Intravenous Alcohol Administration Using BrAc Method in Healthy Subjects With and Without a Family History of Alcoholism
Condition: Alcoholism
MeSH terms: Alcoholism
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Ethanol High Dose, Ethanol Low Dose, and Placebo
Intervention type(s): Drug
Intervention description(s): Three test days will involve administration of placebo, ethanol high dose (BrAc=100mg%) or ethanol low dose (BrAc=40mg%)intravenously for approximately 20 minutes, until the target BrAc is achieved. Once BrAc is achieved (40mg% or 100mg%) it will be maintained using a clamp procedure for 60 minutes.
Other intervention name(s): intravenous
Intervention MeSH terms: Ethanol
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Other