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一个重要的公共卫生问题，但没有有效的药物疗法可用于治疗这些障碍。我们打算测试一种用于大麻依赖的新型激动剂药物治疗，纳比龙，并使用BOLD功能磁共振成像测量研究这种治疗与大脑的关系。纳比龙和9-四氢大麻酚的行为和生理效应重叠，表明纳比龙可以改善大麻戒断症状，同时使寻求治疗的门诊患者在试图停止使用大麻时受益于医疗管理（MM）。我们建议评估纳比龙的关系，当添加到MM时，大麻依赖患者的大麻使用模式。我们还旨在确定纳比龙对神经心理测试表现的影响，并使用BOLD功能磁共振成像测量评估神经心理表现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，纳比龙对大麻依赖的试点研究：成像和神经心理学表现，在10周的治疗期间，受试者将接受纳比龙或安慰剂，以及医疗管理（MM）。在基线、第4周和第10周三个时间点，受试者接受fMRI扫描时对神经心理测试的反应。治疗完成后，受试者将在14周进行随访。这项初步研究将评估纳比龙治疗大麻依赖的可行性，并将为该应用程序的R00部分建立效应大小，研究2，纳比龙治疗大麻依赖：成像和神经心理学表现，这是一项更大的试验，受试者将接受高剂量纳比龙、低剂量纳比龙或安慰剂，以及MM。与研究1一样，受试者对神经心理学测试的反应将通过3次功能磁共振成像扫描来测量：在基线，4周和10周。在研究2中，受试者将接受fMRI扫描仪内外的神经心理测试，这些技术已经在K99阶段的研究1中学习过。大麻使用障碍在美国非常普遍，而且在高中高年级学生中呈上升趋势，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。在完成这些研究后，我们希望能够提高我们对大麻使用与纳比龙之间关系的理解，并更好地了解药物、安慰剂和医疗管理对神经心理测试和功能磁共振成像BOLD信号响应认知挑战范式的影响，同时在功能磁共振成像扫描仪中进行。

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.