Mechanistic Evaluation of Guanfacine on Drinking Behavior in Women and Men With Alcohol Use Disorders

Inclusion Criteria: 1. Age 21 70; 2. Able to read and write English; 3. Meets DSM V criteria for current (past 6 months) alcohol use disorder or Drinking criteria: Males Drinks more than 14 drinks per week and exceeds 4 drinks per day at least twice per week; Females Drinks \> more than 7 drinks per week and exceeds 3 drinks per day at least twice per week. Must meet drinking criteria during a consecutive 30 day period prior to baseline; 4. Laboratory sessions will be scheduled such that subjects will not have major responsibilities on the following day which might limit drinking during the self administration session (e.g., job interview, exam); 5. Able to take oral medications and willing to adhere to medication regimen; 6. indicate willingness to cut down on drinking during the treatment period. Exclusion Criteria: 1. Subjects with any significant current medical conditions (neurological, cardiovascular \[including hypertension or hypotension: sitting BP more than 160/100 or less than 90/60mmHg at baseline screening\], endocrine, thyroid, renal, liver), seizures, delirium or hallucinations, or other unstable medical conditions including HIV; 2. Current DSM V substance use disorder, other than alcohol abuse disorder or nicotine dependence; 3. A positive test result at intake appointment on urine drug screens conducted for illicit drugs; 4. Past 30 day use of psychoactive drugs including anxiolytics and antidepressants; 5. Women who are pregnant or nursing, or fail to use one of the following methods of birth control unless she or partner is surgically sterile or she is postmenopausal (hormone contraceptives \[oral, implant, injection, patch, or ring\], contraceptive sponge, double barrier \[diaphragm or condom plus spermicide\], or IUD); 6. Suicidal, homicidal or evidence of current (past 6 month) mental illness such as schizophrenia, bipolar disorder or major depression, or anxiety disorders; 7. Meet DSM V criteria for current (past 6 month) ADHD; 8. Only one member per household can participate in the study 9. Specific exclusions for administration of guanfacine not already specified include: EKG evidence at baseline screening of any clinically significant conduction abnormalities or arrhythmias; known intolerance for guanfacine or any alpha blocker; history of fainting, syncopal attacks, heart failure or myocardial infarction, or impaired liver (AST, ALT \> 3x normal) or renal function (estimated creatinine clearance \<60 cc/min); treatment with any antihypertensive drug or any alpha adrenergic blocker; use of any CNS depressant (e.g., phenothiazines, barbiturates, benzodiazepines); 10. Subjects likely to exhibit clinically significant alcohol withdrawal during the study. Specifically, we will exclude subjects who a) have a history of perceptual distortions, seizures, delirium, or hallucinations upon withdrawal, or b) have a score of more than 8 on the Clinical Institute Withdrawal Assessment scale at intake appointments; 11. Subjects who have taken any investigational drug within 4 weeks immediately preceding admission to the treatment period; 12. Participation within the past 8 weeks in other studies that involve additive blood sampling and/or interventional measures that would be considered excessive in combination with the current application; 13. at intake express desire to completely abstain from alcohol; 14. currently in treatment for alcohol use