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Journal of Pharmacology And Experimental Therapeutics, Vol. 162, Issue 1, 182-189, 1968
Copyright © 1968 by American Society for Pharmacology and Experimental Therapeutics

THE RESPIRATORY EFFECTS OF MORPHINE DURING A CYCLE OF DEPENDENCE

W. R. MARTIN 1, D. R. JASINSKI 1, J. D. SAPIRA 1, H. G. FLANARY 1, O. A. KELLY 1, A. K. THOMPSON 1, and C. R. LOGAN 1

1 National Institute of Mental Health, Addiction Research Center, U. S. Public Health Service, Lexington, Kentucky

The responsiveness of the respiratory center to carbon dioxide was studied through a cycle of morphine dependence in seven subjects. During chronic intoxication with morphine, both respiratory rate and the responsiveness of the respiratory center to CO2 were depressed for over 8 hr after each stabilization dose; however, in the morphine-stabilized patients large additional doses of morphine produced only a liminal degree of additional depression. When subjects were withdrawn from morphine for 16 to 20 hr, the sensitivity of the respiratory center to CO2 was found to he markedly increased above the preaddiction level. The sensitivity of the respiratory center to CO2 returned to control level within 7 weeks after withdrawal and subsequently the respiratory center was found to be hyposensitive to CO2. This hyposensitivity persisted through the 30th week. These data indicate that dependence on morphine produces both an early (primary) and protracted (secondary) abstinence syndrome in man. Further, they are consistent with the homeostatic and redundancy theory of physical dependence.

Submitted on December 20, 1967
Accepted on March 8, 1968




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Copyright © 1968 by the American Society for Pharmacology and Experimental Therapeutics.