Alkontrol-herbal Effects on Alcohol Drinking

Over the past 15 years, the Behavioral Psychopharmacology Research Lab at McLean Hospital has
extensively studied kudzu extract and demonstrated its safety and efficacy in healthy control
subjects as well as in heavy binge drinkers. The relative success of our recent outpatient
trial of kudzu extract demonstrated a modest decrease in drinking, reduction in the number of
heavy drinking days, and significant increase in the number of days abstinent. This suggests
that Alkontrol-herbal, kudzu extract, may be a useful adjunct in treating alcohol use
disorders.

Participants will enroll in a 14-week study (2 weeks of baseline, 8 weeks of treatment, and 4
weeks of follow-up) investigating the impact that Alkontrol-herbal has on alcohol intake in a
population (age 21-60 years) seeking treatment for an alcohol use disorder. Participants will
take 500 mg of a crude kudzu extract (NPI-031, Alkontrol-herbal; Natural Pharmacia
International, Burlington, MA) t.i.d.; matched sugar beet placebo capsules will serve as
placebo. Subjects will come to the lab three times a week to provide urine samples that can
be tested for medication compliance through a biochemical marker, acetazolamide, included in
the medication capsules. Participants will record their alcohol intake through daily diaries
and a wrist actigraphy device, which will also monitor their sleep/wake activity.

Inclusion Criteria:

- Subject can understand and comply with the protocol

- Good physical and mental health (normal physical exam, ECG, blood and urine
chemistries, including absence of history or laboratory evidence of diabetes)

- Body Mass Index between 18-30, inclusive

- Age 21-60 years (age will be verified by driver's license or other valid form of
identification)

- Meet criteria for current Moderate or Severe (4+ symptoms) Alcohol Use Disorder per
the DSM-5; If attending a self-help treatment group (e.g., AA) at time of the
screening visit, subject must agree to continue attending these groups for the
duration of the study

- Seeking treatment for an Alcohol Use Disorder

- Drink 20-35 (or more) drink per week

- Report drinking on 80% of days in the past 90 days

- Have a stable living situation with current postal address

Exclusion Criteria:

- Subject meets DSM-5 criteria for major depression and/or bipolar disorder, and is not
medically, pharmacologically, or clinically stable. Subjects who currently meet
criteria for minor depression or bipolar disorder and have been clinically stable
(including medications) for the past 2 months may participate in the study, at the
investigator's discretion

- Concurrent diagnosis of any other Axis I disorder, including any substance use
disorder besides alcohol use disorder Maintained on an antipsychotic or anti-seizure
medication; Current prescription for benzodiazepines

- Presence of neurological, infectious, or neoplastic disease or a chronic medical
disorder

- Tobacco use greater than 10 cigarettes per day

- Currently abstaining from consuming alcoholic beverages longer than 10 days

- History of major head trauma resulting in cognitive impairment or history of seizure
disorder

- Heavy caffeine use (greater than 500 mg on a regular, daily basis)

- Subject has active hepatitis and/or aspartate aminotransferase (AST), alanine
aminotransferase (ALT) > 3x the upper limit of normal

- For female volunteers, a positive pregnancy test (female subjects must agree to an
approved method of contraception for the duration of the study)