Understanding the Effects of Chronic Opioids Therapy in Humans

了解慢性阿片类药物治疗对人类的影响

基本信息

批准号：
8636421
负责人：
LAWRENCE F CHU
金额：
$ 12.67万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-01 至 2018-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8636421
关键词：
12 year old Acute Address Affect American Analgesics Anesthesia procedures Animal Model Award Brain Brain imaging Categories Chronic Clinical Clinical Research Collaborations Data Development Drug abuse Drug usage Environment Epidemiology Exposure to Fostering Functional Magnetic Resonance Imaging Funding Goals Haplotypes Health Home environment Human Human Volunteers Hydrocodone/Acetaminophen Image Immune system Immunologic Monitoring Independent Scientist Award Inflammation Inflammation Process Inflammatory Response Injury Institutional Review Boards K-Series Research Career Programs Knowledge Laboratories Lead Learning Link Maps Measures Mentorship Methods Modality Morphine Naloxone Ondansetron Opioid Pain Pain management Patient Care Patients Pattern Pharmaceutical Preparations Pharmacogenetics Physical Dependence Physicians Physiology Placebos Policy Research Prevention Public Health Publications Recording of previous events Reporting Research Research Personnel Research Proposals Scientist Senior Scientist Sensory Serotonin Antagonists Site Symptoms Testing Training Translating United States National Institutes of Health Universities Vicodin Withdrawal Symptom Work addiction base career career development cost cytokine immunoregulation improved interest male medical schools novel opioid withdrawal prescription opioid prescription opioid abuse prevent public health relevance receptor responsible research conduct skills symposium

项目摘要

DESCRIPTION (provided by applicant): The PI is a newly independent scientist (1R01DA029078-01A1) who is a physician and clinical researcher at Stanford University. This award will provide a period of intensive research focus that will allow the PI to enhance his research career (see RESEARCH). This award will also be used to foster the development of the candidate in order to expand his potential to make significant research contributions (see CANDIDATE). CANDIDATE: The PI is a newly independent scientist (1R01DA029078-01A1) with a history of previous NIH career development award funding (K23GM071400; NIH Clinical Research LRP), who will use the K02 award to pursue further career development activities in order to expand his potential to make significant research contributions. These activities include training in the responsible conduct of research, collaboration with senior researchers to develop new modes of inquiry, conference participation, further study proposals, research mentorship, and publication of quality research that translates directly to patient care. ENVIRONMENT: The PI's 400 sq. ft. human opioid physiology laboratory is situated in the Stanford School of Medicine, a hub of scientific activity and home to the 2008 and 2011 Center of Excellence-Winning Pain Management Center. The PI has active research collaborations with the Human Immune Monitoring Core and Lucas fMRI Imaging Center facilities at Stanford, in addition to ongoing relationships with senior scientists in the Epidemiology and Health Research Policy Departments. These facilities and collaborative relationships make Stanford an optimal environment to support the objectives of this award. RESEARCH: Currently, opioids are among the most common medications prescribed by physicians in the US and Vicodin (hydrocodone/acetaminophen) is the most prescribed medication of any category. However, physical dependence (PD), addiction, and opioid withdrawal (OW) complicate the use of prescription opioids. Among all Americans age 12 years and older in 2006, 13.6% (more than 33 million) reported having used prescription opioids for nonmedical purposes at least once, more than 12 million in the prior year, and 5.2 million in the prior month. Recent evidence from studies employing pharmacogenetic haplotype-based computational mapping have linked the 5HT3 receptor to PD and OW. Additional data from the PI's preliminary research show that 5HT3 receptor antagonists (RAs) can significantly decrease objective measures of opioid withdrawal in humans. The PI's current studies will evaluate the use of 5HT3-RAs for new indications in the treatment and prevention of prescription opioid drug abuse. Additional studies in the PI's lab aim to uncover the effects of chronic opioid therapy on human physiology through novel modalities, including fMRI and immunomodulation of opioid-induced changes. The implications of these research findings are substantial. By providing an effective, easily deliverable, low-cost method to mitigate the symptoms of OW and prevent the development or progression of PD, 5HT3-RA medications could drastically improve the treatment of pain.

描述（由申请人提供）：PI是一位新独立的科学家（1R01DA029078-01A1），是斯坦福大学的医师和临床研究员。该奖项将提供一个深入的研究重点，这将使PI能够增强他的研究生涯（请参阅研究）。该奖项还将用于促进候选人的发展，以扩大他做出重大研究贡献的潜力（请参阅候选人）。候选人：PI是一位新独立的科学家（1R01DA029078-01A1），具有先前NIH职业发展奖资金的历史（K23GM071400； NIH Clinical Research LRP），他们将利用K02奖，以寻求K02的职业发展活动，以扩大其潜在的潜力，以促进重大的研究贡献。这些活动包括在负责任进行研究的培训，与高级研究人员合作开发新的探究模式，会议参与，进一步的研究建议，研究指导以及直接转化为患者护理的质量研究。环境：PI的400平方英尺。人类阿片类生理实验室位于斯坦福医学院，这是科学活动的枢纽，是2008年和2011年卓越疼痛管理中心的所在地。 PI与斯坦福大学的人类免疫监测核心和卢卡斯fMRI成像中心设施进行了积极的研究合作，此外还有与流行病学和健康研究政策部门的高级科学家的持续关系。这些设施和协作关系使斯坦福大学成为支持该奖项目标的最佳环境。研究：目前，阿片类药物是美国医生规定的最常见的药物之一，vicodin（氢可酮/对乙酰氨基酚）是任何类别中规定的药物最常见的药物。但是，身体依赖（PD），成瘾和阿片类药物提取（OW）使处方阿片类药物的使用复杂。在2006年的所有12岁及以上的美国人中，有13.6％（超过3300万）报告说，在非医学目的中使用处方阿片类药物至少一次使用了一次，上一年超过1200万，在上个月使用了520万。采用药物遗传学单倍型的计算映射的研究的最新证据将5HT3受体与PD和OW联系起来。 PI初步研究的其他数据表明，5HT3受体拮抗剂（RAS）可以显着降低人类阿片类药物戒断的客观度量。 PI目前的研究将评估5HT3-RAS在治疗和预防处方阿片类药物滥用方面的新适应症。 PI实验室中的其他研究旨在通过新型的方式揭示慢性阿片类药物治疗对人类生理的影响，包括fMRI和阿片类药物诱导的变化的免疫调节。这些研究发现的含义是重要的。通过提供有效的，易于可传递的低成本方法来减轻OW的症状并防止PD的发展或进展，5HT3-RA药物可以大大改善疼痛的治疗方法。