Subanesthetic doses of ketamine stimulate psychosis in schizophrenia

Adrienne C. Lahti, Bettylou Koffel, David LaPorte, Carol A. Tamminga

Research output: Contribution to journalArticlepeer-review

444 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)9-19
Number of pages11
Issue number1
StatePublished - Aug 1995


  • Excitatory amino acids
  • Glutamate
  • Ketamine
  • Psychosis
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health


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