title: 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.forename: Leandro F
authors.initials: LF
authors.lastname: Vendruscolo
authors.forename: David
authors.initials: D
authors.lastname: Estey
authors.forename: Vivian
authors.initials: V
authors.lastname: Goodell
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Macshane
authors.forename: Marian L
authors.initials: ML
authors.lastname: Logrip
authors.forename: Joel E
authors.initials: JE
authors.lastname: Schlosburg
authors.forename: M Adrienne
authors.initials: MA
authors.lastname: McGinn
authors.forename: Eva R
authors.initials: ER
authors.lastname: Zamora-Martinez
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Belanoff
authors.forename: Hazel J
authors.initials: HJ
authors.lastname: Hunt
authors.forename: Pietro P
authors.initials: PP
authors.lastname: Sanna
authors.forename: Olivier
authors.initials: O
authors.lastname: George
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
authors.forename: Scott
authors.initials: S
authors.lastname: Edwards
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Mason
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000503:physiopathology; D000437:Alcoholism / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D005260:Female; D006727:Hormone Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage* / Q000009:adverse effects; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*
chemical_list: D006727:Hormone Antagonists; D011965:Receptors, Glucocorticoid; D015735:Mifepristone