Nabilone for Cannabis Dependence: Imaging and Neuropsychological Performance

Nabilone 治疗大麻依赖：影像学和神经心理学表现

• 批准号: 8656086
• 负责人: KEVIN P. HILL
• 金额: $ 24.89万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-05-01 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8656086
• 关键词: Agonist; Behavioral; Brain; Brain imaging; Cannabis; Chemotherapy-Oncologic Procedure; Clinical; Clinical Trials; Cognitive; Disease; Dose; FDA approved; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Image; Imaging Techniques; Individual; Learning; Marijuana Dependence; Measurement; Measures; Medical; Nabilone; Nausea and Vomiting; Neurobiology; Neuropsychological Tests; Outcome; Outpatients; Participant; Patient Self-Report; Patients; Pattern; Performance; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physiological; Pilot Projects; Placebos; Public Health; Scanning; Signal Transduction; Techniques; Testing; Time; United States; Visit; Withdrawal Symptom; base; cannabinoid receptor; experience; follow-up; imaging modality; improved; neuroimaging; neuropsychological; novel; response; treatment duration; twelfth grade

ABSTRACT 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.

摘要 大麻使用障碍是美国一个重要的公共卫生问题，但并不有效 治疗这些疾病有药物疗法可用。我们打算测试一种新的激动剂药物疗法， 纳比隆，用于大麻依赖，并使用BOLD研究这种治疗与大脑的关系 功能磁共振成像测量。纳贝酮和β9-THC的行为和生理作用是重叠的，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 当他们试图停止使用大麻时，从医疗管理(MM)会议中受益。我们建议 评估纳贝酮与大麻依赖患者的大麻使用模式的关系 病人。我们还旨在确定纳比隆对神经心理测试成绩的影响，并 使用BOLD功能磁共振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，大麻用纳比隆的试验研究 依赖：成像和神经心理表现，受试者将接受纳比隆或 在为期10周的治疗期间，在药物管理(MM)的基础上加用安慰剂。受试者对以下问题的反应 当受试者在3个时间点接受fMRI扫描时进行的神经心理测试：基线，4 几周，还有10周。治疗结束后，受试者将在14周内进行随访。这 初步研究将评估纳比隆治疗大麻依赖的可行性，并将确定效果 本申请的R00部分的大小，研究2，大麻依赖的纳比隆：成像和 神经心理表现，一项更大的试验，受试者将接受高剂量、低剂量的纳比隆 在研究1中，受试者对神经心理测试的反应将 通过3次fMRI扫描进行测量：基线、4周和10周。在研究2中，受试者将经历 FMRI扫描仪内外的神经心理测试，技术已被学习 在K99阶段的研究1期间。 大麻使用障碍在美国非常普遍，在高中生中呈上升趋势， 确定危重临床和公共卫生大麻依赖的有效治疗方法 意义。在这些研究完成后，我们希望能加深我们对 纳比隆与大麻使用的关系以及更好地了解 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表现的影响 在功能磁共振扫描仪中对认知挑战范例的反应进行大胆的信号传递。