Walsh Sharon L, Nuzzo Paul A, Lofwall Michelle R, Holtman Joseph R
Department of Behavioral Sciences, Center on Drug and Alcohol Research, University of Kentucky, 515 Oldham Court, Lexington, KY 40502, USA.
Drug Alcohol Depend. 2008 Dec 1;98(3):191-202. doi: 10.1016/j.drugalcdep.2008.05.007. Epub 2008 Jul 7.
Abuse of prescription opioids has risen precipitously in the United States. Few controlled comparisons of the abuse liability of the most commonly abused opioids have been conducted. This outpatient study employed a double-blind, randomized, within-subject, placebo-controlled design to examine the relative abuse potential and potency of oral oxycodone (10, 20 and 40 mg), hydrocodone (15, 30 and 45 mg), hydromorphone (10, 17.5 and 25mg) and placebo. Healthy adult volunteers (n=9) with sporadic prescription opioid abuse participated in 11 experimental sessions (6.5h in duration) conducted in a hospital setting. All three opioids produced a typical mu opioid agonist profile of subjective (increased ratings of liking, good effects, high and opiate symptoms), observer-rated, and physiological effects (miosis, modest respiratory depression, exophoria and decrements in visual threshold discrimination) that were generally dose-related. Valid relative potency assays revealed that oxycodone was roughly equipotent to or slightly more potent than hydrocodone. Hydromorphone was only modestly more potent (less than two-fold) than either hydrocodone or oxycodone, which is inconsistent with prior estimates arising from analgesic studies. These data suggest that the abuse liability profile and relative potency of these three commonly used opioids do not differ substantially from one another and suggest that analgesic potencies may not accurately reflect relative differences in abuse liability of prescription opioids.
在美国,处方类阿片药物的滥用现象急剧增加。针对最常被滥用的阿片类药物的滥用可能性,几乎未进行过对照研究。这项门诊研究采用双盲、随机、受试者自身对照、安慰剂对照设计,以检验口服羟考酮(10毫克、20毫克和40毫克)、氢可酮(15毫克、30毫克和45毫克)、氢吗啡酮(10毫克、17.5毫克和25毫克)及安慰剂的相对滥用潜力和效力。有偶尔滥用处方类阿片药物情况的健康成年志愿者(n = 9)参与了在医院环境中进行的11次实验环节(每次持续6.5小时)。所有三种阿片类药物均产生了典型的μ阿片受体激动剂特征,包括主观效应(愉悦感、良好效果、兴奋感和阿片样症状评分增加)、观察者评定效应以及生理效应(瞳孔缩小、适度呼吸抑制、外斜视和视觉阈值辨别能力下降),且这些效应通常与剂量相关。有效的相对效力测定表明,羟考酮与氢可酮大致等效或效力略强。氢吗啡酮仅比氢可酮或羟考酮略强(不到两倍),这与先前镇痛研究得出的估计结果不一致。这些数据表明,这三种常用阿片类药物的滥用可能性特征和相对效力彼此之间差异不大,提示镇痛效力可能无法准确反映处方类阿片药物滥用可能性的相对差异。