Conditions: Alcoholism
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 180
Healthy volunteers: yes

Brief 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.

Arms:
arm 1: Subjects with a positive family history of alcoholism. arm 2: Subjects with a negative family history of alcoholism.

Interventions: intervention 1: Ethanol High Dose, Ethanol Low Dose, and Placebo
Intervention descriptions: intervention 1: 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.

Protocol document: