Neural Mechanisms of Disulfiram Effects

The overall goal of this project is to combine functional brain imaging and clinical methods
in order to examine how treatment with disulfiram (DIS) alters neural activity related to
alcohol-seeking motivation in patients with alcohol use disorder (AUD). DIS is an
established, effective, FDA-approved medication for AUD that causes a highly aversive
physical reaction if alcohol is consumed while it is being taken. The mere awareness of the
risk or threat the DIS-alcohol reaction deters alcohol use, i.e. it is not necessary to drink
alcohol while taking DIS to change behavior. By uncovering the neural mechanisms underlying
this risk/threat-based psychological effect, it will be possible to integrate DIS with
biologically based treatments targeted at these neural mechanisms, with the goal of improving
the efficacy of DIS. Furthermore, the results will shed light on the general neural
mechanisms by which awareness of risks of substance use impacts addictive motivation. This is
a core process in a number of behavioral treatments for substance use disorders, such as
Motivational Interviewing and Contingency Management, as well as in behavior change in
non-treatment settings.

Inclusion Criteria:

1. Between the ages of 21-60

2. Right-handed

3. Capable of giving informed consent and complying with study procedures

4. Reports drinking a minimum of 5 standard drinks for men or 4 standard drinks for women
on at least 4 days per week on average over the past 28 days

5. Meets DSM-V criteria for current Alcohol Use Disorder

6. Seeking treatment for Alcohol Use Disorder

7. Agree to not seek additional treatment, apart from Alcoholics Anonymous

8. Willing to attempt to abstain from alcohol completely for the duration of the study

9. Willing to be hospitalized on a research unit for 24 hours, longer if detoxification
is needed.

Exclusion Criteria:

1. Risk of severe alcohol withdrawal (e.g. history of seizures or delirium tremens)

2. Current Moderate or Severe Substance Use Disorder, other than Alcohol, Nicotine or
Caffeine Use Disorders

3. Lifetime history of Bipolar Disorder, Schizophrenia or Schizoaffective Disorder

4. Any current psychiatric disorder, other than Alcohol Use Disorder, that, in the
judgment of the investigator, will require treatment that will interfere with study
participation.

5. Current severe depression (HAM-D >24) or anxiety (HAM-A >24)

6. Significant suicide or violence risk

7. Currently taking any psychotropic medications

8. Legally mandated to participate in treatment

9. History of prior treatment with disulfiram

10. Sufficiently socially unstable as to preclude participation (e.g. homeless)

11. Contraindications to disulfiram treatment (liver disease, kidney disease, cardiac
disease, seizure disorder, hypothyroidism, diabetes mellitus, pregnancy or lactation,
allergy to disulfiram or thiuran derivatives)

12. Neurological or medical conditions that would interfere with MRI scanning (e.g.
history of stroke, seizure, brain tumor, brain infection, traumatic brain injury,
multiple sclerosis, dementia, metal device in body, pregnancy, claustrophobia, color
blindness, severe hearing impairment, weight>300 lbs., wheelchair-bound)

13. Currently taking medications containing alcohol, metronidazole, isoniazid,
paraldehyde, phenytoin, warfarin, or theophylline.

14. Significant alcohol withdrawal (CIWA>8) at screening, after confirming a blood alcohol
level of zero.