Mifepristone for the Prevention of Relapses of Alcohol Drinking

The goal of this study is to determine if, under stress, alcohol drinking is reduced using mifepristone


Eligibility Criteria:
Inclusion Criteria:

* Male or female, 21 to 65 years of age
* Females must be postmenopausal for at least one year or surgically sterile (proven by medical record)
* Meet criteria for Alcohol Use Disorders (AUD) DSM-5 diagnosis
* Meet drinking criteria (≥3 drinks/day for men; ≥2 drinks /day for women)
* Must be in good health as confirmed by medical history, physical examination, ECG, lab tests
* Participants must be willing to take oral medication and adhere to the study procedures
* Breath alcohol (BrAC) = 0.00 at each visit
* Be able to understand informed consent and questionnaire in English at an 8th grade level

Exclusion Criteria:

* Individuals expressing interest in treatment for alcoholism
* Premenopausal women
* Participants who have significant alcohol withdrawal symptoms, defined as a CIWA-Ar score ≥7
* A repeated positive urine drug screen at baseline for any illegal substance except marijuana.
* Individuals diagnosed with a current "severe" Substance Use Disorder (SUD) diagnosis, other than alcohol or nicotine
* Meet DSM-5 criteria for a diagnosis of schizophrenia, bipolar disorder, or other psychoses
* An active illness within the past six months of the screening visit that meets the DSM-5 criteria for a diagnosis of Major Depressive Disorder (MDD) or Anxiety Disorder, or history of attempted suicide
* Clinically significant medical abnormalities: unstable hypertension, clinically significant abnormal ECG, bilirubin \>150% of the upper normal limit, ALT/AST \>300% the UNL, creatinine clearance ≤60 dl/min
* Current use of psychotropic medications that may have an effect on alcohol consumption
* Current use of any medication involved in the metabolism of alcohol such as aldehyde dehydrogenase (ALDH), alcohol dehydrogenase (ADH) and CYP2E1: Cefamandole, Cefotetan, Sulfamethoxazole, Nitroglycerin, Chlorpropamide, Glyburide.
* Current use of any medication (CYP3A4 inhibitor and substrate) that may interact with mifepristone: cyclosporine, fentanyl, heparin, escitalopram, lovastatin, simvastatin, warfarin
* Current use of any medication (CYP2D6 inhibitor and substrate) that may interact with yohimbine: amitriptyline, doxepin, nortriptyline, venlafaxine
* Medical contraindications for use of mifepristone or yohimbine
* A history of adverse reaction or hypersensitivity to mifepristone or yohimbine
* History of suicide
* History of seizure disorders
* Hypokalemia (low potassium level)\<3.5mEq/L
* Participated in any behavioral and/or pharmacological study within minimum the past 30 days
* Neuroendocrine disorders
* Taking corticosteroids
* Bleeding disorders
* Pre-existing QT prolongation on ECG
* History of porphyria (Mifepristone progesterone receptor antagonist is an inducer of CYP-450 and therefore may have the ability to precipitate or exacerbate attacks of acute porphyria)
* Not willing to engage in protected sex (condom). This risk includes both women and men. Mifepristone long half-life (t1/2 = 18 hrs) and its three main metabolites retain considerable affinity toward human progesterone and glucocorticoid receptors, with serum level similar to the parent mifepristone and there are no studies on the presence of mifepristone or metabolites in semen