Design: This will be a randomized, double blind, 12-week clinical trial comparing the efficacy of intranasal self-administration of oxytocin (Syntocinon Spray \[intranasal oxytocin spray\], Novartis) vs. intranasal placebo (containing the same ingredients as Syntocinon Spray except for oxytocin) to in individuals with moderate Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) AUD and individuals with severe AUD who, in both groups, meet specific drinking criteria. Treatment assignments will be counterbalance within gender and within the moderate and severe AUD groups. The primary outcomes are measures of drinking: percentage of heavy drinking days (\>5 \[men\], \>4 \[women\] standard drinks), percentage of abstinent days, and mean standard drinks per drinking day based on Timeline Followback interview data collected at each clinic visit after randomization (1, 2, 3, 4, 6, 8, 10, and 12 weeks during the intranasal test treatment period; 6 and 12 weeks after cessation of test treatments). Secondary outcomes are subject self-ratings of craving for alcohol and anxiety on standardized questionnaires. Baseline measures of drinking, craving and anxiety will be covariates in statistical comparisons between the treatment groups of outcomes over the course of the treatment trial and the follow-up period.

Procedures Recruitment: Potential participants will be recruited from the Raleigh, Durham, and Chapel Hill, North Carolina areas by screening subjects who respond to community advertising. Respondents to advertisements will have a preliminary telephone screening conducted by the study coordinator. Individuals who appear eligible, as determined by the investigative team, will be scheduled for more comprehensive in-person screening.

Screening Clinic Visit: Prospective subjects who appear to meet study criteria based on phone interviews will come to the Psychiatry outpatient clinic at a scheduled time for in-person screening procedures to ascertain whether they truly meet study criteria (see Eligibility Criteria below). Initially individuals will read and sign the informed consent and be given a copy for their records. A breathalyzer test using an Alco-Sensor III breathalyzer machine (Intoximeters, Inc., St. Louis, MO) will be administered \[breath alcohol concentration (BrAC) must be 0.00 gms/dL to give informed consent\]. Medical personnel will administer the Clinical Institute Withdrawal Assessment of Alcohol (CIWA) Scale to determine if subjects are exhibiting significant alcohol withdrawal. The CIWA score must be \<6 for subjects to give informed consent. If the score is \>6, the visit will be rescheduled. In addition, blood pressure (BP) and heart rate (HR), height and weight will be measured and BMI calculated. Medical personnel will conduct a medical history and examination including a neurological examination. Over-the-counter and prescription medication use will be recorded. The Fagerstrom Test for Nicotine Dependence will be administered to smokers. Laboratory evaluations will include complete blood count (CBC) with differential; chemistries including bilirubin, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Gamma-glutamyl transferase (GGT), sodium, potassium, chloride, blood urea nitrogen, creatinine, and glucose; and urinalysis as well as urine toxicology (drug screen). A carbohydrate deficient transferrin (CDT) sample will be drawn. CDT samples will be stored frozen and then shipped in batches of 40 to Dr. Ray Anton's lab in Charleston, South Carolina for assay. CDT demonstrates excellent specificity to detect heavy alcohol use over time and has been shown to complement self-report measures of consumption. With subjects' permission, a sample of blood will also be obtained to archive for possible future genetic analyses. Women will be given a serum pregnancy test (β-HCG) at screening and a urine pregnancy test at wks 4, 8, and 12. Trained interviewers will conduct the psychiatric/substance disorder-screening interview using the Mini International Neuropsychiatric Interview. The Structured Clinical Interview for DSM-V Substance Use Disorders Module for AUD will be completed by a study physician to determine criteria for moderate or severe AUD. The study coordinator will conduct the pretreatment 90-day Timeline Followback interview (TLFB, Sobell et al, 1988) and potential participants will complete the entire Spielberger State Trait Anxiety Inventory (SSTAI), the Drinker's Inventory of Consequences, the Family History of Alcoholism Module (FHAM) to assess family history of alcohol problems, the University of Rhode Island Change Assessment Scale to assess motivation level, the Penn Alcohol Craving Scale to assess baseline craving, and the Insomnia Severity Index to assess baseline sleep problems. Additionally, potential participants will fill out a short evaluation of their treatment goals. This visit should take about 3 h.

