Glucocorticoid receptor antagonism decreases alcohol seeking in alcohol-dependent individuals
Year: 2015
Type: article
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.
DOI: 10.1172/jci79828
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: G1261921749, G131349678, The Role of Brain Stress Systems in the Prefrontal Cortex in Compulsive Drinking, G1372395440, G1567329144, G2078917261, G2338239574, G4308325704, G457648599, G5115796070, G56130422, G5861251585, G7011311937, G738808116, G7636921007, G804542775, G8241516228, G9000099968, G9000217511, G9000264711, G9000312651, CNS Effects of Alcohol: Cellular Neurobiology
OpenAlex ID: W1910403263