Buprenorphine, morphine and naloxone effects during ascending morphine maintenance in humans

Kory J. Schuh, Sharon L. Walsh, George E. Bigelow, Kenzie L. Preston, Maxine L. Stitzer

Research output: Contribution to journalArticlepeer-review

Abstract

One purpose of this study was to characterize the acute effects of the partial μ-opioid agonist buprenorphine administered to human subjects undergoing maintenance treatment with ascending doses of morphine. A second purpose was to examine the development of tolerance, cross-tolerance and physical dependence under the same morphine maintenance conditions. Six opioid-dependent volunteers were treated chronically with ascending morphine doses of 15, 30, 60 and 120 mg/day. Each morphine dosing level was maintained for 2 weeks, with test drugs administered during the second week of maintenance on each morphine dose. Both morphine (30 mg i.m.) and buprenorphine (6 mg i.m.) constricted pupils and produced reports of opioid- like subjective effects. The magnitude of these effects was inversely related to the morphine maintenance dose, with no effects being detected at higher maintenance levels. Naloxone (0.3 mg) produced little effect at lower morphine maintenance doses but precipitated withdrawal at higher maintenance doses. Buprenorphine failed to precipitate withdrawal even when subjects were treated with 120 mg/day morphine. These findings indicate that dose-dependent tolerance to morphine, cross-tolerance to buprenorphine and physical dependence develop during morphine maintenance. The finding that buprenorphine does not act as an antagonist under these dosing conditions further supports the clinical observation that there are conditions under which patients dependent on short-acting opioids can be comfortably transferred directly to buprenorphine maintenance treatment.

Original languageEnglish (US)
Pages (from-to)836-846
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume278
Issue number2
StatePublished - Aug 1996

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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