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

• 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
• 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

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）：主要研究者是一名新的独立科学家（1 R 01 DA 029078 - 01 A1），他是斯坦福大学的医生和临床研究员。该奖项将提供一段时间的密集研究重点，这将使PI提高他的研究生涯（见研究）。该奖项也将用于促进候选人的发展，以扩大他的潜力，使重大的研究贡献（见候选人）。候选人：PI是一位新的独立科学家（1 R 01 DA 029078 - 01 A1），曾获得NIH职业发展奖资助（K23 GM 071400; NIH临床研究LRP），他将利用K 02奖从事进一步的职业发展活动，以扩大其做出重大研究贡献的潜力。这些活动包括负责任地进行研究的培训，与高级研究人员合作开发新的调查模式，参加会议，进一步研究建议，研究指导以及直接转化为患者护理的高质量研究的出版物。环境：PI的400平方米。英尺人类阿片生理学实验室位于斯坦福大学医学院，这是一个科学活动中心，也是2008年和2011年获奖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功能磁共振成像中心设施有着积极的研究合作，此外还与流行病学和健康研究政策部门的高级科学家保持着持续的关系。这些设施和合作关系使斯坦福大学成为支持该奖项目标的最佳环境。研究人员：目前，阿片类药物是美国医生处方的最常见药物之一，维柯丁（氢可酮/对乙酰氨基酚）是任何类别中最常用的药物。然而，身体依赖（PD），成瘾和阿片类药物戒断（OW）使处方阿片类药物的使用复杂化。在2006年所有12岁及以上的美国人中，13.6%（超过3300万）报告至少有一次使用处方阿片类药物用于非医疗目的，前一年超过1200万，上个月有520万。最近的证据，从研究采用药物遗传学单体型为基础的计算映射的5 HT 3受体与PD和OW。PI初步研究的其他数据表明，5 HT 3受体拮抗剂（RA）可以显着降低人类阿片类药物戒断的客观指标。PI的当前研究将评价5 HT 3-RA用于治疗和预防处方阿片类药物滥用的新适应症。PI实验室的其他研究旨在通过新的方式揭示慢性阿片类药物治疗对人体生理学的影响，包括fMRI和阿片类药物诱导变化的免疫调节。这些研究结果的影响是巨大的。通过提供一种有效、易于交付、低成本的方法来缓解OW的症状并预防PD的发展或进展，5 HT 3-RA药物可以显着改善疼痛的治疗。