Onset, magnitude and duration of opioid blockade produced by buprenorphine and naltrexone in humans

Kory J. Schuh, Sharon L. Walsh, Maxine L. Stitzer

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Rationale: One therapeutic benefit of mu opioid agonist or antagonist maintenance is the resultant attenuation of the effects of illicit opioids. It is important to characterize the development and duration of opioid blockade produced by buprenorphine, a novel opioid dependence pharmacotherapy. Objective: This study characterized the ability of buprenorphine to attenuate opioid effects during treatment initiation and discontinuation compared to naltrexone and placebo. Methods: Opioid- experienced volunteers (n = 8) participated in this 10-week, inpatient, double-blind, within-subject, crossover study. Five randomized conditions [buprenorphine (2 and 8 mg, sublingually), naltrexone (25 and 100 mg, PO) and placebo] were each examined during a 2-week period; the test drug was given for 7 days followed by a 7-day placebo wash-out. Cumulative doses of hydromorphone (0, 2 and 4 mg, IM, 45 min apart) were administered thrice- weekly corresponding with treatment and wash-out days 1, 3, and 5; behavioral, physiological and pharmacokinetic measures were collected. Results: Buprenorphine alone produced dose-related prototypic agonist effects during induction (i.e., positive mood, respiratory depression, miosis); tolerance developed only to the subjective effects. Buprenorphine 2 mg partially attenuated the effects of hydromorphone, while nearly complete attenuation was observed with 8 mg that lasted up to 72 h after discontinuation. Both naltrexone doses produced complete hydromorphone blockade after a single dose; blockade of the behavioral, but not physiological, effects persisted for 5 days after discontinuation of 100 mg. Conclusions: These data suggest that 2 mg buprenorphine is a sub-therapeutic maintenance dose, both buprenorphine 8 mg and naltrexone produce immediate and efficacious opioid blockade, and adequate protection against illicit opioids may be achieved with less-than-daily dosing.

Original languageEnglish
Pages (from-to)162-174
Number of pages13
Issue number2
StatePublished - 1999

Bibliographical note

Funding Information:
Jane Garner, Veronica Beverly, Paul Nuzzo and John Yingling for technical services; Iona Johnson for pharmacy services; Mike DiMarino for statistical analyses; and David Ginn, MD, Ira Liebson, MD and the Residential Nursing Staff for medical consultation and supervision. This research was supported by United States Public Health Service Grants DA04011, DA06165, and DA05792, and Training Grant T32-DA07209 from the National Institute on Drug Abuse.


  • Buprenorphine
  • Human
  • Naltrexone
  • Opioid blockade

ASJC Scopus subject areas

  • Pharmacology


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