LICIT AND ILLICIT OPIOIDS: COMPARATIVE STUDIES IN HUMANS: STUDY 1

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。流行病学研究报告说，处方阿片类镇痛剂的非医疗使用和转用增加。羟考酮以一系列配方销售，用于治疗急性和慢性疼痛。奥施康定是一种缓释制剂，与速释产品相比，它以更高剂量的制剂上市；由于有报道称，意外上瘾、致命过量和犯罪转移的频率增加，这两种制剂都受到了大量负面宣传。氢可酮是一种相关的半合成阿片类药物，是美国处方最广泛的阿片类止痛药，也是急诊室入院时提到最多的处方阿片类药物。尽管它们在临床上广泛使用，但很少有研究评估这些常用阿片类药物的滥用易感性和临床药理学。该项目将采用受控实验室程序来评估羟考酮和氢可酮在一系列条件下有阿片类药物滥用史的志愿者身上的效果。这项研究将使用随机、安慰剂对照、双盲、受试者内设计。出于安全目的，剂量增加试点评估将在随机测试之前进行。实验1将比较口服羟考酮和氢可酮与氢吗啡酮和安慰剂的效果，氢吗啡酮是一种已知的高滥用潜力的阿片类药物，而安慰剂的剂量范围很大。将收集生理、主观和行为指标，分别评估安全和滥用风险，一系列精神运动和认知任务将评估这些代理人的损害影响。这项研究将对这些广泛使用的制剂在治疗和超治疗剂量下在可能滥用它们的受试者中的相对滥用潜力和安全性提供实质性的新知识。与公众健康相关的信息将包括这些化合物的相对效力和耐受性，以及与这些制剂的安全性、调度和市场营销相关的经验信息

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Epidemiological studies report increasing non-medical use and diversion of prescription opioid analgesics. Oxycodone is marketed in an array of formulations and used for the treatment of acute and chronic pain. Oxycontin¿ is a sustained-release formulation which is marketed in higher dosage formulations compared to immediate release products; both formulations have received substantial negative publicity due to reports of increased frequency of unintentional addiction, fatal overdose and criminal diversion. Hydrocodone, a related semi-synthetic opioid, is the most widely prescribed opioid analgesic in the United States and the most frequently mentioned prescription opioid in emergency room admissions. Despite their widespread clinical use, few studies have evaluated the abuse liability and clinical pharmacology of these commonly used opioids. This project will employ controlled laboratory procedures to evaluate and characterize the effects of oxycodone and hydrocodone in volunteers with histories of opioid abuse under an array of conditions. This study will use a randomized, placebo-controlled, double-blind, within-subject design. Dose rising pilot evaluations will precede randomized testing for safety purposes. Experiment 1 will compare the effects of oral oxycodone and hydrocodone to those of hydromorphone, a mu opioid agonist with known high abuse potential, and placebo over a broad range of doses. Physiological, subjective and behavioral measures will be collected to assess safety and abuse liability, respectively, and a battery of psychomotor and cognitive tasks will assess the impairing effects of these agents. This study will contribute substantial new knowledge about the relative abuse potential and safety of these widely available agents at therapeutic and supratherapeutic doses in a population of subjects who are likely to abuse them. Information relevant to the public health will include the relative potency and tolerability of these compounds, and empirical information relevant to safety, scheduling and marketing of these agent