麻使用的长期后果的一个看似合理但仍知之甚少的机制。 我们建议建立一个NIDA卓越中心，名为大麻素对全球的影响。 寿命（ICAL），以检验ECB系统的非生理激活在 青春期-由暴露于THC引起-启动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 这个系统，最终产生持续的认知和动机行为异常。测试 根据这一假设，ICAL将部署一种垂直整合的策略， 神经解剖学、电生理学和行为学方法。具体的机械问题将 根据需要，利用目前的技术，如化学遗传学（DREADD） 控制神经回路活动将通过以下方式促进国际比较研究所内部的协同一体化：（a） 确保中心无缝运行的管理核心;（B）动物和分析 核心，这将提供一个一致的和良好的特点来源的实验对象，为所有 项目;以及（c）试点核心，这将允许探索内部产生的重要新想法 或者在中心之外。一套结构化的措施（严格遵守治疗方案，动物 受试者随机化、盲法测试）将确保我们研究的严谨性和可重复性。广泛 外联活动计划将针对科学界（通过本科生/研究生 学生和教师指导，双月研讨会系列和国际“国家的领域” 研讨会，由同行评审期刊《大麻和大麻素研究》主办），卫生保健 专业人员和公众（通过年度大麻宣传日和网站 致力于传播该领域的新科学发现）。背景下 迅速变化的法律、社会态度和经济利益， 青少年使用大麻对大脑发育和精神功能的影响在很大程度上仍然未知。ICAL的 我们的使命是填补这一知识空白，同时增强我们对功能的机械理解 由大脑中的ECB系统提供服务，教育新一代大麻素研究人员， 传播关于大麻及其影响的科学发现。

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.