Buprenorphine's physical dependence potential: Antagonist-precipitated withdrawal in humans

Thomas Eissenberg, Mark K. Greenwald, Rolley E. Johnson, Ira A. Liebson, George Bigelow, Maxine L Stitzer

Research output: Contribution to journalArticle

Abstract

Buprenorphine is a partial mu opioid agonist with demonstrated efficacy in the treatment of opioid dependence. One potential advantage of buprenorphine over full mu opioid agonists is its reported low physical dependence profile. This study systematically examined physical dependence produced by maintenance with a clinically relevant dose of buprenorphine using antagonist challenge procedures. In this residential laboratory study, eight opioid-dependent volunteers maintained on 8 mg/ day of sublingual buprenorphine were each challenged on independent occasions with placebo, i.m. naloxone (0.3, 1.0, 3.0 and 10.0 mg/70 kg) and p.o. naltrexone (0.3,1.0 and 3.0 mg/70 kg) 14 hr after their daily buprenorphine dose using a repeated measures, cross-over design. Both naloxone and naltrexone precipitated time- and dose-dependent withdrawal, as evidenced by changes in subject-rated, observer-rated and physiological measures. Significant precipitated withdrawal occurred at 3.0 and 10 mg/70 kg i.m. of naloxone and 3.0 mg/70 kg p.o. of naltrexone. These results indicate that buprenorphine maintenance produces physical dependence and that i.m. naloxone and p.o. naltrexone produce equivalent effects in withdrawal precipitation under these conditions. Findings have implications for selection of antagonist doses for use in formulating combination agonist/antagonist medications and for use in transition of drug abusers from buprenorphine to antagonist maintenance therapies.

Original languageEnglish (US)
Pages (from-to)449-459
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume276
Issue number2
StatePublished - Feb 1996

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Buprenorphine
Naltrexone
Naloxone
Opioid Analgesics
Drug Users
Cross-Over Studies
Volunteers
Placebos
Maintenance

ASJC Scopus subject areas

  • Pharmacology

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Buprenorphine's physical dependence potential : Antagonist-precipitated withdrawal in humans. / Eissenberg, Thomas; Greenwald, Mark K.; Johnson, Rolley E.; Liebson, Ira A.; Bigelow, George; Stitzer, Maxine L.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 276, No. 2, 02.1996, p. 449-459.

Research output: Contribution to journalArticle

Eissenberg, Thomas ; Greenwald, Mark K. ; Johnson, Rolley E. ; Liebson, Ira A. ; Bigelow, George ; Stitzer, Maxine L. / Buprenorphine's physical dependence potential : Antagonist-precipitated withdrawal in humans. In: Journal of Pharmacology and Experimental Therapeutics. 1996 ; Vol. 276, No. 2. pp. 449-459.
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