Cannabis Dependence: Imaging and Medication Development

大麻依赖：影像学和药物开发

• 批准号: 7091628
• 负责人: SCOTT E LUKAS
• 金额: $ 18.74万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/7091628
• 关键词: brain circulation; brain metabolism; cannabinoids; choline; clinical research; clinical trials; cognitive behavior therapy; combination therapy; cytosine nucleotides; drug abuse chemotherapy; drug addiction; drug withdrawal; electroencephalography; evoked potentials; functional magnetic resonance imaging; group counseling; human subject; human therapy evaluation; marijuana abuse; neurochemistry; neuropharmacology; neurophysiology; neuropsychological tests; nuclear magnetic resonance spectroscopy; patient oriented research; phospholipids; smoking

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 These effects will be compared to the acutely withdrawn brain and thus will serve as baselines to assess the efficacy of a novel medication, cytidine-5'- diphosphate choline (CDP-choline, citicoline) in reducing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）：该申请响应RFA-DA-04-014与大麻相关疾病的药物开发，从两个角度来解决大麻依赖性：1）量化大脑使用脑部摄影（EEG/ERP，ERP，FMRI和MR的策略）的急性，慢性和戒断效应，并旨在探讨这些策略，并旨在使用这些策略，以促进这些策略，以促进数据的发展。目前尚不清楚大麻如何急性地影响大脑功能，或者在长期使用之后，因此在大麻依赖和戒断过程中了解大脑功能的变化将极大地有助于我们对滥用大麻的神经生物学基础，因此将是开发新药物治疗这种疾病的重要基础。诸如fMRI和MRS之类的新的和改进的大脑成像技术为我们提供了一个独特的机会，可以查看这些微妙而重要的大脑功能变化。作为设计治疗大麻依赖性药物的第一步，我们建议仔细记录大麻对区域脑血流和脑化学的影响。这些作用将与急性拔出的大脑进行比较，因此将作为基准，以评估一种新型药物的疗效，细胞丁基5'-二磷酸胆碱（CDP-胆碱，citicoline）在减少大麻使用方面的使用，并逆转心理运动的性能缺陷，记忆力损失和睡眠分散，并在撤回大麻级和撤回大麻级。我们根据偶然发现的结果选择了citicoline，即它不仅可以减少我们正在进行的临床试验中可卡因的使用，而且还可以减少大麻吸烟。我们的实验利用了我们正在进行的可卡因依赖受试者的临床研究以及Pilot MR数据中获得的结果。如果有积极的话，这些结果可能对大麻依赖性的药物疗法以及对与慢性大麻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（以及对其他药物依赖性疾病的可能性）。由于治疗药物滥用的多学科方法是最成功的，因此我们将使用2 x 2的设计来测试citicoline和认知行为疗法（CBT）对失眠的组合，作为大麻依赖性的有效治疗方法。最后，鉴于citicoline缺乏任何副作用，这些结果也可能为扩大弱势群体的相对有限的治疗选择提供重要潜在客户，例如孕妇，毒品依赖的母亲和青少年所生。