Nabilone for Cannabis Dependence: Imaging and Neuropsychological Performance

描述(申请人提供)：大麻使用障碍在美国是一个重要的公共卫生问题，但没有有效的药物疗法来治疗这些障碍。我们打算测试一种新的激动剂药物疗法，纳比隆，用于治疗大麻依赖，并使用大胆的fMRI措施研究这种治疗与大脑的关系。纳比隆和9-THC的行为和生理作用是重叠的，这表明纳比隆可以缓解大麻戒断症状，同时允许寻求治疗的门诊患者在试图停止使用大麻时受益于医疗管理(MM)会议。我们建议评估纳比隆与大麻依赖患者的大麻使用模式之间的关系。我们还旨在确定纳比隆对神经心理测试中表现的影响，并使用BOLD功能磁共振测量来评估神经心理表现与脑变化的相关性。对于这项申请的K99部分，我们将进行研究1，纳比隆治疗大麻依赖的试点研究：成像和神经心理表现，受试者将在为期10周的治疗期内，在药物治疗(MM)的基础上接受纳比隆或安慰剂。受试者在3个时间点：基线、4周和10周接受fMRI扫描时，对神经心理测试的反应。治疗结束后，受试者将在14周内进行随访。这项试点研究将评估纳比隆治疗大麻依赖的可行性，并将确定这一应用的R00部分的效果大小，研究2，纳比隆治疗大麻依赖：成像和神经心理表现，这是一项更大的试验，受试者将在MM的基础上接受高剂量纳比隆、低剂量纳比隆或安慰剂。与研究1一样，受试者对神经心理测试的反应将通过3次fMRI扫描来衡量：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，这些技术是在K99阶段的研究1中学到的。大麻使用障碍在美国非常普遍，并在高中生中呈上升趋势，这使得确定有效的大麻依赖治疗方法具有重要的临床和公共卫生意义。随着这些研究的完成，我们希望提高我们对纳比隆与大麻使用的关系的理解，并更好地理解药物、安慰剂和医疗管理对神经心理测试和fMRI BOLD信号的表现的关系，以响应在fMRI扫描仪中实施的认知挑战范例。 公共卫生相关性：我们打算测试一种新的激动剂药物疗法，纳比隆，用于治疗大麻依赖，并使用大胆的功能磁共振测量方法研究这种治疗与大脑的关系。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.