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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
180
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.
VA Connecticut Healthcare System
West Haven, Connecticut, United States
Number of Drinks Felt Consumed at Baseline
The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Time frame: Baseline
Number of Drinks Felt Consumed at 10 Minutes
The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Time frame: 10 minutes
Number of Drinks Felt Consumed at 30 Minutes
The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Time frame: 30 minutes
Number of Drinks Felt Consumed at 110 Minutes
The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Time frame: 110 minutes
Number of Drinks Felt Consumed at 140 Minutes
The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Time frame: 140 minutes
Number of Drinks Felt Consumed at 170 Minutes
The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Time frame: 170 minutes
Number of Drinks Felt Consumed at 230 Minutes
The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.
Time frame: 230 minutes
Visual Analog Scale of Similarity to Alcohol - Baseline
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Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Time frame: Baseline
Visual Analog Scale of Similarity to Alcohol -10 Minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Time frame: 10 minutes
Visual Analog Scale of Similarity to Alcohol - 30 Minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Time frame: 30 minutes
Visual Analog Scale of Similarity to Alcohol - 60 Minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Time frame: 60 minutes
Visual Analog Scale of Similarity to Alcohol - 110 Minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Time frame: 110 minutes
Visual Analog Scale of Similarity to Alcohol - 140 Minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Time frame: 140 minutes
Visual Analog Scale of Similarity to Alcohol - 170 Minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Time frame: 170 minutes
Visual Analog Scale of Similarity to Alcohol - 230 Minutes
Visual Analog Scale of Similarity to Alcohol data using the Likert scale (0 Not at all similar to alcohol - 7 Extremely similar to alcohol) evaluating the similarity of drug effects to alcohol
Time frame: 230 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative Baseline
Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Time frame: Baseline
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 10 Minutes
Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Time frame: 10 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 30 Minutes
Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Time frame: 30 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 60 Minutes
Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Time frame: 60 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 110 Minutes
Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Time frame: 110 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 140 Minutes
Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Time frame: 140 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 170 Minutes
Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Time frame: 170 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Sedative - 230 Minutes
Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)
Time frame: 230 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - Baseline
Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Time frame: Baseline
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 10 Minutes
Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Time frame: 10 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 30 Minutes
Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Time frame: 30 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 60 Minutes
Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Time frame: 60 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 110 Minutes
Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Time frame: 110 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 140 Minutes
Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Time frame: 140 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 170 Minutes
Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Time frame: 170 minutes
Biphasic Alcohol Effects Scale (BAES) - Subscale Stimulant - 240 Minutes
Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)
Time frame: 240 minutes
Visual Analog Scale (VAS) HIGH - Baseline
visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Time frame: Baseline
Visual Analog Scale (VAS) HIGH - 10 Minutes
visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Time frame: 10 minutes
Visual Analog Scale (VAS) HIGH - 30 Minutes
visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Time frame: 30 minutes
Visual Analog Scale (VAS) HIGH - 60 Minutes
visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Time frame: 60 minutes
Visual Analog Scale (VAS) HIGH - 110 Minutes
visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Time frame: 110 minutes
Visual Analog Scale (VAS) HIGH - 140 Minutes
visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Time frame: 140 minutes
Visual Analog Scale (VAS) HIGH - 170 Minutes
visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Time frame: 170 minutes
Visual Analog Scale (VAS) HIGH - 240 Minutes
visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)
Time frame: 240 minutes
Visual Analog Scale (VAS) Drowsy - Baseline
visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)
Time frame: Baseline
Visual Analog Scale (VAS) Drowsy - 10 Minutes
visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)
Time frame: 10 minutes
Visual Analog Scale (VAS) Drowsy - 30 Minutes
visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)
Time frame: 30 minutes
Visual Analog Scale (VAS) Drowsy - 60 Minutes
visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)
Time frame: 60 minutes
Visual Analog Scale (VAS) Drowsy - 110 Minutes
visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)
Time frame: 110 minutes
Visual Analog Scale (VAS) Drowsy - 140 Minutes
visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)
Time frame: 140 minutes
Visual Analog Scale (VAS) Drowsy - 170 Minutes
visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)
Time frame: 170 minutes
Visual Analog Scale (VAS) Drowsy - 230 Minutes
visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)
Time frame: 230 minutes
Hopkins Verbal Learning Task - Immediate Recall - Trial 1
Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 no words recalled - 12 all words recalled)
Time frame: 30 minutes - Trial 1
Hopkins Verbal Learning Task - Immediate Recall - Trial 2
Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 no words recalled - 12 all words recalled)
Time frame: 30 minutes - Trial 2
Hopkins Verbal Learning Task - Immediate Recall - Trial 3
Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 no words recalled - 12 all words recalled)
Time frame: 30 minutes - Trial 3
Hopkins Verbal Learning Task - Delay Recall
Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Delay Recall: 30 minutes after Trials 1-3 were given) (0 no words recalled - 12 all words recalled)
Time frame: 60 minutes
Pegboard Task - Baseline (Dominant Hand)
The pegboard task is a measure of coordination that measures reaction time; how long a subject takes to insert pegs into a pegboard puzzle, first using their dominant hand then using their non-dominant hand. A quicker time indicates greater coordination. Scores are timed in seconds
Time frame: Baseline
Pegboard Task - 30 Minutes (Dominant Hand)
The pegboard task is a measure of coordination that measures reaction time; how long a subject takes to insert pegs into a pegboard puzzle, first using their dominant hand then using their non-dominant hand. A quicker time indicates greater coordination. Scores are timed in seconds.
Time frame: 30 minutes
Pegboard Task - Baseline (Non-Dominant Hand)
The pegboard task is a measure of coordination that measures reaction time; how long a subject takes to insert pegs into a pegboard puzzle, first using their dominant hand then using their non-dominant hand. A quicker time indicates greater coordination. Scores are timed in seconds.
Time frame: Baseline
Pegboard Task - 30 Minuites (Non-Dominant Hand)
The pegboard task is a measure of coordination that measures reaction time; how long a subject takes to insert pegs into a pegboard puzzle, first using their dominant hand then using their non-dominant hand. A quicker time indicates greater coordination. Scores are timed in seconds.
Time frame: 30 minutes