Cognitive impairment after small-dose ketamine isomers in comparison to equianalgesic racemic ketamine in human volunteers

Anesthesiology. 2002 Feb;96(2):357-66. doi: 10.1097/00000542-200202000-00022.


Background: Ketamine is increasingly used in pain therapy but may impair brain functions. Mood and cognitive capacities were compared after equianalgesic small-dose S(+)-, R(-)-, and racemic ketamine in healthy volunteers.

Methods: Twenty-four subjects received intravenous 0.5 mg/kg racemic, 0.25 mg/kg S(+)-, and 1.0 mg/kg R(-)-ketamine in a prospective, randomized, double-blind, crossover study. Hemodynamic variables, mood, and cognitive capacities were assessed for 60 min.

Results: Transient increases in blood pressure, heart rate, and catecholamines were similar after administration of all drugs. At 20 min after injection, subjects felt less decline in concentration and were more brave after S(+)- than racemic ketamine. They reported being less lethargic but more out-of-control after R(-)- than racemic ketamine. Ketamine isomers induced less drowsiness, less lethargy, and less impairment in clustered subjective cognitive capacity than racemic ketamine for the 60-min study. Objective concentration capacity [test time, S(+): 25.4 +/- 15.2 s, R(-): 34.8 +/- 18.4 s, racemic ketamine: 40.8 +/- 20.8 s, mean +/- SD] and retention in primary memory [test time, S(+): 4.6 +/- 1.2 s, R(-): 4.2 +/- 1.4 s, racemic ketamine: 4.0 +/- 1.4 s, mean +/- SD] declined less after S(+)- than either R(-)- or racemic ketamine at 1 min. At 5 min, immediate recall, anterograde amnesia, retention in primary memory, short-term storage capacity, and intelligence quotient were less reduced after the isomers than racemic ketamine. Speed reading and central information flow decreased less after S(+)- than racemic ketamine.

Conclusions: Early after injection, ketamine isomers induce less tiredness and cognitive impairment than equianalgesic small-dose racemic ketamine. In addition, S(+)-ketamine causes less decline in concentration capacity and primary memory. The differences in drug effects cannot be explained by stereoselective action on one given receptor.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Affect / drug effects
  • Amnesia, Anterograde / chemically induced
  • Amnesia, Anterograde / psychology
  • Cognition Disorders / chemically induced*
  • Cognition Disorders / psychology*
  • Cross-Over Studies
  • Double-Blind Method
  • Excitatory Amino Acid Antagonists / adverse effects*
  • Excitatory Amino Acid Antagonists / chemistry
  • Excitatory Amino Acid Antagonists / pharmacokinetics
  • Female
  • Humans
  • Intelligence Tests
  • Ketamine / adverse effects*
  • Ketamine / chemistry
  • Ketamine / pharmacokinetics
  • Male
  • Mental Recall / drug effects
  • Norepinephrine / blood
  • Prospective Studies
  • Psychomotor Performance / drug effects
  • Reading
  • Stereoisomerism


  • Excitatory Amino Acid Antagonists
  • Ketamine
  • Norepinephrine