The Effects of the Cannabinoid-1 Receptor Antagonist Rimonabant on Weight...

描述（由申请人提供）：本项目将研究一种新药利莫那班（一种大麻素CB1受体拮抗剂）在接受第二代抗精神病药物治疗的精神分裂症患者中减轻体重、改善代谢参数和心血管疾病风险的有效性和安全性。此外，本研究旨在测试辅助利莫那班对患者感知健康结果、生活质量、吸烟频率和神经认知功能的影响。这项为期16周的随机双盲安慰剂对照试验将招募60名BMI为bbbb30或bbbb27的受试者，这些受试者具有明确的心血管疾病危险因素。受试者注册必须在本奖项颁发后的24个月内完成。这项研究的结果将用于设计这种药物的进一步工作，以及其他可能可用的类似药物。精神分裂症患者患代谢综合征的风险是一般人群的四倍，精神分裂症中与体重相关的发病率和死亡率被认为是全球重大的健康负担。精神分裂症患者的死亡率也较高，患心血管疾病的相对风险几乎是一般人群的5倍。据信，由于新型抗精神病药物的使用，这一比例还在上升。这些新药物有显著的好处，但会引起体重增加和代谢异常的副作用，包括2型糖尿病和高脂血症。利莫那班是一种新药，已被证明可以显著降低体重和代谢参数，如超重人群的甘油三酯、空腹血糖、胰岛素敏感性和胆固醇。如果在精神分裂症人群（一群不太可能坚持或受益于运动和饮食调整的人）中发现安全有效，一种新的治疗方法将被证明可以显着改善这一群体的整体健康状况，并允许更有效地使用抗精神病药物。这项研究的结果将影响这一领域的其他工作。随着与利莫那班类似的抗肥胖药物的发展，利莫那班和其他大麻素受体拮抗剂是否会用于严重精神疾病是毫无疑问的。为了提供真正有效的治疗和进一步了解这些疾病，这些患者应该有疗效和安全性的直接证据。

DESCRIPTION (provided by applicant): This project will examine the efficacy and safety of a new medication, rimonabant, a cannabinoid CB1 receptor antagonist, in decreasing weight and improving metabolic parameters and cardiovascular disease risk in people with schizophrenia receiving second-generation antipsychotics. Additionally, the study aims to test the effects on adjunct rimonabant on patient perceived health outcomes, quality of life, smoking frequency and neurocognitive functioning. This 16 week randomized double-blind placebo controlled pilot study will enroll 60 subjects who have a BMI >30 or a BMI>27 with defined risk factors for cardiovascular disease. Subject enrollment should be completed within 24 months of this award. Results from this study will then be used to design further work with this drug, and other similar agents that may become available. There is a fourfold greater risk for metabolic syndrome in people with schizophrenia than in the general population and weight related morbidity and mortality in schizophrenia is considered a significant worldwide health burden. People with schizophrenia are also known to have increased mortality rates and the relative risk of having cardiovascular disease is almost 5 times higher than the general population. This rate is believed to be rising due to the use of new antipsychotic medications. These new medications have significant benefits, but cause the side effects of weight gain and metabolic abnormalities, including type II diabetes mellitus and hyperlipidemias. Rimonabant is a new medication that has been shown to significantly decrease weight and metabolic parameters, such as triglycerides, fasting glucose, insulin sensitivity and cholesterol in people who are overweight. If found safe and effective in the schizophrenia population, a group of people who are unlikely to adhere or benefit from exercise and dietary modifications, a new treatment method would be demonstrated that could markedly improve the overall health in this group and allow more effective use of antipsychotic medications. The results of this study will influence additional work in this area. With a strong development pipeline of antiobesity medications similar to rimonabant, there is no question whether rimonabant and other cannabinoid receptor antagonizing agents will be used in the seriously mentally ill. There should be direct evidence of efficacy and safety in these patients in order to provide truly effective treatments and further understanding of these disorders.