Mifepristone for the Prevention of Relapses of Alcohol Drinking

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