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 阿片类药物的使用是美国发病率和死亡率的一个主要来源，是一个紧迫的公共卫生问题 危机。近年来，患有阿片类药物使用障碍 (OUD) 的 50 岁以上成年人激增，这是一种 显着且令人震惊的趋势正在增加。中年和老年人中 OUD 的增加部分是由于 由于老年人口中疼痛、手术和身体疾病的发生率很高，因此需要阿片类药物处方 药物，包括羟考酮。羟考酮（Percocet™ 和 Oxycontin™）一直是 最广泛用于治疗疼痛的药物，但也是最广泛滥用并导致过量死亡的药物。 尽管羟考酮可能被滥用，但它对于减轻急性疼痛非常有效。有紧急情况 需要采取干预措施来保留羟考酮的镇痛特性，同时减少其滥用可能性。一个 有希望的疼痛管理辅助治疗选择，同时可以减少滥用 阿片类药物的潜力在于鼻内施用神经肽催产素。催产素没有 公认的成瘾潜力，同时具有镇痛特性。临床前证据 表明催产素与阿片类药物联合使用可能会降低阿片类药物的增强作用。还有催产素 减少人类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同的大脑结构和功能变化，这可能是 由催产素给药调节。接受催产素剂量的个体也能很好地耐受 OUD 药物（例如美沙酮）。基于这一证据，我们建议催产素将显着 减少阿片类药物的滥用倾向并减少实验疼痛。 30名健康的55-75岁志愿者 一些阿片类药物经验者会在口服羟考酮后不久自行注射 48 IU 鼻内催产素（或安慰剂） （0、2.5、5.0 mg）在一项双盲、随机、安慰剂对照、受试者内实验室研究中。主题- 额定滥用倾向以及心血管和呼吸系统反应将在 5 年内反复评估 给药后数小时。还将收集疼痛测量数据，包括标准化实验 疼痛电池（即，带有热和机械测试的定量感官测试）。这项研究具有巨大的 检查鼻内催产素作为减少阿片类药物有前途的药物对公共健康的潜在影响 成瘾潜力并产生阿片类药物节约作用，同时有效减轻疼痛，这可以大大减少 推进药物治疗领域并开辟新的治疗选择，特别是针对中年和老年人 可能面临更高疼痛风险的成年人。该项目的结果还将促进对以下问题的科学理解： 滥用潜力与疼痛之间联系的行为机制。我们的多学科团队是 非常适合解决拟议的目标，具有以下方面的专业知识：（i）鼻内催产素管理（ii）人类 药物管理和滥用药物滥用倾向测试 (iii) 阿片类药物管理和实验性疼痛 测试（iv）多模式疼痛评估和（v）老化。