Acute physical dependence in humans: Repeated naloxone-precipitated withdrawal after a single dose of methadone

This paper reports the intensity and duration of acute physical dependence precipitated by naloxone administration following a single pre-treatment with the opioid agonist methadone (30 mg/70 kg, i.m.) in six non-dependent human volunteers with histories of prior opioid abuse. In a within-subject cross-over design, challenges of the antagonist naloxone (0.5-1.0 mg, i.m.) were administered at 6, 30 and 54 h, 30 and 54 h, or at only 54 h after methadone pre-treatment. Acute physical dependence, as indicated by physiologic, subjective, and observer rated withdrawal, was seen in all subjects following active naloxone administration, was of nearly uniform intensity for a period of 6-54 h after acute methadone administration, and was not attenuated by prior naloxone administration.