The goal of this research is to replicate findings previously conducted in a pilot trial and to understand, mechanistically, the role of stress in the development of AUD pharmacotherapies that target noradrenergic blockade.

16 week, between-subject, double-blind, randomized clinical trial (RCT) with doxazosin (16 mg, or maximum tolerated dose, MTD) compared to placebo in 184 treatment seeking individuals with AUD

Inclusion Criteria:

• Male or female, 18 years of age
• Meet the DSM-5 criteria for AUD
• Desire to reduce or quit alcohol drinking
• Breath alcohol (BrAC) = 0.00 at each visit
• In good health as confirmed by medical history, physical examination and lab tests
• Willing to adhere to the study procedures
• Understand informed consent and questionnaires in English at an 8th grade level

Exclusion Criteria:

• Women who are breastfeeding or /positive urine test for pregnancy
• CrCl<60mL/min
• Suicide attempt in the last three months
• Current diagnosis of other substance disorder other than nicotine as assessed by self-report and urine toxicology screen at baseline
• Current use of medication that may interact with doxazosin and/or yohimbine
• History of allergy to any alpha receptor blockers
• Clinical Institute Withdrawal Assessment for Alcohol revised (CIWA-Ar) score ≥ 8
• Treatment with disulfiram, naltrexone, acamprosate, topiramate within 1 month prior to screening
• Treatment with any alpha-blocker
• Individuals with cardiac heat failure (CHF), as assessed by the medical history, the physical exam and the ECG.
• Baseline hypotension defined as BP reading lower than 90/60 mmHg
• Use of phosphodiesterase inhibitors (PDE5) erectile dysfunction medication