Neural Mechanisms of Disulfiram Effects
Condition: Alcohol Use Disorder
MeSH terms: Alcoholism; Alcohol Drinking
Intervention: Disulfiram
Intervention description: Patients will be hospitalized on an inpatient psychiatric unit for 1-7 days to initiate abstinence. An fMRI scan will be performed to examine neural mechanisms of alcohol motivation. Prior to discharge, patients will receive the first dose of disulfiram 500 mg. They will then attend an outpatient clinic every other day for 14 days. At each clinic visit, they will receive 500 mg of disulfiram under supervision. Another fMRI scan examining alcohol motivation will be performed. Following this, all patients will attend the clinic weekly, and will be prescribed disulfiram 250 mg daily to take at home. This will be followed followed by an optional extension of weekly visits taking disulfiram 250 mg daily for another 28 days, for a total of 70 days of disulfiram treatment.
Intervention MeSH terms: Disulfiram
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 21 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Alcohol; Craving; Functional MRI; Cognitive control; Risky decision-making; Disulfiram

Summary:

      This study combines functional MRI with medication treatment in order to understand the
      neural mechanisms by which disulfiram, a currently approved medication for alcohol use
      disorder, changes behavior. Disulfiram is a medication that prevents drinking by causing a
      highly unpleasant physical reaction when alcohol is consumed while it is being taken. Thus,
      it provides a means for studying the general neural mechanisms by which awareness of risks
      impacts behavior change in alcohol use disorder.
    

Eligibility criteria:

        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.