Carisbamate as a Potential Treatment for Alcohol Dependence

This within-subjects placebo-controlled experimental protocol will assess the effects of
carisbamate (600mg qd) on the positive subjective effects of alcohol in non-treatment-seeking
alcohol-dependent volunteers. Participants will receive study drug (carisbamate or placebo)
from days 2- 4. On day 4, study drug will be followed by alcohol (0.8g/kg; 16% by volume) and
a placebo beverage (1% by volume as a mask), both separated by 2 hours. Physiologic,
subjective effects and BAL will be obtained after the alcohol challenges. Participants will
be discharged on day 4 and asked to return a week later to repeat the study under the
alternate study drug condition (active carisbamate vs. placebo).

Inclusion Criteria:

1. Be an English-speaking volunteer who is not seeking treatment at the time of the study

2. Be between 18-55 years of age

3. Meet DSM-IV TR criteria for alcohol abuse; participants may or may not meet criteria
for nicotine dependence. Nicotine dependence is allowed but not required because most
alcohol users smoke cigarettes.

4. Have a self-reported history of using alcohol.

5. Have vital signs as follows: resting pulse must be < 90 bpm and the blood pressure
must be < 150 mmHg systolic and < 90 mmHg diastolic.

6. Have hematology and chemistry laboratory tests that are within normal (+/- 10%) limits
with the following exceptions:

- liver function tests (total bilirubin, ALT, AST, and alkaline phosphatase) < 3 x
the upper limit of normal, and b) kidney function tests (creatinine and BUN)
within normal limits

7. Have a baseline EKG that demonstrates clinically normal sinus rhythm, clinically
normal conduction, and no clinically significant arrhythmias

8. Have a medical history and brief physical examination demonstrating no clinically
significant contraindications for study participation, in the judgment of the
admitting physician and the principal investigator.

Exclusion Criteria:

1. Meet DSM IV TR criteria for dependence on drugs other than alcohol or nicotine.

2. Have any history or evidence suggestive of seizure disorder or brain injury

3. Have any previous medically adverse reaction to alcohol, including loss of
consciousness, chest pain, or epileptic seizure

4. Have neurological or psychiatric disorders, such as:

- psychosis, bipolar illness or major depression as assessed by SCID

- organic brain disease or dementia assessed by clinical interview

- history of any psychiatric disorder which would require ongoing treatment or
which would make study compliance difficult

- history of suicide attempts within the past year and/or current suicidal
ideation/plan

5. Have evidence of clinically significant heart disease or hypertension, as determined
by the PI

6. Have evidence of untreated or unstable medical illness including: neuroendocrine,
autoimmune, renal, hepatic, or active infectious disease

7. Have symptomatic HIV or are taking antiretroviral medication

8. Be pregnant or nursing. Other females must either be unable to conceive (i.e.,
surgically sterilized, sterile, or post-menopausal) or be using a reliable form of
contraception (e.g., abstinence, birth control pills, intrauterine device, condoms, or
spermicide). All females must provide negative pregnancy urine tests before study
entry, upon hospital admission, and at the end of study participation

9. Have any other illness, condition, or use of psychotropic medications, which in the
opinion of the PI and/or the admitting physician would preclude safe and/or successful
completion of the study.

10. Currently seeking help for alcohol dependence.

11. Subjects with or prone to clinically significant alcohol withdrawal.

12. More than thirty days of abstinence from alcohol in the ninety days prior to
enrollment.

13. A history of major alcohol-related medical complications requiring hospitalization
(i.e. pancreatitis).

14. Contraindication(s) to take the study medication such as renal or hepatic impairment,
nephrolithiasis, congenital metabolic disorders or history of seizures.
Moderate-to-severe renal impairment defined as creatinine clearance less than 30
mL/min.

15. Use of inhibitors/substrates for renal cationic transporters, or medications
contraindicated with ethanol.

16. A history of violence or aggression, assessed as part of the clinical interview at
screening visit.