The partial opioid agonist, buprenorphine, protects against lethal effects of cocaine

J. M. Witkin, R. E. Johnson, J. H. Jaffe, S. R. Goldberg, N. A. Grayson, K. C. Rice, J. L. Katz

Research output: Contribution to journalArticlepeer-review

Abstract

Buprenorphine (0.3-3.0 mg/kg) produced dose-dependent protection against the lethal effects of cocaine in mice. The (+)-enantiomer of buprenorphine did not protect up to doses over 100 times greater than the lowest effective dose of its (-)-enantiomer. The protective effects were also produced by the opioid agonists morphine and methadone, but not by the opioid antagonist, naltrexone. Low doses of naltrexone (0.3-1.0 mg/kg) blocked the protective effects of buprenorphine. Protection conferred by buprenorphine was not observed in CXBK mice, a recombinant inbred strain relatively devoid of mu-opioid receptors. Thus, buprenorphine appears to protect against the lethal effects of cocaine by a process mediated by mu-opioid receptors. The present results should provide some additional safety assurance in future clinical trials with buprenorphine, especially in outpatient trials where cocaine abuse may continue along with treatment.

Original languageEnglish (US)
Pages (from-to)177-184
Number of pages8
JournalDrug and Alcohol Dependence
Volume27
Issue number2
DOIs
StatePublished - 1991

Keywords

  • buprenorphine
  • cocaine
  • convulsions
  • CXBK mice
  • lethality
  • methadone
  • morphine

ASJC Scopus subject areas

  • Medicine(all)
  • Behavioral Neuroscience
  • Toxicology
  • Health(social science)

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