Randomization Clinic Visit: Individuals meeting inclusion but not exclusion criteria will be informed and scheduled for the initial treatment visit within 10 days. Eligible individuals will not be required to abstain from drinking alcohol prior to randomization. The study coordinator will administer a breathalyzer test (BrAC must be ≤0.04 gm/dL; if \>0.04 gm/dL, the visit will be rescheduled), measure BP and HR, conduct the TLFB interview, and ask participants to complete the PACS, the state portion of the SSTAI (SSAI), and the Fagerstrom Test. After BrAC reading, but before the other procedures, the study physician will evaluate withdrawal symptoms using the CIWA and note the use of medications. If the CIWA score is \>6, the visit will be rescheduled. A 60 mL bottle containing 50 mL of test substance (oxytocin or placebo solution) with an intranasal spray mechanism that ejects 0.1 mL of aerosolized solution per insufflation as well as written instructions will be dispensed from the UNC Hospitals Investigational Drug Service according to the randomization schedule provide by Dr. Robert Gallop, Biostatistical Consultant on the project. The bottle will contain sufficient solution for the subject to self-administer intranasal test substance for at least 18 days so he/she will not run out if there is a delay in returning for the next clinic visit. Subjects will receive instructions for self-administration of intranasal test substance from members of the Study Team. Subjects will then self-administer their first dose of the intranasal substance to which they have been randomized \[ten insufflations delivering 40 IU of Syntocinon (oxytocin) Spray in a total of 1.0 mL of solution, or the same volume of placebo solution which contains all the ingredients in Syntocinon Spray except oxytocin\]. Subjects will pause 30 sec between insufflations and will alternate insufflations between nostrils. Study Team members will observe subjects' self-administration of their first dose to determine if their technique is correct and to correct any errors in technique. In our experience, subjects rapidly learn the self-administration technique. Participants also will be given a calendar style diary to record times of intranasal self-administration, drinking, and any side effects and a Self-Administration Instruction Sheet along with a wallet card informing providers that the subject may be taking oxytocin should the individual require emergency medical treatment. Finally, participants will receive Medical Management (MM) from a trained clinician (see details below). This visit should be completed in about 1.25-1.5 hours.

Subsequent Clinic Visits: Subjects will self-administer intranasal test doses BID (before breakfast and dinner) for 12 weeks. They will have outpatient clinic visits at weeks 1, 2, 3, 4, 6, 8, 10 and 12 after starting intranasal test treatments. The investigators will accept a window of ± 3 days for weekly visits and ± 7 days for biweekly visits in cases where a subject cannot come for the exact visit date. At each visit, the following will be obtained: breathalyzer (BrAC) reading; CIWA score; TLFB interview; BP; HR; the state portion of the SSTAI; and PACS. The DrInC will be completed again at week 12. BrAC readings must be \<0.04 and CIWA scores \<6 for assessments to be done at clinic visits (BrAC readings must be \<.08 to allow subjects to drive themselves home from any clinic visit). New spray bottles will be given every 2 weeks. The weight of bottles will be recorded when first issued and when returned during subsequent clinic visits. Change in weight will be our primary measure of compliance. Blood and urine samples will be obtained for CBC, electrolytes, Blood Urea Nitrogen (BUN), creatinine, liver function tests, urinalysis, urine drug screen and pregnancy tests at 4, 8, and 12 weeks. As during the randomization clinic visit, the psychosocial treatment provided during each subsequent clinic visit will be Medical Management (MM). At the 12-week clinic visit, subjects will be given information about a wide range of treatment options as well as contact information and will be offered assistance in making appointments.

Post-Treatment Follow-up: Subjects will return for follow-up clinic visits at 6 and 12 weeks (2 weeks also for follow-up measures if lab values at the 12-week clinic visit during the test treatment period are abnormal) after cessation of intranasal test treatments. Assessment at each follow-up visit will be BrAC, TLFB, PACS, SSAI, and questions about subjects' enrollment and attendance record in individual, group, and/or medication treatment.

Medical Management Intervention: The psychosocial treatment for the proposed study will be Medical Management (MM). Dr. Kampov will be primarily responsible for MM with Drs. Garbutt, Jordan and Pedersen providing additional coverage. Dr. Kampov and Dr. Garbutt have been trained and certified in MM by Dr. William Dundon of the University of Pennsylvania and along with Drs. Pedersen and Jordan have received MM training from Ms. Gail Kempf of the University of Pennsylvania. MM is designed as a means for physicians and other health care providers to encourage individuals with an AUD to make progress towards their drinking goals of reduction or abstinence and to encourage compliance with medication. Whereas the primary goal of MM is to encourage abstinence, the goal of reduction is acceptable and the investigators have used this "harm reduction" approach in our clinical trials to date. Many subjects have an initial goal of reduction that, over the course of trial participation, MM changes to abstinence. MM does not provide intense counseling methods for reducing drinking or dealing with relapse triggers and is thought to be an advantage for medication trials as MM does not overpower a possible medication effect. The average length of MM sessions is 10-15 minutes and an MM checklist is used in each session that greatly enhances consistency. The investigators will audio-record 10-20 MM sessions for review by MM providers to enhance fidelity.