Cannabis Dependence: Imaging and Medication Development

大麻依赖：影像学和药物开发

基本信息

批准号：
6879349
负责人：
SCOTT E LUKAS
金额：
$ 12.92万
依托单位：
MCLEAN HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-24 至 2006-08-31
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): This application, in response to RFA-DA-04-014 Medication Development for Cannabis-Related Disorders, addresses cannabis dependence from two perspectives: 1) quantifying the acute, chronic and withdrawal effects of cannabis using brain imaging (EEG/ERP, fMRI and MRS) and 2) using these data to serve as a foundation for exploring new strategies for cannabis medication development. It is unclear how cannabis affects brain function, either acutely or after chronic use so knowledge of the changes in brain function during cannabis dependence and withdrawal will aid greatly in our understanding of the neurobiological bases of cannabis abuse and will thus serve as an important foundation for developing new medications to treat this disorder. New and improved brain imaging techniques such as fMRI and MRS offer us a unique opportunity to view these subtle, yet important changes in brain function. As a first step in devising a medication to treat cannabis dependence we propose to carefully document the effects of acutely administered cannabis on regional cerebral blood flow and brain chemistry. These effects will be compared to the acutely withdrawn brain and thus will serve as baselines to assess the efficacy of a novel medication, cytidine-5'- diphosphate choline (CDP-choline, citicoline) in reducing cannabis use, and reversing the psychomotor performance deficits, memory loss and sleep disorders that occur during cannabis intoxication and withdrawal. We chose citicoline based on our serendipitous findings that it reduces not only cocaine use in our ongoing clinical trial, but appears to reduce marihuana smoking as well. Our experiments capitalize on the results obtained in our ongoing clinical studies of cocaine-dependent subjects along with pilot MR data. If positive, these results could have important implications for the pharmacotherapy of cannabis dependence as well as primary and secondary prevention of neurobiological damage associated with chronic cannabis use. Furthermore, the outcome of the proposed project could offer important insights into the pathophysiology and course of cannabis dependence (and potentially on other drug dependence disorders). As multidisciplinary approaches to treating drug abuse have been the most successful, we will use a 2 x 2 design to test the combination of citicoline and cognitive behavioral therapy (CBT) for insomnia as an effective treatment for cannabis dependence. 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.

描述（由申请人提供）：本申请响应 RFA-DA-04-014 大麻相关疾病药物开发，从两个角度解决大麻依赖问题：1) 使用脑成像量化大麻的急性、慢性和戒断效应（EEG/ERP、fMRI 和 MRS）和 2）使用这些数据作为探索大麻药物开发新策略的基础。目前还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，因此了解大麻依赖和戒断期间大脑功能的变化将极大地帮助我们了解大麻滥用的神经生物学基础，从而成为重要的基础。开发新药物来治疗这种疾病。新的和改进的大脑成像技术，如功能磁共振成像和磁共振成像技术，为我们提供了一个独特的机会来观察大脑功能中这些微妙但重要的变化。作为设计治疗大麻依赖的药物的第一步，我们建议仔细记录急性施用大麻对局部脑血流和脑化学的影响。这些效果将与急性退缩的大脑进行比较，从而作为评估新型药物胞苷-5'-二磷酸胆碱（CDP-胆碱，胞二磷胆碱）在减少大麻使用和扭转精神运动表现缺陷方面的功效的基线大麻中毒和戒断期间发生的记忆丧失和睡眠障碍。我们根据我们的偶然发现选择了胞磷胆碱，即它不仅减少了我们正在进行的临床试验中可卡因的使用，而且似乎也减少了吸食大麻。我们的实验利用了我们正在进行的可卡因依赖受试者临床研究中获得的结果以及试点 MR 数据。如果呈阳性，这些结果可能对大麻依赖的药物治疗以及与长期使用大麻相关的神经生物学损伤的一级和二级预防产生重要影响。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（以及可能的其他药物依赖障碍）提供重要的见解。由于治疗药物滥用的多学科方法是最成功的，我们将使用 2 x 2 设计来测试胞二磷胆碱和认知行为疗法 (CBT) 相结合治疗失眠症作为大麻依赖的有效治疗方法。最后，鉴于胞磷胆碱没有任何副作用，这些结果也可能为扩大弱势群体（例如孕妇、吸毒母亲所生的孩子和青少年）相对有限的治疗选择提供重要线索。