Oxytocin and Stress Response in Alcohol Use Disorder

Participants: Twenty-four individuals with AUD will be recruited through the Clinical Intake
and Assessment (CIA) Core of the Alcohol Research Center (ARC). Screening and basic
assessments will be conducted by the CIA Core to determine eligibility and suitability for
participation in this pilot project. Each individual will sign an Institutional Review Board
(IRB)-approved informed consent form.

Study Visit Assessments: The Drinking Motives Questionnaire Revised will be used to assess
motivation for drinking across four subscales: (1) coping motives; (2) social motives; (3)
conformity motives; and (4) enhancement motives. The Form 90 will be used to assess daily
alcohol consumption in the 90 days prior to the study visit and the time from last drink . A
modification of the Within Session Rating Scale will be used to assess craving and mood.

Study Visit Procedures: Participants will be asked to arrive at the Addiction Sciences
Division on the study visit day. Female participants will have their urine tested for
pregnancy. Females who test positive for pregnancy will be excluded. All participants will be
tested for drugs of abuse and alcohol. Patients testing positive for drugs, with the
exception of marijuana, will be excluded; patients testing positive for alcohol may be
re-scheduled. Participants will be asked about substance use in the last 90 days and will
fill out the Drinking Motives Questionnaire. Subjects who have not had a research physical
exam within the last 30 days will have a physical completed. They will then be escorted to
the scanner at 30 Bee Street.

The study will use a double-blind placebo controlled design. Intranasal OT (n=12) or PBO
(n=12) sprays will be administered at 11:30 am, approximately 45 min prior to the scanning
session. This dose and timing of OT administration were selected based on the literature.

MIST Procedure: The study will use a block design of three, 6-min runs separated by 2-min of
rest for feedback, for a total of 24 min. During each run, participants will be exposed to
40-sec blocks of three different conditions (rest, control, and experimental). Prior to the
task, participants will are shown images of what the screen will look like during each
condition. The participants will be instructed to relax during the rest condition and focus
on the screen. During the control condition, the participants will be asked to answer math
problems as accurately as possible but will also be told that their responses will not be
recorded. During the experimental condition, the participants will be asked to perform the
math task as quickly and accurately as possible. A performance bar located on the screen will
allow them to see their performance as compared to an "average" person. The participants will
be told that the average person would answer about 85% of the problems correctly; however,
the program limits the participants' performance rate to between 35-45%. A time limit will be
enforced throughout the experimental condition. After each run, the participants will be
given negative feedback from the investigator.

Blood Oxygen Level Dependent (BOLD)-fMRI Procedure: Data will be acquired on a Siemens Trio
3T scanner in MUSC's Center for Biomedical Imaging. For co-registration and normalization of
functional images, a high resolution T1-weighted Magnetization-Prepared Rapid Acquisition
with Gradient Echo (MPRAGE) anatomical image will be acquired with the following parameters:
Time of Repetition (TR)= 2100 ms, Echo Time (TE)= 4.18 ms, flip angle= 12°, field of view=
256 mm, slice thickness= 1.0 mm. The scanning planes will be oriented parallel to the
anterior commissure-posterior commissure line. Participants will be asked to relax and keep
their eyes opened and fixed on a cross-hair for 6 min while resting state data are collected.
Participants will then complete the MIST. T2*-weighted gradient-echo planar images (EPI) will
be acquired with the following parameters: TR= 2000 ms, TE= 27 ms, flip angle= 76º, matrix 64
x 64, field of view= 23 cm, slice thickness= 3.7 mm with no gap, with 36 slices to cover the
entire brain.

Inclusion Criteria:

1. Age 21-40.

2. Subjects must be able to provide informed consent and function at an intellectual
level sufficient to allow accurate completion of all assessment instruments.

3. Meets the DSM 5 criteria for current alcohol use disorder.

4. Reports drinking on average, at least 20 standard alcoholic drinks per week for at
least the past three months.

5. Currently not engaged in, and does not want treatment for, alcohol related problems.

6. Lives within 50 miles of the study site.

7. Subjects must consent to random assignment.

8. Able to maintain abstinence for two days (without the aid of detoxification
medications) as determined by self report and breathalyzer measurements Subjects must
also have a negative breathalyzer urine drug screen at the study visit.

9. Subjects must consent to the study visit which includes an outpatient admission to the
Addiction Sciences Division and completing one functional magnetic resonance imaging
(fMRI) scanning session.

Exclusion Criteria:

1. Currently meets DSM 5 criteria for any other psychoactive substance use disorder.

2. Is determined

3. Any psychoactive substance use (except marijuana and nicotine) within the last 30 days
by self-report and urine drug screen. For marijuana, no use within the last seven days
by verbal report and negative (or decreasing) urine THC levels.

4. Meets DSM 5 criteria for current major depression, panic disorder,
obsessive-compulsive disorder, post traumatic stress syndrome, bipolar affective
disorder, schizophrenia, dissociate disorders, eating disorders, and any other
psychotic disorder or organic mental disorder.

5. Has current suicidal ideation or homicidal ideation.

6. Has the need for maintenance or acute treatment with any psychoactive medication
including anti-seizure medications and medications for ADHD.

7. Is currently taking medication known to affect alcohol intake (e.g., disulfiram,
naltrexone, acamprosate, topiramate).

8. Has clinically significant medical problems such as cardiovascular, renal, GI,
neurological (e.g. seizure disorder) or endocrine problems that would impair
participation or limit medication ingestion.

9. Has past history of alcohol related medical illness such as gastrointestinal bleeding,
pancreatitis, peptic ulcer, hepatic cirrhosis or alcoholic hepatitis.

10. Has hepatocellular disease indicated by elevations of SGPT (ALT) or SGOT (AST) greater
than 2.5 times normal at screening.

11. Females of childbearing potential who are pregnant (by urine HCG), nursing, or who are
not using a reliable form of birth control.

12. Has current charges pending for a violent crime (not including DUI related offenses).

13. Does not have a stable living situation.

14. Presence of ferrous metal in the body, as evidence by metal screening and self-report.

15. Severe claustrophobia or morbid obesity that preclude placement in the MRI scanner.

16. History of head injury with >2 minutes of unconsciousness.