Glucocorticoid receptor antagonism decreases alcohol seeking in alcohol-dependent individuals
Leandro F. Vendruscolo, … , Scott Edwards, Barbara J. Mason
Leandro F. Vendruscolo, … , Scott Edwards, Barbara J. Mason
Published June 29, 2015
Citation Information: J Clin Invest. 2015;125(8):3193-3197. https://doi.org/10.1172/JCI79828.
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Glucocorticoid receptor antagonism decreases alcohol seeking in alcohol-dependent individuals

Abstract

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.

Authors

Leandro F. Vendruscolo, David Estey, Vivian Goodell, Lauren G. Macshane, Marian L. Logrip, Joel E. Schlosburg, M. Adrienne McGinn, Eva R. Zamora-Martinez, Joseph K. Belanoff, Hazel J. Hunt, Pietro P. Sanna, Olivier George, George F. Koob, Scott Edwards, Barbara J. Mason

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Figure 2

Mifepristone reduces alcohol-cued craving and drinking in alcoholics while improving liver function.

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Mifepristone reduces alcohol-cued craving and drinking in alcoholics whi...
(A) Visual Analog Scale (VAS) scores of craving severity in response to in vivo alcohol cues. Higher scores indicate greater craving severity. Data represent the estimated marginal mean ± SD. *P < 0.05, mifepristone vs. placebo (linear mixed effects modeling). (B) Total number of alcoholic drinks consumed per week. Data represent the estimated marginal mean ± SEM. *P < 0.05, mifepristone vs. placebo (linear mixed effects modeling). (C) Liver enzymes: GGT, ALT, and AST. Data represent the mean ± SD. Dotplots display individual observations for each condition. *P < 0.05 within-group change from baseline (multivariate analysis of covariance). n = 26 for placebo and n = 28 for mifepristone.