Megadoses of vitamin C prevent the development of tolerance and physical dependence on morphine in mice

Life Sci. 1983;33 Suppl 1:401-4. doi: 10.1016/0024-3205(83)90527-1.


In mice ascorbate, when co-administered with morphine, suppresses the development of tolerance and physical dependence on the drug, without significantly affecting its analgesic properties as inferred from unaltered ED50 values. The duration of morphine-induced analgesia, however, is progressively reduced with an increase in the amounts of ascorbate. Ascorbate at 1g/kg body weight does not alter the pH of blood, and has no effect on the levels of lipid-peroxides in blood and brain. Studies presented in this paper suggest the potential use of ascorbate in the prevention of development of tolerance in therapeutic applications of narcotics as analgesics. Cultured Neuroblastoma X Glioma hybrid cells (NG 108-15) respond to opiates in two different ways. The rapid receptor mediated inhibition of adenylate cyclase is followed by a long-lived compensatory increase in its activity (1-4). In a recent report (5) we have shown that ascorbate suppresses the delayed etorphine-induced compensatory increase in cAMP levels in NG 108-15 cells without affecting the short-term inhibitory response of cells to the drug. It has been suggested that while the former may be the basis of narcotic dependence and tolerance, the latter is responsible for the analgesic effect. These observations, based on a model system, prompted us to examine the effect of ascorbate on the pharmacological properties of morphine at the organismal level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesia
  • Animals
  • Ascorbic Acid / pharmacology*
  • Drug Tolerance
  • Humans
  • Mice
  • Morphine / pharmacology*
  • Morphine Dependence / physiopathology*
  • Orthomolecular Therapy


  • Morphine
  • Ascorbic Acid