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

基本信息

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
项目类别：
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

项目摘要

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近年来，50 岁以上的成年人患阿片类药物使用障碍 (OUD) 的人数激增。中年和老年人中 OUD 的增加是显着且令人震惊的趋势。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（Percocet™ 和 Oxycontin™）始终属于其中。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。尽管羟考酮有被滥用的可能性，但它对于减轻急性疼痛非常有效。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。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，是神经肽催产素所没有的鼻内给药。公认的成瘾潜力，同时具有镇痛作用。表明催产素与阿片类药物合用也可能降低阿片类药物的增强作用。此外，动物和人类的证据也支持这一点。与成瘾和慢性疼痛相关的共同的大脑结构和功能变化，这可能是接受催产素的个体也能很好地耐受催产素的剂量。根据这一证据，我们建议催产素可显着改善 OUD 的症状。减少阿片类药物的滥用倾向并减少 30 名 55-75 岁的健康志愿者。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、受试者体内实验室研究中。额定滥用倾向以及心血管和呼吸系统反应将在 5 年内反复评估还将收集给药后数小时的疼痛测量结果，包括标准化实验。疼痛电池（即，热和机械测试的感官测试）这项研究具有巨大的定量性。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该项目的结果也将促进对疼痛风险较高的成年人的科学认识。我们的多学科团队致力于研究滥用可能性与疼痛之间联系的行为机制。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）人类滥用药物的药物管理和滥用倾向测试 (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。