This is a Phase 2 single site randomized clinical trial (RCT) to be supported by a new NIH-NIAAA grant, R01-AA029113-01, to assess the efficacy of Prazosin (16mg/day) versus Placebo over a 12 week treatment period, followed by a 1- and 3- month assessments post-treatment for individuals with Alcohol Use Disorder (AUD) and history of past or current evidence of alcohol withdrawal symptoms. If medical detoxification is required for any patient, patients would be enrolled after medical detoxification. for those not requiring detoxification, they will be enrolled directly without any requirement of alcohol abstinence. All patients will be provided behavioral counseling weekly with a trained counselor to support recovery during the trial. Primary outcome will be percent of any heavy drinking days and secondary drinking outcomes will be percent of subjects with no heavy drinking days (PSNHDD), avg drinks per drinking day and %of any drinking drinking days as well as additional secondary outcomes of craving, mood and anxiety problems.

In this Phase 2 single site RCT, individuals with moderate to severe alcohol use disorder (AUD) and presence of alcohol withdrawal symptoms (greater than 3 symptoms or more) will be enrolled in a 12 week trial with a 1- and 3- month follow up assessment. Subjects will be randomized to 16 mg /day Prazosin (PR) or Placebo (PBO) with a 2 week titration period and9-week full dose period and week 12 taper. All subjects will be assessed 2X weekly and also provided weekly behavioral counseling to support recovery.

Inclusion Criteria:

• Alcohol Withdrawal (AW) scores of 3 or more on the CIWA-Ar at treatment entry OR 2 or more Alcohol Withdrawal Syndrome (AWS) symptoms and regular weekly heavy drinking at treatment entry;
• Must meet current DSM-5 criteria for moderate to severe Alcohol Use Disorder (AUD) using SCID-I for DSM-5;
• No health conditions that would impact trial participation as verified by screening and physical examination;
• Able to read English and complete study evaluations
• Able to provide informed written and verbal consent.

Exclusion Criteria:

• Meet current criteria for moderate to severe substance use disorders from use of any another psychoactive substance, excluding nicotine, cocaine and cannabis;
• Current use of illicit /non-prescribed opioids more than 2X/month;
• Regular use of anticonvulsants, sedatives/hypnotics, oral prescription analgesics (other than non-steroidal anti-inflammatory drugs), antiretroviral medications, tricyclic antidepressants, topiramate, baclofen, and regular weekly use of benzodiazepines, as defined by use of three or more times per week;
• Prescribed use of antihypertensive medications that duplicate the mechanism of action at the alpha1 receptor as prazosin or are contraindicated, such as those medications that are also alpha1-adrenergic antagonists (i.e., doxazosin, tamsulosin, terazosin) or are beta-blockers (e.g., propranolol); Potential participants who are prescribed cardiovascular/antihypertensive medications will undergo clinical review by the study PIs and team. Individuals who are prescribed anti-hypertensives that do not duplicate the action of prazosin and are not contraindicated, including ACE inhibitors, angiotensin receptor blockers (ARBs), diuretics, and calcium channel blockers, may be allowed to participate after review from the study physician and principal investigators, with careful monitoring of these individuals' blood pressure at all in-person appointments.
• Psychotic or otherwise severely psychiatrically disabled (i.e., suicidal, homicidal, current mania);
• Significant underlying medical conditions such as cerebral, renal, thyroid or cardiac pathology which in the opinion of study physician would preclude patient from fully cooperating or be of potential harm during the course of the study;
• Any psychotic disorder or current Axis I psychiatric disorders requiring specific attention, including need for psychiatric medications;
• Hypotensive individuals with sitting blood pressure below 100/50 mmHG;
• Women who are pregnant, nursing or refuse to use a reliable form of birth control (as assessed by pregnancy tests during initial medical evaluation, and assessed every two weeks during the course of the study).

De-identified data will be uploaded to NIAAA data archive (NIAAA-DA housed within the NIMH Data archive (NDa). as per NIH-NIAAA guidelines.

Baseline data will be uploaded twice yearly. clinical trial outcome data will be shared after study completion and breaking the blind and completion of final analysis of the main study outcomes.

Access will be provided following the NIH-NIAAA guidelines available at https://grants.nih.gov/grants/guide/notice-files/NOT-AA-19-020.html at the URL below.