Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 125, Issue 8, Pages 3193-3197Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI79828
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Funding
- National Institute on Alcohol Abuse and Alcoholism (NIAAA/NIH) [AA012602, AA023152, AA020608, AA022977, AA006420, AA020839]
- Pearson Center for Alcoholism and Addiction Research
- LSUHSC School of Medicine Start-Up Funds
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [K99AA020839, R01AA022977, P60AA006420, R01AA020608, R01AA023152, R01AA012602, P50AA006420, R00AA020839, R01AA021667] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [K99DA037344] Funding Source: NIH RePORTER
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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.
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