Effects of naltrexone on response to intravenous cocaine, hydromorphone and their combination in humans

Sharon L. Walsh, John T. Sullivan, Kenzie L. Preston, Jane E. Garner, George Bigelow

Research output: Contribution to journalArticle

Abstract

This study evaluated the effects of i.v. cocaine, hydromorphone and their combination, and assessed the ability of oral naltrexone, an opioid antagonist, to modulate these effects. Volunteers with cocaine and heroin abuse histories (n = 8) participated in this placebo-controlled, cross-over study while residing on a closed research unit. Daily treatment with capsules containing placebo or naltrexone in ascending doses (3.125, 12.5, 50 and 200 mg) were given for 7-day periods. In thrice weekly experimental sessions, cocaine, hydromorphone and their combination were given in random order. Drug doses were given in an ascending order 1 hr apart as follows: cocaine at 0, 20 and 40 mg, hydromorphone at 0, 1.5 and 3.0 mg, and the combination of 0 and 0 mg, 20 mg cocaine and 1.5 mg hydromorphone and 40 mg cocaine and 3.0 mg hydromorphone. Hydromorphone and cocaine produced distinct pharmacodynamic profiles, and the combination produced effects similar to both drugs. In some cases, the magnitude of effects produced by the combination was greater than that produced by either drug alone. Naltrexone produced dose-related blockade of hydromorphone effects, but did not alter any of the physiological or subjective effects of cocaine. All naltrexone doses partially attenuated the effects of the combination and this appeared to be attributable to selective opioid blockade. These data do not support the use of naltrexone as a treatment for cocaine abuse, but suggest it may be useful for treating patients with concurrent cocaine and heroin abuse.

Original languageEnglish (US)
Pages (from-to)524-538
Number of pages15
JournalJournal of Pharmacology and Experimental Therapeutics
Volume279
Issue number2
StatePublished - Nov 1996

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Hydromorphone
Naltrexone
Cocaine
Cocaine-Related Disorders
Heroin Dependence
Placebos
Pharmaceutical Preparations
Aptitude
Narcotic Antagonists
Cross-Over Studies
Opioid Analgesics
Capsules
Volunteers
Therapeutics

ASJC Scopus subject areas

  • Pharmacology

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Effects of naltrexone on response to intravenous cocaine, hydromorphone and their combination in humans. / Walsh, Sharon L.; Sullivan, John T.; Preston, Kenzie L.; Garner, Jane E.; Bigelow, George.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 279, No. 2, 11.1996, p. 524-538.

Research output: Contribution to journalArticle

Walsh, Sharon L. ; Sullivan, John T. ; Preston, Kenzie L. ; Garner, Jane E. ; Bigelow, George. / Effects of naltrexone on response to intravenous cocaine, hydromorphone and their combination in humans. In: Journal of Pharmacology and Experimental Therapeutics. 1996 ; Vol. 279, No. 2. pp. 524-538.
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