Gender effects on persistent cerebral metabolite changes in the frontal lobes of abstinent cocaine users

Am J Psychiatry. 1999 May;156(5):716-22. doi: 10.1176/ajp.156.5.716.


Objective: Previous studies found functional changes in the frontal brain region and regions with projections to the frontal lobe in cocaine users. The aim of this study was to investigate persistent neurochemical changes in the frontal lobes of subjects with a history of crack cocaine dependence and to determine whether these changes are different in male and female users.

Method: The frontal gray and white matter of 64 young asymptomatic and abstinent (> 5 months) cocaine users (34 male and 30 female) and 58 healthy comparison subjects without a history of drug abuse was evaluated with localized proton magnetic resonance spectroscopy (1H-MRS).

Results: Two-way analysis of variance showed significant cocaine effects on the concentration of frontal gray matter N-acetyl compounds, on the ratio of frontal white matter N-acetyl compounds to creatine levels, on frontal gray and white matter myoinositol levels, and on the ratio of myoinositol to creatine. Significant gender effects were observed for frontal gray matter choline-containing compounds, the ratio of choline-containing compounds to creatine, and the percentage of CSF in both gray and white matter. Interaction effects of cocaine and gender were observed for creatine, N-acetyl/creatine ratio, and myoinositol/creatine ratio in frontal white matter.

Conclusions: Cocaine use is associated with neuronal injury (with decreased N-acetyl compounds) in the frontal cortex and glial activation (with increased myoinositol) in both frontal gray and white matter. In the frontal lobe, cocaine affects male users differently than female users. Future studies on the effects of cocaine abuse should control for the effects of gender-specific neurotoxicity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Analysis of Variance
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / cerebrospinal fluid
  • Aspartic Acid / metabolism
  • Central Nervous System Diseases / chemically induced
  • Central Nervous System Diseases / metabolism
  • Choline / analysis
  • Choline / cerebrospinal fluid
  • Choline / metabolism
  • Cocaine-Related Disorders / cerebrospinal fluid
  • Cocaine-Related Disorders / complications
  • Cocaine-Related Disorders / metabolism*
  • Crack Cocaine / adverse effects
  • Creatine / analysis
  • Creatine / metabolism
  • Female
  • Frontal Lobe / chemistry
  • Frontal Lobe / drug effects
  • Frontal Lobe / metabolism*
  • Glutamates / analysis
  • Glutamates / cerebrospinal fluid
  • Glutamates / metabolism
  • Glutamine / analysis
  • Glutamine / cerebrospinal fluid
  • Glutamine / metabolism
  • Humans
  • Inositol / analysis
  • Inositol / metabolism
  • Magnetic Resonance Spectroscopy
  • Male
  • Sex Factors


  • Crack Cocaine
  • Glutamates
  • Glutamine
  • Aspartic Acid
  • Inositol
  • N-acetylaspartate
  • Creatine
  • Choline