Glucocorticoid receptor antagonism decreases alcohol seeking in alcohol-dependent individuals

J Clin Invest. 2015 Aug 3;125(8):3193-7. doi: 10.1172/JCI79828. Epub 2015 Jun 29.


Alcoholism, or alcohol use disorder, is a major public health concern that is a considerable risk factor for morbidity and disability; therefore, effective treatments are urgently needed. Here, we demonstrated that the glucocorticoid receptor (GR) antagonist mifepristone reduces alcohol intake in alcohol-dependent rats but not in nondependent animals. Both systemic delivery and direct administration into the central nucleus of the amygdala, a critical stress-related brain region, were sufficient to reduce alcohol consumption in dependent animals. We also tested the use of mifepristone in 56 alcohol-dependent human subjects as part of a double-blind clinical and laboratory-based study. Relative to placebo, individuals who received mifepristone (600 mg daily taken orally for 1 week) exhibited a substantial reduction in alcohol-cued craving in the laboratory, and naturalistic measures revealed reduced alcohol consumption during the 1-week treatment phase and 1-week post-treatment phase in mifepristone-treated individuals. Mifepristone was well tolerated and improved liver-function markers. Together, these results support further exploration of GR antagonism via mifepristone as a therapeutic strategy for alcoholism.

Trial registration: NCT01548417.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Alcohol Drinking / drug therapy*
  • Alcohol Drinking / physiopathology
  • Alcoholism / drug therapy*
  • Alcoholism / physiopathology
  • Animals
  • Female
  • Hormone Antagonists / administration & dosage*
  • Hormone Antagonists / adverse effects
  • Humans
  • Male
  • Mifepristone / administration & dosage*
  • Mifepristone / adverse effects
  • Rats
  • Receptors, Glucocorticoid / antagonists & inhibitors*


  • Hormone Antagonists
  • Receptors, Glucocorticoid
  • Mifepristone

Associated data