The potential of oxytocin to reduce opioid abuse liability and pain among older adults

催产素降低老年人阿片类药物滥用倾向和疼痛的潜力

• 批准号: 10667718
• 负责人: Meredith Berry
• 金额: $ 22.88万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10667718
• 关键词: Absence of pain sensation; Acute Pain; Address; Adult; Age; Aging; Analgesics; Animal Model; Animals; Behavioral Mechanisms; Biochemistry; Brain; Brain region; Cardiovascular system; Dose; Double-Blind Method; Drug Prescriptions; Elderly; Future; Health; Heroin; Hour; Human; Individual; Inflammation; Intervention; Intranasal Administration; Intravenous; Laboratory Study; Link; Literature; Measures; Mechanics; Mediator; Methadone; Morbidity - disease rate; Morphine; Mus; Neurons; Neuropeptides; Operative Surgical Procedures; Opioid; Oral; Oxycodone; Oxytocin; Pain; Pain Measurement; Pain management; Pathway interactions; Patients; Percocet; Pharmaceutical Preparations; Pharmacotherapy; Placebo Control; Placebos; Plasma; Population; Prevalence; Property; Public Health; Randomized; Rattus; Reducing Agents; Research; Rewards; Scientific Advances and Accomplishments; Self Administration; Sensory; Source; Standardization; Stimulus; Stress; Structure; Substance Abuse Detection; System; Testing; abuse liability; addiction; addiction liability; analog; antinociception; behavioral economics; chronic pain; conditioned place preference; endogenous opioids; experience; high risk; human model; human old age (65+); medication for opioid use disorder; middle age; mortality; multidisciplinary; multimodality; neurobiological mechanism; novel; novel therapeutics; opioid abuse; opioid misuse; opioid mortality; opioid sparing; opioid use; opioid use disorder; overdose death; pain model; pain reduction; pain sensitivity; pre-clinical; prescription opioid; prescription opioid addiction; preservation; prevent; respiratory; response; substance use treatment; trend; volunteer

ABSTRACT Opioid use is a major source of morbidity and mortality in the U.S. and represents an urgent public health crisis. In recent years, a surge of adults over the age of 50 have developed opioid use disorder (OUD), a significant and alarming trend that is increasing. Increases in OUD in mid-life and older adults is partially due to high rates of pain, surgery, and physical ailments in aging populations that necessitate opioid prescription medications, including oxycodone. Oxycodone (in Percocet™ and Oxycontin™) is consistently among the medications most widely prescribed for pain, but is also most widely abused and involved in overdose deaths. Despite its potential for abuse, oxycodone can be highly effective for reducing acute pain. There is an urgent need for interventions that preserve the analgesic properties of oxycodone while curtailing its abuse potential. A promising adjunct treatment option for pain management, that could simultaneously reduce the abuse potential of opioids, is intranasal administration of the neuropeptide oxytocin. Oxytocin has no recognized addiction potential, and simultaneously has analgesic properties. Preclinical evidence suggests that oxytocin co-administered with opioids may reduce opioid reinforcing effects. Oxytocin also decreases experimental pain in human and animal models. Further, evidence in animals and humans support the shared brain structure and function changes associated with both addiction and chronic pain, which may be modulated by oxytocin administration. Doses of oxytocin are also well-tolerated by individuals receiving medications for OUD (e.g., methadone). Based on this evidence, we propose that oxytocin will significantly reduce abuse liability of opioids and reduce experimental pain. Thirty healthy 55-75 year old volunteers with some opioid experience will self-administer 48 IUs of intranasal oxytocin (or placebo) shortly after oral oxycodone (0, 2.5, 5.0 mg) in a double-blind, randomized, placebo-controlled, within-subjects laboratory study. Subject- rated abuse liability and cardiovascular and respiratory responses will be assessed before and repeatedly for 5 hours following drug administration. Pain measures will also be collected, including a standardized experimental pain battery (i.e., quantitative sensory testing with thermal and mechanical testing). This study has tremendous potential for public health impact in examining intranasal oxytocin as a promising agent for reducing opioid addictive potential and producing opioid-sparing effects, while effectively reducing pain, which could substantially advance the field of pharmacotherapy and carve out a novel treatment option, specifically in mid-life and older adults who may be at higher risk for pain. Results from this project will also advance scientific understanding of behavioral mechanisms underlying the link between abuse potential and pain. Our multidisciplinary team is well-suited to address the proposed aims with expertise in (i) intranasal oxytocin administration (ii) human drug administration and abuse liability testing of drugs of abuse (iii) opioid administration and experimental pain testing (iv) multi-modal pain assessments and (v) aging.

抽象的 阿片类药物使用是美国发病率和死亡率的主要来源，代表着紧急的公共卫生 危机。近年来，50岁以上的成年人激增了阿片类药物使用障碍（OUD），A 正在增加的巨大趋势正在增加。中年和老年人的OUD增加是部分 由于衰老人群的疼痛，手术和身体疾病的高率，需要阿片类药物处方 药物，包括羟考酮。羟考酮（在Percocet™和OxyContin™中）始终是 药物最广泛地处方疼痛，但也受到最广泛滥用，涉及过量死亡。 尽管有滥用的潜力，但羟考酮仍可以非常有效地减轻急性疼痛。有紧急 需要进行干预措施，以保留氧气的镇痛性能，同时减少其滥用潜力。一个 有希望的疼痛管理辅助治疗选择，这可以简单地减少滥用 阿片类药物的潜力是鼻内施用神经肽催产素。催产素没有 公认的成瘾潜力，仅具有镇痛特性。临床前证据 表明与阿片类药物共同采用的氧加毒素可能会降低阿片类药物增强作用。催产素也是如此 减少人和动物模型的实验疼痛。此外，动物和人类的证据支持 与成瘾和慢性疼痛相关的共享大脑结构和功能变化，这可能是 由氧加毒素给药调节。剂量的氧加毒素也受到接受的人的耐受性 OUD的药物（例如Metagadone）。基于这些证据，我们建议氧气将显着 减少阿片类药物的滥用责任并减轻实验性疼痛。 30岁的55-75岁志愿者 一些阿片类药物的经验将在口服羟考酮之后不久自我辅助48鼻内催产素（或安慰剂） （0，2.5，5.0 mg）在双盲，随机，安慰剂对照的，受试者内实验室研究中。主题- 额定滥用责任以及心血管和呼吸反应将在5之前进行评估5 药物管理后的几个小时。还将收集疼痛度量，包括标准化的实验 疼痛电池（即通过热和机械测试进行定量感觉测试）。这项研究有很大的 在检查鼻内催产素作为减少OOID的有前途的药物时，公共卫生可能会影响公共卫生的潜力 加性潜力和产生oioid的效果，同时有效减轻疼痛，这可能会大大减轻 推进药物治疗领域，并找到一种新型的治疗选择，特别是在中年和年龄较大的情况下 可能面临疼痛风险更高的成年人。该项目的结果也将提高对科学理解 滥用潜力与痛苦之间联系的行为机制。我们的多学科团队是 非常适合以（i）鼻内催产素给药（II）人类的专业知识来解决所提出的目标 药物管理和虐待责任测试滥用药物（III）阿片类药物给药和实验疼痛 测试（IV）多模式疼痛评估和（v）衰老。