Intravenous Alcohol Administration Using BrAc Method in Healthy Subjects With and Without a Family History of Alcoholism
Intravenous Alcohol Administration Using BrAc Method in Healthy Subjects With and Without a Family History of Alcoholism
The proposed study is the first to explore the contribution of brain glutamate systems, a
 major target of ethanol in the brain, to the vulnerability to develop alcoholism. This study
 may lead to an enhanced understanding of the underlying neurobiological mechanism in high
 risk individuals that may lead to the transition from moderate to excessive use of alcohol.
Males and females with a paternal family history of alcoholism have a high risk for
 developing alcoholism. These individuals have been shown to have decreased dysphoric
 responses to alcohol self-administration that may promote the excessive use of alcohol.
 Ethanol has been shown to be an antagonist at the N-methyl-D-aspartate (NMDA) glutamate
 receptor. We have recently shown that sober alcoholics have decreased dysphoric response to
 the NMDA antagonist, ketamine. We propose to test the hypothesis that this characteristic
 exists as a vulnerability factor in those individuals susceptible to develop alcoholism.
 Specifically, the objective is to determine whether individuals with a family history
 positive (FHP) for alcoholism will experience less dysphoric, anxiogenic, and psychotogenic
 effects to alcohol infusion when compared to family history negative (FHN) control subjects.

 Male and female subjects, FHP (biological father and one other first degree relative) between
 the ages of 21-30, and matched controls (FHN) will complete 3 test days in a randomized
 balanced order under double-blind conditions. Test days will involve administration of
 placebo or one of two ethanol doses (target BrAc=40mg%, or target BrAc=100mg%) intravenously
 for 20 minutes, until the target BrAc is achieved. Once BrAc is achieved (40mg% or 100mg%) it
 will be maintained using a clamp procedure for over 60 minutes. Outcome measures include the
 Positive and Negative Symptom Scale, visual analog scales of mood state, (i.e. anxiety) and
 the Clinician-Administered Dissociative States Scale (CADSS) to measure perceptual responses
 to alcohol. Secondary measures include visual analog scales for high, similarity to ethanol,
 Mini Mental Status Examination (MMSE), Placement of electrodes, Biphasic Alcohol Effects
 Scale, Hopkins Verbal Learning, and number of drinks scale, aspects of craving for alcohol
 and tests of cognitive impairment.
Inclusion Criteria:

 1. Male and female between the ages of 21 and 30 years;

 2. medically and neurologically healthy on the basis of history, physical examination,
 EKG, Screening laboratories absence of current and/or past substance abuse on the
 basis of history and urine toxicology and breath alcohol levels at screening and on
 each test day.

 For Family History Positive (FHP) Subjects: 1) Biological father and another first or
 second-degree biological relative with history of alcoholism by Family History Assessment
 Module (FHAM) developed by COGA.

 Exclusion Criteria:

 1. DSM-IV psychiatric and substance abuse (excluding alcohol abuse) diagnosis by history
 on psychiatric evaluation that includes a structured diagnostic interview (Structured
 Clinical Interview for Diagnostic and Statistical Manual (DSM)-IV Axis I Disorders
 (SCID))

 2. Subjects who meet criteria for alcohol abuse and express an interest in stopping
 alcohol use and/or express an interest in treatment or are currently enrolled in
 treatment for alcoholism, or have sought treatment in the last 6 months.

 3. history of counseling or psychotherapy; except family therapy centered around another
 family member

 4. extended unwillingness to remain alcohol-free for 48 hours prior to test days;

 5. for women: positive pregnancy test at screening or intention to engage in unprotected
 sex during the study

 6. alcohol naïve

 7. Adoptee and no contact with family members.