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 against 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, 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.
Wright
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Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Bigelow
G E
GE
Stitzer
M L
ML
Liebson
I A
IA
D000328:Adult; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology*; D009460:Neurologic Examination; D009293:Opioid-Related Disorders / Q000503:physiopathology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology; D012025:Reflex, Pupillary / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D011957:Receptors, Opioid; D009270:Naloxone; D008691:Methadone