Cannabis & Schizophrenia: fMRI Reward Circuit Biomaker

大麻

• 批准号: 6952697
• 负责人: ALAN I GREEN
• 金额: $ 19.99万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6952697
• 关键词: Cannabis; behavioral /social science research tag; bioimaging /biomedical imaging; biomarker; brain electrical activity; brain metabolism; clinical research; clinical trials; clozapine; comorbidity; data collection; drug abuse chemotherapy; functional magnetic resonance imaging; health behavior; human subject; human therapy evaluation; neuroanatomy; neuropharmacology; neuropsychology; patient oriented research; pharmacokinetics; psychopharmacology; reinforcer; risperidone; schizophrenia

DESCRIPTION (provided by applicant): Cannabis use disorder (CUD), common in patients with schizophrenia (SCHIZ), contributes greatly to the morbidity of SCHIZ. Although typical antipsychotic medications do not control cannabis use in these patients, preliminary data from our group and others suggest that the atypical antipsychotic drug clozapine (CLOZ) may limit cannabis use in patients with SCHIZ much more effectively than do either typical antipsychotics or the "novel" (post-CLOZ) antipsychotics risperidone (RISP) or olanzapine (OLAN). We are conducting a NIDA funded (DA 13196) 12-week randomized clinical trial to further assess CLOZ effects on cannabis use, clinical symptoms/quality of life in patients with schizophrenia and comorbid CUD, as compared to patients treated with RISP or OLAN. This R21 application proposes an "add-on" functional MRI (fMRI) pilot study of brain reward circuitry to this "base" study. We have previously hypothesized that CLOZ (but not RISP, OLAN or typical antipsychotics) will help normalize dysfunctional brain reward circuits that may underlie comorbid cannabis use in SCHIZ. In this "add-on" study, a sub-sample of 24 RISP treated patients from the "base" study will undergo an fMRI monetary reward probe of brain reward circuit while being treated with RISP. In the "base" study, half of these patients will be randomized to CLOZ and half will remain on RISP for the 12- week clinical trial; in the "add-on" study, all patients will have repeat fMRI reward circuit testing at 12 weeks, and a matched group of normal controls will also be tested, twice (at recruitment and at 12 weeks). The proposed study will attempt to identify a potential imaging biomarker" of the action of CLOZ (as compared to RISP) on brain reward circuits. The overarching hypothesis for this research is that patients treated with RISP will demonstrate deficiencies in response to a brain reward circuit probe compared to normal controls and that these deficiencies will be normalized in patients treated with CLOZ. We also predict that there will be a relationship between the normalization of brain reward circuit response and decrease in cannabis use by patients. We expect this research to lead to an efficient method for testing medications that putatively may decrease cannabis use in SCHIZ. This is of great importance because, despite the benefits of CLOZ, its toxicity discourages many clinicians from using it. Finding new medications, safer than CLOZ, that may be able to limit cannabis use In patients with SCHIZ is thus of considerable public health relevance.

描述（由申请人提供）：大麻使用障碍（CUD）在精神分裂症（SCHIZ）患者中很常见，极大地增加了 SCHIZ 的发病率。尽管典型的抗精神病药物不能控制这些患者的大麻使用，但我们小组和其他人的初步数据表明，非典型抗精神病药物氯氮平 (CLOZ) 可能比典型的抗精神病药物或“新型抗精神病药物”更有效地限制 SCHIZ 患者的大麻使用。 “（CLOZ 后）抗精神病药利培酮 (RISP) 或奥氮平 (OLAN)。我们正在进行一项 NIDA 资助的 (DA 13196) 12 周随机临床试验，以进一步评估与接受 RISP 或 OLAN 治疗的患者相比，CLOZ 对精神分裂症和合并 CUD 患者的大麻使用、临床症状/生活质量的影响。该 R21 应用提出了一项针对“基础”研究的大脑奖励回路的“附加”功能 MRI (fMRI) 试点研究。我们之前假设 CLOZ（但不是 RISP、OLAN 或典型的抗精神病药物）将有助于使功能失调的大脑奖赏回路正常化，这可能是 SCHIZ 合并大麻使用的基础。在这项“附加”研究中，来自“基础”研究的 24 名 RISP 治疗患者的子样本将在接受 RISP 治疗的同时接受大脑奖励回路的功能磁共振成像金钱奖励探针。在“基础”研究中，一半患者将被随机分配至 CLOZ 组，一半患者将继续接受 RISP 组以进行为期 12 周的临床试验；在“附加”研究中，所有患者将在第 12 周时重复进行 fMRI 奖励回路测试，并且还将对一组匹配的正常对照进行两次测试（招募时和第 12 周时）。拟议的研究将尝试识别 CLOZ（与 RISP 相比）对大脑奖励回路作用的潜在成像生物标志物。这项研究的总体假设是，接受 RISP 治疗的患者将表现出对大脑奖励回路反应的缺陷我们还预测，大脑奖赏回路反应的正常化与患者大麻使用量的减少之间存在联系。一个测试可能减少 SCHIZ 大麻使用的药物的有效方法这一点非常重要，因为尽管 CLOZ 有好处，但它的毒性阻碍了许多临床医生寻找比 CLOZ 更安全的新药物，这可能能够限制 CLOZ 的使用。因此，SCHIZ 患者使用大麻具有相当大的公共卫生相关性。