Document Detail

Opioid physical dependence development in humans: effect of time between agonist pretreatments.
MedLine Citation:
PMID:  7871065     Owner:  NLM     Status:  MEDLINE    
We examined the effect of morphine pretreatment spacing on intensity of subsequent precipitated withdrawal response to test the hypothesis that withdrawal intensity would be inversely related to pretreatment spacing. Subjects were ten nondependent male volunteers who reported using opioids an average of 2.5 times per week. Three IM morphine injections (each 18 mg/70 kg) were administered during each of four experimental conditions. The experimental conditions involved spacing injections at 12-, 24-, 48- or 72-h intervals. Naloxone (10 mg/70 kg IM) was administered 24 h after the last morphine exposure. A comparison condition was included in which a naloxone challenge was given at 24 h following a single IM morphine pretreatment (18 mg/70 kg). Subject rated measures of symptoms and observer-rated measures of signs indicated that withdrawal intensity was inversely related to the morphine spacing interval and in particular that intensity of withdrawal precipitated after three pretreatments spaced at 12-h intervals was greater than that precipitated after a single morphine pretreatment. Physiological data supported a more intense withdrawal response in the 12-h spacing condition and provided evidence of overshoot on blood pressure and skin temperature measures. These findings are pertinent to the transition between acute and chronic physical dependence; they suggest that there is a temporal window during which repeated opioid administrations result in escalation of physical dependence but that dependence levels after widely spaced multiple exposures may be no greater than after a single exposure.
K C Kirby; M L Stitzer
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Psychopharmacology     Volume:  112     ISSN:  0033-3158     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  1993  
Date Detail:
Created Date:  1995-03-29     Completed Date:  1995-03-29     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  GERMANY    
Other Details:
Languages:  eng     Pagination:  511-7     Citation Subset:  IM    
Department of Mental Health Sciences, Hahnemann University School of Medicine, Philadelphia, PA 19102-1192.
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MeSH Terms
Blood Pressure / drug effects
Heart Rate / drug effects
Morphine Dependence / psychology
Naloxone / pharmacology
Opioid-Related Disorders / psychology*
Pupil / drug effects
Skin Temperature / drug effects
Substance Withdrawal Syndrome / psychology
Time Factors
Grant Support
Reg. No./Substance:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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