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

6.项目摘要 大麻是美国最常滥用的非法药物，但目前还没有治疗方法。 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 根据药物滥用的网关理论，NIDA在过去几年的使命一直旨在确定安全和 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。这项建议的总体目标是测试一种天然的营养补充剂， 脑化学物质胞苷-5'-二磷酸胆碱（胞磷胆碱）对大麻诱导的中毒的影响， 虐待模式这种补充剂最近在一项赠款的开放标签试验中显示可以减少大麻的使用 根据RFA-DA-04 - 014（大麻相关疾病的药物开发）授予。因为 胞磷胆碱是哺乳动物脑内的一种天然化学物质，它相对安全， 中风和其他神经系统疾病。目前还不清楚大麻是如何影响大脑功能的，无论是急性的， 因此，拟议的研究旨在收集数据，作为 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 成像技术，如脑电图，磁共振成像和研究将 进行鉴定的作用机制，胞磷胆碱的影响，大麻使用和其中毒 方面的影响.作为设计治疗大麻依赖的药物的第一步，我们建议进行一项 在自然环境中胞磷胆碱对大麻使用模式的双盲、安慰剂对照评估。我们 然后将使用BOLD记录急性施用大麻对局部脑血流量的影响 信号检测最后，我们将研究胞磷胆碱是否改变大麻诱导的线索诱导的渴望。 总的来说，这些研究应该产生关于如何补充天然大脑的重要信息。 一种化学物质改变了大麻的作用，从而减少了大麻的使用。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， 拟议的项目可以提供重要的见解的病理生理学和过程中的大麻 依赖（以及潜在的其他药物依赖性障碍）。最后，由于没有任何副作用， 这些结果也可能为扩大相对有限的治疗选择提供重要的线索 对孕妇、吸毒成瘾母亲所生子女以及 青少年。

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.