Abuse liability and reinforcing efficacy of oral tramadol in humans

Abstract

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, 3 female) participated in this within-subject, randomized, double blind, placebo-controlled study. Participants completed 14 paired sessions (7 sample, 7 self-administration). During each sample session, an oral dose of tramadol (200, 400 mg), oxycodone (20, 40 mg), codeine (100, 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.

‘Codeine is my companion’: misuse and dependence on codeine containing medicines in Ireland

“…Codeine has an identified abuse potential evident in drug administration research (Babalonis et al 2013), and multiple reportings of case dependence Frei et al 2010). Tolerance develops on repeated administration of codeine within a relatively short time frame, with increasing doses whether legitimate (therapeutic) or intoxicating (non-therapeutic) increasing likelihood of neuro-adaptation and dependence symptomatology (Dobbin & Tobin, 2008;Nielsen et al 2010;Reed et al 2011).…”

Drug-seeking behaviours for codeine-acetaminophen and tramadol-acetaminophen prescriptions: a pilot study

“…Formulary concerns mainly relate to cost. In the last few years, there have been increasing reports of tramadol misuse [13,14], albeit more commonly with high doses [15]. Inevitably, some misuse will likely occur when mood-altering effects are experienced.…”

Tramadol Abuse in a Binge Pattern in a Young Depressed Woman

“…Its antidepressant properties, sustained by the action of the monoaminergic inhibitor, may be an advantage, as the pain, especially if chronic, is often associated with depression [39], but they also imply the risk of complicating the condition of the patients [40]. Besides the opioid dependence, a strong link with the drug could indeed develop, mainly supported by its antidepressant effects and the worsening of depression when trying to stop taking tramadol.…”