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 Drinkingcriteria: Males Drinks more than 14 drinks per week and exceeds 4 drinks per day atleast twice per week; Females Drinks > more than 7 drinks per week and exceeds 3drinks per day at least twice per week. Must meet drinking criteria during aconsecutive 30 day period prior to baseline;

4. Laboratory sessions will be scheduled such that subjects will not have majorresponsibilities on the following day which might limit drinking during the selfadministration 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 160/100or less than 90/60mmHg at baseline screening], endocrine, thyroid, renal, liver),seizures, delirium or hallucinations, or other unstable medical conditions includingHIV;

2. Current DSM V substance use disorder, other than alcohol abuse disorder or nicotinedependence;

3. A positive test result at intake appointment on urine drug screens conducted forillicit 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 ofbirth control unless she or partner is surgically sterile or she is postmenopausal (hormone contraceptives [oral, implant, injection, patch, or ring], contraceptivesponge, double barrier [diaphragm or condom plus spermicide], or IUD);

6. Suicidal, homicidal or evidence of current (past 6 month) mental illness such asschizophrenia, 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 conductionabnormalities or arrhythmias; known intolerance for guanfacine or any alpha blocker;history of fainting, syncopal attacks, heart failure or myocardial infarction, orimpaired liver (AST, ALT > 3x normal) or renal function (estimated creatinineclearance <60 cc/min); treatment with any antihypertensive drug or any alphaadrenergic blocker; use of any CNS depressant (e.g., phenothiazines, barbiturates,benzodiazepines);

10. Subjects likely to exhibit clinically significant alcohol withdrawal during thestudy. Specifically, we will exclude subjects who a) have a history of perceptualdistortions, seizures, delirium, or hallucinations upon withdrawal, or b) have ascore of more than 8 on the Clinical Institute Withdrawal Assessment scale at intakeappointments;

11. Subjects who have taken any investigational drug within 4 weeks immediatelypreceding admission to the treatment period;

12. Participation within the past 8 weeks in other studies that involve additive bloodsampling and/or interventional measures that would be considered excessive incombination with the current application;

13. at intake express desire to completely abstain from alcohol;

14. currently in treatment for alcohol use