Supersensitivity to Naloxone following acute morphine pretreatment in humans: behavioral, hormonal and physiological effects

Stephen T. Higgins, Kenzie L. Preston, Edward J. Cone, Jack E. Henningfield, Jerome H. Jaffe

Research output: Contribution to journalArticle

Abstract

The effects of naloxone (10 mg/70 kg) given 6 h following acute exposure to morphine (4, 8, 16 mg/70 kg) were assessed in 5 opiate-abusing volunteers who were not physically dependent upon entering the study. Naloxone increased cortisol plasma levels more following morphine than placebo pretreatment. Naloxone reversed the effects of morphine on pupil diameter and oral temperature and decreased skin temperature as a function of morphine pretreatment. Subjects' ability to detect the effects of naloxone, their scores on an opiate-withdrawal questionnaire, and their visual-analog ratings of 'bad effects', 'chills', 'confused' and 'restlessness' increased when naloxone followed pretreatment with 8 and 16 mg, but not 4 mg, of morphine. Performance on the Digit Symbol Substitution Test was not discernibly affected under any of the dose conditions. Overall, results from the present study provide further evidence in humans that the administration of naloxone shortly following acute morphine pretreatment increases naloxone sensitivity, produces signs and symptoms typical of opiate withdrawal and that these effects are dependent on the dose of morphine administered.

Original languageEnglish (US)
Pages (from-to)13-26
Number of pages14
JournalDrug and alcohol dependence
Volume30
Issue number1
DOIs
StatePublished - Apr 1992

Keywords

  • acute physical dependence
  • behavior
  • cortisol
  • hormones
  • humans
  • morphine
  • naloxone
  • opioids
  • prolactin

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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