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: 7782800
• 负责人: SCOTT E LUKAS
• 金额: $ 57.68万
• 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/7782800
• 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; 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; public health relevance; research study; response; success; theories; treatment duration; treatment strategy

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Marihuana is the most commonly abused illegal drug in the United States, yet there are no treatments for its abuse or dependence. Citicoline, a naturally occurring chemical in the brain, has been shown to reduce marihuana use in a pilot clinical trial. Using magnetic resonance brain imaging and EEG techniques, this application will explore the mechanism of action and develop new treatment strategies for marihuana dependence.

描述（由申请人提供）：大麻是美国最普遍滥用的非法药物，但没有滥用或依赖的治疗方法。作为一个重大的公共卫生问题，NIDA在过去几年中的任务旨在确定滥用大麻和依赖的安全有效候选疗法，尤其是那些可以给予弱势群体的人。该提案的总体目标是测试天然脑化学，胞苷5'-二磷酸胆碱（citicoline）的营养补充，其对大麻诱导的中毒和滥用模式的影响。最近显示，该补充剂可以减少大麻使用的赠款，该赠款是根据RFA-DA-04-014授予的（与大麻相关疾病的药物开发）授予的。由于citicoline是哺乳动物大脑中一种天然化学物质，因此它相对安全，并且在治疗中风和其他神经系统疾病方面非常有用。目前尚不清楚大麻如何急性化或长期使用后如何影响大脑功能，因此拟议的研究旨在收集数据，该数据将成为探索治疗大麻滥用的新策略的基础。这些目标将通过使用脑成像技术（例如脑电图，磁共振成像和研究）来实现，以确定citicoline对大麻使用及其醉人作用的作用机理。作为设计一种治疗大麻依赖的药物的第一步，我们建议在自然环境中对大麻使用模式进行双盲，安慰剂对照的评估。然后，我们将使用粗体信号检测来记录急性施用大麻对区域脑血流的影响。最后，我们将研究citicoline是否改变了大麻引起的提示引起的渴望。总的来说，这些研究应产生有关补充天然脑化学的重要信息，以改变大麻的作用，从而减少其使用。本系列研究的结果可能对大麻依赖性的药物疗法以及对与慢性使用相关的神经生物学损害的一级和次要预防具有重要意义。此外，拟议项目的结果可以为大麻依赖的病理生理学和过程提供重要的见解（以及其他药物依赖性疾病）。最后，鉴于缺乏citicoline的任何副作用，这些结果也可能为扩大弱势群体的相对有限的治疗选择（例如孕妇，毒品依赖的母亲和青少年所生的孩子）提供重要的潜在客户。公共卫生相关性：大麻是美国最常见的非法药物，但没有治疗其滥用或依赖性的治疗方法。辛蒂卡林（Citicoline）是大脑中天然存在的化学物质，已被证明可在试验临床试验中降低大麻的使用。使用磁共振脑成像和脑电图技术，该应用将探索作用机理，并为大麻依赖制定新的治疗策略。