Medication Development for Opioid and Alcohol Abuse

Currently, the abuse of prescription opioid medications is a pervasive problem in the U.S. In
addition, co-abuse of opioids and alcohol represents a significant problem from the
perspective of increased toxicity and decreased success in treatment. Surprisingly few
studies have examined the effects of combined administration of opioids and alcohol in
humans, and no clinical studies have examined the reinforcing effects of this combination.
The current 8-9-week inpatient study will systematically evaluate gabapentin because it shows
promise for treating both opioid and alcohol use disorders (OUD and AUD). The guiding
principle is that a medication's effects on positive subjective responses and reinforcing
effects are the best laboratory procedures to date in predicting its clinical efficacy. We
will examine the ability of gabapentin to alter opioid-, alcohol-,and combined
opioid/alcohol-mediated responses. Participants will meet DSM-5 criteria for moderate-severe
OUD and be physically dependent on opioids. In addition, participants will meet DSM-5
criteria for moderate-severe AUD, but they will not be physically dependent on alcohol. All
of the participants will be maintained on oral morphine throughout the study and different
doses of gabapentin will be evaluated.

Inclusion Criteria:

1. DSM-5 criteria for moderate-severe opioid use disorder with physical dependence.

2. DSM-5 criteria for moderate-severe alcohol use disorder without physical dependence.

3. No current major mood, psychotic, or anxiety disorder.

4. Physically healthy.

5. Able to perform study procedures.

6. 21-59 years of age.

7. Normal body weight/Within 20% of body weight (for appropriate frame) according to 1983
Metropolitan Weight tables.

8. Current or history of illicit opioid use.

9. Current use of opioids in amounts and/or frequencies that meet or exceed those used in
the proposed study (e.g., 3-4 tablets of a Rx opioid medication per day or 1-2 bags of
heroin per day). Not seeking treatment for opioid use disorder (neutral attitude or
not wanting treatment only).

10. Participants will consume alcohol at least 3 times per week (15 drinks per week for
men and 8 drinks per week for women). In addition, they will drink alcohol and use
opioids simultaneously.

Exclusion Criteria:

1. DSM-5 criteria for substance use disorder (moderate to severe) on drugs other than
opioids, alcohol, nicotine or caffeine (must be less than 500 mg caffeine daily).

2. Participants requesting treatment.

3. Pregnancy or lactation.

4. Current or recent history of significant violent or suicidal behavior and/or
suicidal/homicidal risk.

5. Cannot read or understand the self-report assessment forms unaided, or are so severely
disabled that they cannot comply with the requirements of the study.

6. Elevated liver function tests (i.e., AST and ALT > 3 times the upper limit of normal)
or impaired renal function (creatinine must be within normal limits).

7. Physical disorders that might make participation hazardous such as AIDS, cancer,
hypertension (blood pressure > 140/90), uncontrolled diabetes, pulmonary hypertension
or heart disease (please note that participants will be asked about previous visits to
a cardiologist, chest pain, or strong palpitations; if these exist, they will be
referred to a cardiologist and excluded unless cleared for participation by a
cardiologist).

8. Current major Axis I psychopathology, other than OUD and AUD (e.g., mood disorder with
functional impairment, schizophrenia), that might interfere with ability to
participate in the study.

9. Sensitivity, allergy, or contraindication to opioids, alcohol, gabapentin or similar
medications.

10. Taken an investigational drug within the past 30 days.

11. Current or history of chronic pain within the past 3 months.

12. Taking prescription psychotropic medications that would potentially interfere with
study procedures.