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 青少年使用大麻比任何其他娱乐性药物都多。他们正在发育的大脑也可能 特别容易受到其影响，因为流行病学和实验证据表明 青春期频繁吸食大麻可能与认知和情感障碍有关 并在成年生活中持续发挥作用。过度刺激内源性大麻素（ECB） 系统 – 大麻主要精神活性成分 Δ9-四氢大麻酚 (THC) 的目标 – 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 NIDA 卓越中心，题为“大麻素的影响” 寿命（ICAL），检验 ECB 系统非生理激活的假设 青春期——由接触 THC 引起——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 这个系统，最终导致认知和动机行为的持续异常。测试 根据这一假设，ICAL 将部署一种垂直整合的战略，结合分子、 神经解剖学、电生理学和行为学方法。具体的机械问题将 根据需要解决现有技术，例如化学遗传学（DREADD） 控制神经回路的活动。 ICAL 内部的协同整合将通过 (a) 共享 行政核心将确保中心的无缝运作； (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对象来源 项目； (c) 一个试点核心，它将允许探索内部产生的重要新想法 或中心之外。一套结构化的措施（严格遵守治疗方案、动物 受试者随机化、盲测）将确保我们研究的严谨性和可重复性。广泛的 外展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、双月研讨会系列和国际“领域现状” 研讨会，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（通过一年一度的大麻意识日和网站 致力于该领域新科学发现的外行传播）。在这样的背景下 快速变化的法律、社会态度和经济利益，其持久的后果 青少年吸食大麻对大脑发育和心理功能的影响仍然很大程度上未知。 ICAL 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，以及 传播有关大麻及其功效的科学发现。