TY - JOUR
T1 - Acute opioid physical dependence in humans
T2 - Effect of naloxone at 6 and 24 hours postmorphine
AU - Heishman, Stephen J.
AU - Stitzer, Maxine L.
AU - Bigelow, George E.
AU - Liebson, Ira A.
N1 - Funding Information:
This research was supported by USPHS Research Grant DA-04011 and Research Training Grant DA-07209 from the National Institute on Drug Abuse. The authors thank Beverly Banks for assistance in conducting the study and Linda Felch for consultation and assistance with data analysis. A preliminary report of this research was presented at the 51st Annual Scientific meeting of the Committee on Problems of Drug Dependence, Inc.; Keystone, CO; June, 1989.
PY - 1990/6
Y1 - 1990/6
N2 - Previous studies in our laboratory have documented the occurrence of naloxone-precipitated opioid abstinence from 45 minutes to 6 hours after acute morphine administration in humans. This study extended the morphine-naloxone interval to 24 hours and examined the effect of repeated naloxone challenges on withdrawal responses. Six male nondependent opiate users participated in eight experimental sessions in which they received single IM injections of morphine (18 mg/70 kg) followed 6 and 24 hours later by challenge sessions with IM placebo or naloxone (10 mg/70 kg). Naloxone challenge at 6 hours postmorphine reversed morphine-induced miosis and subjective reports of opiate symptoms, drug high, good drug effects, and drug liking. At 24 hours postmorphine, naloxone had no effect on these measures, which had returned to premorphine levels. However, at 6 and 24 hours postmorphine, naloxone precipitated subjective symptoms and observer-rated signs of opioid abstinence. When naloxone challenge at 24 hours was preceded by naloxone at 6 hours postmorphine, the magnitude of abstinence symptoms and signs was attenuated. These data suggest that morphine-induced adaptational changes underlying the development of physical dependence persist beyond other measurable agonist effects, and that these changes are disrupted or reversed by repeated antagonist administration.
AB - Previous studies in our laboratory have documented the occurrence of naloxone-precipitated opioid abstinence from 45 minutes to 6 hours after acute morphine administration in humans. This study extended the morphine-naloxone interval to 24 hours and examined the effect of repeated naloxone challenges on withdrawal responses. Six male nondependent opiate users participated in eight experimental sessions in which they received single IM injections of morphine (18 mg/70 kg) followed 6 and 24 hours later by challenge sessions with IM placebo or naloxone (10 mg/70 kg). Naloxone challenge at 6 hours postmorphine reversed morphine-induced miosis and subjective reports of opiate symptoms, drug high, good drug effects, and drug liking. At 24 hours postmorphine, naloxone had no effect on these measures, which had returned to premorphine levels. However, at 6 and 24 hours postmorphine, naloxone precipitated subjective symptoms and observer-rated signs of opioid abstinence. When naloxone challenge at 24 hours was preceded by naloxone at 6 hours postmorphine, the magnitude of abstinence symptoms and signs was attenuated. These data suggest that morphine-induced adaptational changes underlying the development of physical dependence persist beyond other measurable agonist effects, and that these changes are disrupted or reversed by repeated antagonist administration.
KW - Acute physical dependence
KW - Antagonist-precipitated withdrawal
KW - Human subjects
KW - Morphine
KW - Naloxone
KW - Opioid abstinence
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U2 - 10.1016/0091-3057(90)90421-D
DO - 10.1016/0091-3057(90)90421-D
M3 - Article
C2 - 2356213
AN - SCOPUS:0025302671
SN - 0091-3057
VL - 36
SP - 393
EP - 399
JO - Pharmacology, Biochemistry and Behavior
JF - Pharmacology, Biochemistry and Behavior
IS - 2
ER -