Neural Mechanisms of Disulfiram Effects

Neurocognitive Mechanisms of Disulfiram Treatment of Alcohol Use Disorder

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.

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.