Rapid Determination Of The Clinical Utility Of Perampanel For The Treatment Of Alcohol Dependence

The main goal of the proposed study is to determine whether the AMPA-R antagonist perampanel
alters the response to ethanol (i.e., the rewarding and reinforcing effects) using a
validated laboratory paradigm of intravenous (IV) ethanol infusion. Fifty non-treatment
seeking heavy drinkers (NTSHDs, N=50), will undergo three test days each: once after
receiving a placebo medication, once after receiving moderate dose perampanel, and once
after receiving a higher dose of perampanel. This experiment is the first step in a series
of expedient studies that will rapidly determine perampanel's potential as a treatment for
alcohol dependence. If findings show perampanel reduces the rewarding and reinforcing
properties of alcohol in the laboratory setting (in humans), it would provide a strong
rationale for clinical treatment trials with this medication. This approach is innovative
because it tests a highly novel AMPA-R antagonist for the treatment of alcoholism, and uses
a state-of-the-art computer assisted IV alcohol pump infusion system (called CAIS) to reduce
variability in blood alcohol concentrations, thus improving the data quality.

Inclusion Criteria:

- males and females

- between the ages of 21 and 55 years;

- NTSHDs as defined above, and must have had at least 5 SD in one day on at least some
occasions in the past and been able to tolerate it without an adverse reaction

- generally medically and neurologically healthy on the basis of history, physical
examination, EKG, screening laboratory results (CBC w/ differential, TSH, Free-T4,
AST, ALT, GGT, BUN, creatinine, electrolytes, urinalysis, beta-HCG). Individuals with
LFTs that are no more than 3 times above the normal levels will be included;

- women with a negative pregnancy test and not nursing, must be regularly using birth
control

- negative breath alcohol at screening and on each test day;

- not taking any psychoactive medication or opioids (in past 30-days);

- are non-treatment seeking.

Exclusion Criteria:

- they need detoxification determined by a CIWA score of >8 or have had a history of
alcohol detoxification in the past;

- have been in treatment for an alcohol problem within the last 6 months, or if the
severity of their alcohol problem based on the research physician's assessment
warrants definitive treatment;

- meet criteria for DSM-IV psychiatric and substance use disorder diagnosis (other than
alcohol abuse/dependence, and nicotine dependence; those diagnoses will be allowed;
participants can be either smokers up to 1 pack per day or non-smokers) based on
history and psychiatric evaluation that includes a structured diagnostic interview
(Structured Clinical Interview for DSM-IV Axis I Disorders: SCID)

- unwillingness to remain alcohol-free 12 hours prior to test days;

- have a significant ongoing serious medical condition such as Diabetes Mellitus, liver
disease (see above LFT guideline), renal disease (as evidenced by serum creatinine
above our laboratory's reference limit of 1.7 mg/dL, or have a history of adverse
reaction to IV placement/blood draw