Reduced dorsal prefrontal gray matter after chronic ketamine use

Biol Psychiatry. 2011 Jan 1;69(1):42-8. doi: 10.1016/j.biopsych.2010.08.030. Epub 2010 Oct 29.


Background: Use of ketamine as a recreational drug is spreading rapidly among young people all over the world. Epidemiological studies have linked chronic ketamine use with a number of problems, including cognitive impairments, bladder dysfunction, and ketamine-related death. However, little is known about the long-term effects of ketamine use on brain structure and function.

Methods: We used voxel based morphometry in conjunction with statistical parametric mapping on the structural magnetic resonance images of ketamine-dependent (n = 41) and drug-naive control individuals (n = 44) to assess differences in gray matter volume between the two groups.

Results: We observed significant decreases in gray matter volume in bilateral frontal cortex (left superior frontal gyrus and right middle frontal gyrus) of ketamine users in comparison with control subjects (p < .05 corrected for multiple comparisons at cluster-level). Duration of ketamine use was negatively correlated with gray matter volume in bilateral frontal cortex, whereas the estimated total lifetime ketamine consumption was negatively correlated with gray matter volume in left superior frontal gyrus.

Conclusions: We have demonstrated a reduction in frontal gray matter volume in patients after chronic ketamine use. The link between frontal gray matter attenuation and the duration of ketamine use and cumulative doses of ketamine perhaps suggests a dose-dependent effect of long-term use of the drug. Our results have important connotations for the clinical picture that is likely to emerge with the growing recreational use of ketamine and is also relevant to the status of the drug as a model for schizophrenia.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anesthetics, Dissociative / adverse effects*
  • Atrophy / chemically induced*
  • Brain Mapping / methods
  • Female
  • Humans
  • Ketamine / adverse effects*
  • Magnetic Resonance Imaging / methods
  • Male
  • Nerve Fibers, Unmyelinated / drug effects
  • Nerve Fibers, Unmyelinated / pathology*
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / pathology*
  • Substance-Related Disorders / pathology*


  • Anesthetics, Dissociative
  • Ketamine