Pharmacologic Approaches to Prescription Opioid Addiction and Relapse Prevention

处方阿片类药物成瘾和预防复发的药理学方法

基本信息

批准号：
8808757
负责人：
JACK BERGMAN
金额：
$ 47.39万
依托单位：
MCLEAN HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-03-01 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8808757
关键词：
Absence of pain sensation Address Agonist Analgesics Behavior Behavioral Biological Assay Buprenorphine Butorphanol Chronic Clinical Complex Counseling Cues Data Dose Drug Addiction Epidemic Exposure to Fentanyl Food Goals Health Heroin Heroin Dependence Human Injection of therapeutic agent Investigation Knowledge Laboratory Animals Maintenance Maintenance Therapy Methadone Modification Monkeys Naltrexone Nociception Opiate Addiction Opioid Opioid Analgesics Oxycodone Pain management Performance Pharmaceutical Preparations Pharmacotherapy Procedures Public Health Recording of previous events Regimen Relapse Research Research Design Self Administration Solid Stimulus Therapeutic Treatment Protocols base clinically relevant comparative compare effectiveness disorder later incidence prevention dosage drug maintenance drug seeking behavior improved nonhuman primate novel pre-clinical prescription opioid prescription opioid abuse programs research study response time interval

项目摘要

DESCRIPTION (provided by applicant): Abuse of prescription opioids such as oxycodone has risen dramatically throughout the last decade and is considered a public health problem of epidemic proportion. Treatment options for prescription opioid addiction are similar to those for heroin, and most frequently incorporate maintenance pharmacotherapy with methadone, buprenorphine, or naltrexone. There is, however, insufficient information to evaluate the clinical utility of either agonist-based or antagonist-based pharmacotherapies for prescription opioid addiction. Moreover, although relapse to prescription opioids is well-documented in human abusers, there is almost no information comparing the effectiveness of agonist or antagonist maintenance regimens in reducing relapse to drug seeking in either humans or laboratory animals. To address this gap in knowledge, we will study how chronic exposure to maintenance pharmacotherapies modifies the relapse-related priming effects of prescription opioids and drug-paired environmental stimuli in nonhuman primates. Our research plan is based on solid preliminary data and previous findings suggesting that the ability of prescription opioids to induce relapse-related behavior during maintenance therapy depends critically on the maintenance drug and the agonist efficacy of the prescription opioid. In our proposed studies, we will use a novel drug/food choice procedure to determine the ability of selected prescription opioids to induce drug-seeking behavior in monkeys with prior histories of persistent oxycodone self-administration before, during and after chronic maintenance regimens with methadone, buprenorphine or naltrexone. These investigations will provide needed preclinical data with direct relevance for understanding pharmacological and behavioral factors that influence relapse vulnerability under different therapeutic maintenance conditions. Our studies also will incorporate a novel performance- based assay to determine threshold values for thermal nociception. We will use this assay to address the complex and clinically difficult issue of changes in the anti-nociceptive effects of prescription opioids before, during and after different maintenance regimens. The impact of our proposed research lies in its ability to provide preclinical information that ultimately can improve the management of prescription opioid addiction and relapse as well as provide guidance regarding the clinical use of prescription opioids for pain management during and after opioid agonist and antagonist maintenance regimens.

描述（由申请人提供）：在过去十年中，羟考酮等处方阿片类药物的滥用急剧增加，并被认为是一个流行病程度的公共卫生问题。处方阿片类药物成瘾的治疗方案与海洛因相似，最常见的是美沙酮、丁丙诺啡或纳曲酮的维持药物治疗。然而，没有足够的信息来评估基于激动剂或基于拮抗剂的药物疗法对处方阿片类药物成瘾的临床效用。此外，尽管在人类滥用者中处方阿片类药物复发的情况已有充分记录，但几乎没有信息比较激动剂或拮抗剂维持方案在减少人类或实验动物中药物寻求复发方面的有效性。为了解决这一知识差距，我们将研究长期接受维持性药物治疗如何改变非人类灵长类动物中处方阿片类药物和药物配对环境刺激的复发相关启动效应。我们的研究计划基于可靠的初步数据和先前的研究结果，表明处方阿片类药物在维持治疗期间诱导复发相关行为的能力主要取决于维持药物和处方阿片类药物的激动剂功效。在我们提出的研究中，我们将使用一种新的药物/食物选择程序来确定选定的处方阿片类药物在美沙酮长期维持方案之前、期间和之后对有持续羟考酮自我给药史的猴子诱导寻药行为的能力、丁丙诺啡或纳曲酮。这些研究将提供所需的临床前数据，与了解在不同治疗维持条件下影响复发易感性的药理学和行为因素直接相关。我们的研究还将采用一种新颖的基于性能的测定法来确定热伤害感受的阈值。我们将使用该测定来解决处方阿片类药物在不同维持方案之前、期间和之后的抗伤害作用变化这一复杂且临床上困难的问题。我们提出的研究的影响在于它能够提供临床前信息，最终可以改善处方阿片类药物成瘾和复发的管理，并为在阿片类药物激动剂和拮抗剂维持方案期间和之后使用处方阿片类药物进行疼痛管理提供指导。