Abuse liability and reinforcing efficacy of oral tramadol in humans
Abuse liability and reinforcing efficacy of oral tramadol in humans
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DOI：
10.1016/j.drugalcdep.2012.09.018
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发表时间：
2013-04-01
影响因子：
4.2
通讯作者：
Walsh, Sharon L.
中科院分区：
文献类型：
--
作者：
Babalonis, Shanna;Lofwall, Michelle R.;Walsh, Sharon L.
背景：曲马多是一种单胺能再摄取抑制剂，经肝脏代谢为阿片受体激动剂（M1）。这种非典型镇痛药通常被认为具有有限的滥用责任。最近在美国，关于其滥用的报道有所增加，导致一些州的监管更加严格，但不是全国性的。本研究的目的是检查曲马多的相对滥用倾向和加强疗效相比，高（羟考酮）和低疗效（可待因）阿片agonist.Methods：9名健康，非依赖性处方阿片类药物滥用者（6名男性和3名女性）参加了这一内的主题，随机，双盲，安慰剂对照研究。参与者完成了14个配对会话（7个样本和7个自我管理）。在每次采样期间，给予口服剂量的曲马多（200和400 mg）、羟考酮（20和40 mg）、可待因（100和200 mg）或安慰剂，并收集一系列完整的滥用倾向指标。在自我管理会议期间，志愿者有机会工作（通过渐进的比例）的样品剂量或money.Results：所有的活性剂量自我管理，安慰剂产生没有反应。高剂量的曲马多和羟考酮易于自我给药（分别占可用药物的70%和59%）;低剂量和两种可待因剂量维持中等水平的药物服用。所有这三种药物的剂量依赖性增加的措施表明滥用的责任，相对于安慰剂，然而，这些和其他药效学效应的幅度和时间过程不同的定性跨drugs.Conclusions：这项研究表明，像其他μ阿片类药物，更高剂量的曲马多功能作为阿片类药物滥用者，提供新的经验数据监管评估。(C)2012爱思唯尔爱尔兰有限公司保留所有权利。
Background: Tramadol, a monoaminergic reuptake inhibitor, is hepatically metabolized to an opioid agonist (M1). This atypical analgesic is generally considered to have limited abuse liability. Recent reports of its abuse have increased in the U.S., leading to more stringent regulation in some states, but not nationally. The purpose of this study was to examine the relative abuse liability and reinforcing efficacy of tramadol in comparison to a high (oxycodone) and low efficacy (codeine) opioid agonist.Methods: Nine healthy, non-dependent prescription opioid abusers (6 male and 3 female) participated in this within-subject, randomized, double blind, placebo-controlled study. Participants completed 14 paired sessions (7 sample and 7 self-administration). During each sample session, an oral dose of tramadol (200 and 400 mg), oxycodone (20 and 40 mg), codeine (100 and 200 mg) or placebo was administered, and a full array of abuse liability measures was collected. During self-administration sessions, volunteers were given the opportunity to work (via progressive ratio) for the sample dose or money.Results: All active doses were self-administered; placebo engendered no responding. The high doses of tramadol and oxycodone were readily self-administered (70%, 59% of available drug, respectively); lower doses and both codeine doses maintained intermediate levels of drug taking. All three drugs dose-dependently increased measures indicative of abuse liability, relative to placebo; however, the magnitude and time course of these and other pharmacodynamic effects varied qualitatively across drugs.Conclusions: This study demonstrates that, like other mu opioids, higher doses of tramadol function as reinforcers in opioid abusers, providing new empirical data for regulatory evaluation. (C) 2012 Elsevier Ireland Ltd. All rights reserved.