Citicoline-Induced Modulation of Cannabis Effects: Imaging & Mechanism of Action

胞二磷胆碱诱导的大麻效应调节：成像

• 批准号: 8247729
• 负责人: SCOTT E LUKAS
• 金额: $ 57.35万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2013-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8247729
• 关键词: Acute; Address; Adolescent; Adverse effects; Affect; Area; Asia; Attenuated; Award; Behavior Therapy; Brain; Brain imaging; Cannabis; Cannabis Abuse; Cannabis-Related Disorder; Cerebrovascular Circulation; Chemicals; Child; Choline; Chronic; Clinical Trials; Cocaine; Controlled Clinical Trials; Country; Craniocerebral Trauma; Cues; Cytidine; Cytidine Diphosphate Choline; Data; Dependence; Detection; Development; Diphosphates; Disease; Dopamine; Double-Blind Method; Drug Addiction; Drug Kinetics; Drug abuse; Drug usage; Electroencephalography; Environment; European; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Goals; Grant; Image; Imaging Techniques; Individual; Intake; Intoxication; Knowledge; Laboratories; Magnetic Resonance; Magnetic Resonance Imaging; Marijuana; Marijuana Dependence; Measures; Mission; Mothers; Neurobiology; Neurodegenerative Disorders; Outcome; Participant; Pathway interactions; Pattern; Persons; Pharmaceutical Preparations; Pharmacotherapy; Phospholipid Metabolism; Physiological; Placebo Control; Placebos; Population; Pregnant Women; Primary Prevention; Public Health; Reporting; Research Design; Rewards; Secondary Prevention; Series; Signal Transduction; Smoking; Stroke; Supplementation; Techniques; Testing; United States; Vulnerable Populations; base; brain electrical activity; cocaine use; craving; cue reactivity; dietary supplements; experience; improved; insight; nervous system disorder; open label; research study; response; success; theories; treatment duration; treatment strategy

6. Project Summary Marihuana is the most commonly abused illegal drug in the United States, yet there are no treatments for its abuse or dependence. As a significant public health problem because of its known association with the Gateway theory of drug abuse, NIDA's mission over the past few years has been aimed at identifying safe and effective candidate therapies for marihuana abuse and dependence, particularly those that can be given to vulnerable populations. The overall objectives of this proposal are to test a nutritional supplement of the natural brain chemical, cytidine-5'-diphosphate choline (citicoline) for its effects on marihuana-induced intoxication and abuse patterns. This supplement was recently shown to reduce marihuana use in an open label trial of a grant that was awarded under RFA-DA-04-014 (Medication Development for Cannabis-Related Disorders). Because citicoline is a natural chemical in mammalian brain, it is relatively safe and has been very useful in treating stroke and other neurological disorders. It is still unclear how marihuana affects brain function, either acutely or after chronic use, so the proposed studies are designed to collect data that will serve as a foundation for exploring new strategies for treating marihuana abuse. These goals will be accomplished by using brain imaging techniques such as electroencephalography, magnetic resonance imaging and studies will be conducted to identify the mechanism of action of citicoline's effects on marihuana use and its intoxicating effects. As a first step in devising a medication to treat marihuana dependence we propose to conduct a double-blind, placebo-controlled assessment of citicoline on marihuana use patterns in a natural setting. We will then document the effects of acutely administered marihuana on regional cerebral blood flow using BOLD signal detection. Finally, we will study whether citicoline alters marihuana-induced cue-induced craving. Collectively, these studies should yield important information on how supplementation with a natural brain chemical alters marihuana's effects such that its use is decreased. The results of the present series of studies could have important implications for the pharmacotherapy of marihuana dependence as well as primary and secondary prevention of the neurobiological damage associated with chronic use. Furthermore, the outcome of the proposed project could offer important insights into the pathophysiology and course of marihuana dependence (and potentially on other drug dependence disorders). Lastly, given the lack of any side effects of citicoline, these results also may provide important leads for expanding the relatively limited treatment options for vulnerable populations such as pregnant women, children born to drug-dependent mothers and adolescents.

六、项目概要 大麻是美国最常滥用的非法药物，但目前尚无治疗方法 滥用或依赖。作为一个重大的公共卫生问题，因为它与已知的关联 药物滥用的门户理论，NIDA 在过去几年的使命一直是旨在识别安全和 治疗大麻滥用和依赖的有效候选疗法，特别是那些可以给予 弱势群体。该提案的总体目标是测试天然的营养补充剂 脑化学物质，胞苷-5'-二磷酸胆碱（胞二磷胆碱）对大麻引起的中毒有影响 滥用模式。最近，在一项拨款的开放标签试验中，该补充剂被证明可以减少大麻的使用 该奖项是根据 RFA-DA-04-014（大麻相关疾病的药物开发）授予的。因为 胞磷胆碱是哺乳动物大脑中的天然化学物质，相对安全，在治疗方面非常有用 中风和其他神经系统疾病。目前尚不清楚大麻如何影响大脑功能，无论是急性还是 长期使用后，因此拟议的研究旨在收集数据，作为基础 探索治疗大麻滥用的新策略。这些目标将通过使用大脑来实现 脑电图、磁共振成像等成像技术和研究将 旨在确定胞磷胆碱对大麻使用及其致醉作用的作用机制 影响。作为设计治疗大麻依赖药物的第一步，我们建议进行一项 双盲、安慰剂对照评估胞磷胆碱对自然环境中大麻使用模式的影响。我们 然后将使用 BOLD 记录急性施用大麻对局部脑血流的影响 信号检测。最后，我们将研究胞二磷胆碱是否会改变大麻引起的提示引起的渴望。 总的来说，这些研究应该提供关于如何补充天然大脑的重要信息 化学物质会改变大麻的作用，从而减少其使用。本系列研究的结果 可能对大麻依赖的药物治疗以及原发性和 与长期使用相关的神经生物学损伤的二级预防。此外，结果 拟议的项目可以为大麻的病理生理学和病程提供重要的见解 依赖性（以及可能对其他药物依赖性疾病）。最后，考虑到没有任何副作用 胞磷胆碱，这些结果也可能为扩大相对有限的治疗选择提供重要线索 对于孕妇、吸毒母亲所生的孩子等弱势群体 青少年。