The investigators assess whether guanfacine extended release (GXR; 3mg/d) compared with placebo (PBO) will attenuate drinking and drinking-related factors in N=200 men and women with Alcohol Use Disorder (AUD) across 12-weeks.

This is a study to examine the efficacy of guanfacine extended release (GXR) (3mg/d) compared with placebo (PBO) in reducing drinking in N=200 men and women with Alcohol Use Disorder (AUD). The study will be conducted across two sites for 12-weeks. Indiana University will be the primary site and Rutgers University, the secondary site. Participants at both sites will be randomized to either GXR (3mg/d) or placebo (PBO), and titrated to full dose over a three week period. After remaining at full dose for 7 weeks a two week schedule will be used to taper participants off the medication. During the study the investigators will collect brief reports throughout the day and evening of drinking severity, stress, craving, mood, arousal, anxiety, and emotion regulation at weeks 1 and 2 (baseline) and weeks 5 and 6 (steady state). Additionally, blood alcohol concentration (BAC) levels will be collected three times per day for the full 12-weeks. Daily encrypted video recordings will be used to monitor medication compliance, and participants will also take part in twice weekly remote visits to assess safety, vitals, collect urines, monitor alcohol use, and receive weekly Medical Management. It is anticipated that guanfacine will demonstrate greater efficacy in women compared to men with AUD.

Inclusion Criteria:

• be assigned as a biological male or female at birth and identify as such
• meet current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM V) criteria for moderate to severe AUD
• be ≥18 years old and have a body mass index (BMI) of 18-35
• express a desire to quit alcohol as determined by the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES)
• demonstrate a positive urine for alcohol on admission to study procedures
• be able to provide informed verbal and written consent
• be able to read English and complete study evaluations
• be in good health as verified by the intake 1 physical examination

Exclusion Criteria:

• meet criteria for moderate to severe Substance Use Disorder (SUD), excluding alcohol and nicotine
• have a positive screen for substances of abuse, excluding alcohol, nicotine,
• being psychotic or otherwise severely psychiatrically disabled (including suicidal, homicidal, current mania)
• meet criteria for physiological dependence on alcohol requiring medical detoxification
• regular use of medications in the last 6 months that, in the opinion of the site physician may be contraindicated with GXR and be potentially harmful to the participant
• be pregnant or breast feeding
• be using monophasic contraceptives
• have cardiovascular disease including high blood pressure,
• be hypotensive with sitting blood pressure below 100/50 mmHG
• have bradycardia with a sitting heart rate (HR) of <60 bpm
• show EKG evidence of any clinically significant conduction abnormalities, including a Bazett's corrected QT interval (QTc) >470 msec for women and QTc>450 msec for men.

must be assigned as a biological male or female at birth, and identify as such

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