Pharmacologic Approaches to Prescription Opioid Addiction and Relapse Prevention

描述（由申请人提供）：处方阿片类药物（如羟考酮）的滥用在过去十年中急剧上升，被认为是流行病比例的公共卫生问题。处方阿片类药物成瘾的治疗选择与海洛因相似，最常见的是美沙酮、丁丙诺啡或纳洛酮的维持药物治疗。然而，没有足够的信息来评价基于激动剂或基于拮抗剂的药物治疗处方阿片类药物成瘾的临床效用。此外，虽然处方阿片类药物复发在人类滥用者中有充分的记录，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室动物药物寻求复发方面的有效性。为了解决这一知识差距，我们将研究长期暴露于维持药物治疗如何改变处方阿片类药物和药物配对环境刺激在非人灵长类动物中的复发相关启动效应。我们的研究计划是基于坚实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疗效。在我们拟定的研究中，我们将使用一种新的药物/食物选择程序，以确定选定处方阿片类药物在美沙酮、丁丙诺啡或纳洛酮长期维持治疗方案之前、期间和之后，诱导具有持续性羟考酮自我给药既往史的猴中的觅药行为的能力。这些研究将提供所需的临床前数据，这些数据与了解在不同治疗维持条件下影响复发脆弱性的药理学和行为因素直接相关。我们的研究也将结合一种新的性能为基础的测定，以确定阈值的热伤害感受。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性作用的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其提供临床前信息的能力，这些信息最终可以改善处方阿片类药物成瘾和复发的管理，并为阿片类药物激动剂和拮抗剂维持方案期间和之后的处方阿片类药物疼痛管理的临床使用提供指导。

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.