Nabilone for Cannabis Dependence: Imaging and Neuropsychological Performance

描述（由申请人提供）：大麻使用障碍是美国的一个重要公共卫生问题，但没有有效的药物治疗可用于治疗这些障碍。我们打算测试一种新的激动剂药物治疗，大麻依赖，并研究这种治疗与大脑使用BOLD功能磁共振成像措施的关系。nabilone和9-THC的行为和生理作用重叠，表明nabilone可以改善大麻戒断症状，同时允许寻求治疗的门诊患者在试图停止使用大麻时从医疗管理（MM）中受益。我们建议评估nabilone添加到MM中时与大麻依赖患者大麻使用模式的关系。我们还旨在确定nabilone对神经心理学测试性能的影响，并使用BOLD功能磁共振成像测量评估神经心理学性能与大脑变化的相关性。 对于本申请的K99部分，我们将进行研究1，Nabilone治疗大麻依赖的初步研究：成像和神经心理学表现，其中受试者将在10周的治疗期内接受Nabilone或安慰剂以及药物管理（MM）。受试者对神经心理学测试的反应，同时受试者在3个时间点接受fMRI扫描：基线、4周和10周。治疗完成后，受试者将在第14周接受随访访视。这项试点研究将评估大麻依赖的纳必隆治疗的可行性，并将建立本申请R 00部分的效应量，研究2，大麻依赖的纳必隆：成像和神经心理学表现，一项更大的试验，其中受试者除了MM外还将接受高剂量的nabilone、低剂量的nabilone或安慰剂。受试者对神经心理学测试的反应将通过3次fMRI扫描来测量：在基线、4周和10周。在研究2中，受试者将在功能磁共振成像扫描仪内外接受神经心理学测试，这些技术是在K99阶段的研究1中学习的。 大麻使用障碍在美国非常普遍，并且在高中高年级学生中不断上升，因此确定大麻依赖的有效治疗方法具有重要的临床和公共卫生意义。在完成这些研究时，我们希望能够提高我们对大麻使用的nabilone关系的理解，并更好地了解药物，安慰剂和医疗管理对神经心理学测试和fMRI BOLD信号响应认知挑战范例的表现的关系，而在fMRI扫描仪中。 公共卫生相关性：我们打算测试一种新的激动剂药物治疗，大麻依赖，并研究这种治疗与大脑使用BOLD功能磁共振成像措施的关系。我们希望采取措施开发一种治疗大麻依赖的药物，这是一个重要的公共卫生问题。

DESCRIPTION (provided by applicant): Cannabis use disorders are an important public health problem in the United States, but no effective pharmacotherapies are available to treat these disorders. We intend to test a novel agonist pharmacotherapy, nabilone, for cannabis dependence and to study the relationship of this treatment with the brain using BOLD fMRI measures. The behavioral and physiological effects of nabilone and 9-THC overlap, suggesting that nabilone may ameliorate cannabis withdrawal symptoms while allowing treatment-seeking outpatients to benefit from medical management (MM) sessions when they are trying to stop using cannabis. We propose to assess the relationship of nabilone, when added to MM, on cannabis use patterns in cannabis-dependent patients. We also aim to determine the effects of nabilone on performance on neuropsychological tests and to assess the correlation of neuropsychological performance to brain changes using BOLD fMRI measures. For the K99 portion of this application, we will conduct Study 1, Pilot Study of Nabilone for Cannabis Dependence: Imaging and Neuropsychological Performance, in which subjects will receive either nabilone or placebo in addition to medical management (MM) over a 10-week treatment period. Subjects' responses to neuropsychological testing carried out while the subject is receiving fMRI scans at 3 time points: at baseline, 4 weeks, and 10 weeks. Following treatment completion, subjects will have a follow-up visit at 14 weeks. This pilot study will evaluate the feasibility of nabilone treatment for cannabis dependence and will establish effect sizes for the R00 portion of this application, Study 2, Nabilone for Cannabis Dependence: Imaging and Neuropsychological Performance, a larger trial in which subjects will receive high-dose nabilone, low-dose nabilone, or placebo in addition to MM. As in Study 1, subjects' responses to neuropsychological testing will be measured by 3 fMRI scans: at baseline, 4 weeks, and 10 weeks. In Study 2, subjects will undergo neuropsychological testing both inside and outside of the fMRI scanner, the techniques having been learned during Study 1 of the K99 phase. Cannabis use disorders are highly prevalent in the United States and rising among high school seniors, making the identification of efficacious treatments for cannabis dependence of critical clinical and public health significance. At the completion of these studies, we hope to have improved our understanding of the relationship of nabilone on cannabis use as well as have gained a better understanding of the relationship of medication, placebo, and medical management upon performance on neuropsychological testing and fMRI BOLD signaling in response to cognitive challenge paradigms administered while in the fMRI scanner. PUBLIC HEALTH RELEVANCE: We intend to test a novel agonist pharmacotherapy, nabilone, for cannabis dependence and to study the relationship of this treatment with the brain using BOLD fMRI measures. We hope to take steps toward developing a medication for cannabis dependence, an important public health problem.