High-Dose Naloxone Infusions in Normals: Dose-Dependent Behavioral, Hormonal, and Physiological Responses

Martin R. Cohen, Robert M. Cohen, David Pickar, Herbert Weingartner, Dennis L. Murphy

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


Hypotheses of involvement of the endogenous opioid system (EOS) in the regulation of human behavior suggest that functional blockade of the EOS should have behavioral consequences. Clinical administration of the opiate receptor antagonist naloxone hydrochloride, however, has had little or inconsistent behavioral effects in normals. This may be attributable to the use of doses insufficient to yield a complete EOS blockade. To assess this explanation, normals were administered increasing doses of naloxone hydrochloride (0.3 to 4 mg/kg) in a single-blind design. Significant dose-dependent behavioral, hormonal, and physiological effects were found. With increasing doses of naloxone, volunteers demonstrated increasingly dysphoric affects, a deterioration of performance on memory testing, increasing systolic BP and respiratory rate, and increasing plasma cortisol and growth hormone levels. These results are consistent with the expected effects of increasing EOS blockade, and thus suggest that lower doses of naloxone used in previous clinical studies may not have been sufficient to produce a complete EOS blockade. Specifically, they suggest involvement of the EOS in the tonic regulation of normal human mood, memory, BP, respirations, and plasma growth hormone and cortisol levels.

Original languageEnglish (US)
Pages (from-to)613-619
Number of pages7
JournalArchives of General Psychiatry
Issue number6
StatePublished - 1983
Externally publishedYes

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Psychiatry and Mental health


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