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

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.

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.

The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

The Number of Drinks Scale asks Subjects to report on the number of alcoholic drinks they felt they had consumed.

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

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

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

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

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

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

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

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

Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

Self-report rating scale used to measure sedative effects (0 not at all sedated - 70 extremely sedated)

Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

Self-report rating scale used to measure stimulant effects (0 not at all stimulated - 70 extremely stimulated)

visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

visual analog scale (VAS): self-report scale used to measure high (0 not at all High - 7 extremely High)

visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)

visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)

visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)

visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)

visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)

visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)

visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)

visual analog scale (VAS): self-report scale used to measure Drowsy (0 not at all drowsy - 7 extremely drowsy)

Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 no words recalled - 12 all words recalled)

Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 no words recalled - 12 all words recalled)

Hopkins Verbal Learning Task (HVLT) - measures verbal memory and hippocampus function. (Three immediate recall trials) (0 no words recalled - 12 all words recalled)

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)

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

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.

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.

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.

Inclusion Criteria: Male and female between the ages of 21 and 30 years; 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: 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)) 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. history of counseling or psychotherapy; except family therapy centered around another family member extended unwillingness to remain alcohol-free for 48 hours prior to test days; for women: positive pregnancy test at screening or intention to engage in unprotected sex during the study alcohol naïve Adoptee and no contact with family members.

Ralevski E, Perrino A, Acampora G, Koretski J, Limoncelli D, Petrakis I. Analgesic effects of ethanol are influenced by family history of alcoholism and neuroticism. Alcohol Clin Exp Res. 2010 Aug;34(8):1433-41. doi: 10.1111/j.1530-0277.2010.01228.x. Epub 2010 May 21.

Perrino AC Jr, Ralevski E, Acampora G, Edgecombe J, Limoncelli D, Petrakis IL. Ethanol and pain sensitivity: effects in healthy subjects using an acute pain paradigm. Alcohol Clin Exp Res. 2008 Jun;32(6):952-8. doi: 10.1111/j.1530-0277.2008.00653.x. Epub 2008 Apr 26.