ICAL: Impact of Cannabinoids Across Lifespan

项目摘要：概述 青少年使用大麻的次数比其他任何娱乐用药都多。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 青春期频繁使用大麻可能与认知和情感障碍有关 在成人生活中继续发挥作用。过度刺激内源性大麻素(ECB) 系统-大麻的主要精神活性成分Δ9-四氢大麻酚(THC)的目标-是 关于大麻使用的长期后果，一种看似合理但仍鲜为人知的机制。 我们提议建立一个NIDA英才中心，题为《大麻在全球的影响 寿命(Ical)，以检验欧洲央行系统的非生理性激活在 青春期--由接触THC引起--启动表观遗传驱动的 支配分子结构、神经解剖结构和突触功能的过程 这一系统最终会在认知和动机行为方面产生持续性的异常。为了测试 这一假设将部署一种垂直整合的策略，将分子、 神经解剖学、电生理学和行为学方法。具体的机械性问题将 应根据需要利用当前的技术，如化学遗传学(DREADD) 神经回路活动的控制。将通过(A)共享的 确保中心无缝运作的行政核心；(B)动物和分析 核心，这将为所有人提供一致的和特征明确的实验对象来源 项目；和(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。一套有组织的措施(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重复性。一个大女人 外联活动方案将针对科学界(通过本科生/研究生 学生和教师指导，双月系列研讨会和国际“最新情况” 讲习班，由同行评议杂志《大麻和大麻素研究》主办)，保健 专业人员和公众(通过一年一度的大麻宣传日和一个网站 致力于该领域新科学发现的长期传播)。在...的背景下 快速变化的法律、社会态度和经济利益，其持久后果 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不清楚。Ical‘s 使命是填补这一知识空白，同时增强我们对功能的机械性理解 由欧洲央行系统在大脑中提供服务，教育新一代大麻研究人员，以及 传播有关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.