NMDA receptor challenge with dextromethorphan - subjective response, neuroendocrinological findings and possible clinical implications

J Neural Transm (Vienna). 2000;107(6):701-14. doi: 10.1007/s007020070071.


Glutamatergic NMDA receptors are believed to play a major role in the pathophysiology of numerous neuropsychiatric disorders including substance use and schizophrenia. Neuropharmacological studies measuring subjective response, psychopathology and biological parameters are helpful in studying pathophysiology of these disorders. We report preliminary data of a placebo-controlled double-blind challenge study in recently detoxified alcoholics (n = 20) and healthy controls (n = 10) using the non-competitive NMDA antagonist dextromethorphan. Findings suggest that dextrometorphan can produce ethanol-like subjective effects in both alcoholics and controls and induce a mild form of craving in alcoholics only. The results of this study give further support to the hypothesis of glutamatergic NMDA receptors mediating much of ethanol's psychotropic effects. Possible clinical implications of these findings are discussed.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alcoholism / drug therapy*
  • Alcoholism / physiopathology*
  • Dextromethorphan / administration & dosage*
  • Dextromethorphan / blood
  • Double-Blind Method
  • Excitatory Amino Acid Antagonists / administration & dosage*
  • Excitatory Amino Acid Antagonists / blood
  • Humans
  • Hydrocortisone / blood
  • Male
  • Middle Aged
  • Neurosecretory Systems / drug effects*
  • Neurosecretory Systems / physiology
  • Prolactin / blood
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Substance Withdrawal Syndrome / drug therapy
  • Substance Withdrawal Syndrome / physiopathology


  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Dextromethorphan
  • Prolactin
  • Hydrocortisone