Subanesthetic doses of ketamine stimulate psychosis in schizophrenia

Neuropsychopharmacology. 1995 Aug;13(1):9-19. doi: 10.1016/0893-133X(94)00131-I.


We administered ketamine to schizophrenic individuals in a double-blind, placebo-controlled design using a range of subanesthetic doses (0.1, 0.3, and 0.5 mg/kg) to evaluate the nature, dose characteristics, time course, and neuroleptic modulation of N-methyl-D-aspartate (NMDA) antagonist action on mental status in schizophrenia. Ketamine induced a dose-related, short (< 30 minutes) worsening in mental status in the haloperidol-treated condition, reflected by a significant increase in BPRS total score for the 0.3 mg/kg (p = .005) and 0.5 mg/kg (p = .01) challenges. Positive symptoms (hallucinations, delusions, thought disorder), not negative symptoms accounted for these changes. These ketamine-induced psychotic symptoms were strikingly reminiscent of the subject's symptoms during active episodes of their illness. Results from six patients who were retested in the same design after being neuroleptic-free for 4 weeks failed to indicate that haloperidol blocks ketamine-induced psychosis. Several subjects evidenced delayed or prolonged (8-24 hours) psychotomimetic effects such as worsening of psychosis with visual hallucinations. These data suggest that antagonism of NMDA-sensitive glutamatergic transmission in brain exacerbates symptoms of schizophrenia.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Glutamic Acid / pharmacology
  • Haloperidol / pharmacology
  • Humans
  • Injections, Intravenous
  • Ketamine / therapeutic use*
  • Male
  • Middle Aged
  • Psychoses, Substance-Induced*
  • Schizophrenia / drug therapy*
  • Time Factors


  • Glutamic Acid
  • Ketamine
  • Haloperidol