Healthy Volunteers Clinical Trial
Official title:
Measuring Effects of Acute Ethanol on Human Brain Metabolites Using Magnetic Resonance Spectroscopy
Background:
- Studies show that alcohol changes the amount of many brain chemicals. These changes may be
related to continued drinking, craving for alcohol, and relapse. This study will use magnetic
resonance imaging (MRI) to look at brain areas and brain chemistry during an infusion of
alcohol. It will also study how changes in brain chemistry relate to participant reports of
feeling drunk.
Objectives:
- To use magnetic resonance imaging to measure the effect of alcohol on brain chemistry
Eligibility:
- Individuals between 21 and 45 years of age.
- Participants will be either light drinkers (1 to 14 standard alcoholic drinks per week)
or heavy drinkers (20 to 40 standard alcoholic drinks per week). A standard drink is a
12-ounce beer, a 4-ounce glass of wine, or a shot of liquor.
- Participants must be able to go without alcohol for at least 3 days in a row without
severe withdrawal symptoms.
Design:
- This study requires two or three outpatient visits to the NIH Clinical Center.
- Participants will have a physical exam and medical history. Blood and urine samples will
be collected. Participants' alcohol drinking habits will also be assessed to determine
whether they may have an alcohol use disorder.
- At the first study visit, participants will have an infusion of alcohol. Blood samples
will be collected to measure blood alcohol levels.
- The MRI study visit will take place about 3 days after the first study visit.
Participants will have an MRI scan of the brain, followed by an infusion of alcohol and
another scan. Blood samples will be collected.
- Participants will complete questionnaires before and after each infusion to measure
their response to alcohol.
- Heavy drinkers will come to the clinic for a third visit to discuss possible future
treatment and any risky behavior associated with their high levels of alcohol use.
Rodent studies have indicated that modulation of glutamatergic transmission contributes to
alcohol intoxication, reinforcement, tolerance, and dependence. Brain microdialysis studies
have in general shown that acute alcohol suppresses glutamate release, while alcohol
withdrawal leads to progressively increased extracellular levels.
Here, we will use an acute, pharmacokinetically controlled alcohol challenge and magnetic
resonance spectroscopy (MRS) to study the relationship between brain alcohol and glutamate
concentrations, and correlate these with subjective feelings of alcohol effects, as measured
by the Drug Effects Questionnaire (DEQ) in human subjects. Correlations between MRS data and
other behavioral data from the Sensitivity to Punishment and Sensitivity to Reward
Questionnaire (SPSRQ), Alcohol Sensitivity Questionnaire (ASQ), and the Alcohol Effects
Questionnaire (AEFQ) will be investigated.
Healthy participants aged 21-45, without gross impairment of judgment or complicated
psychiatric or other morbidity, will receive a preliminary infusion to ensure no adverse
effects from intravenous (IV) alcohol administration to a target BAC of 0.08g/dl. In a
subsequent session, participants will be infused with alcohol to the same target level while
being scanned in the MR scanner and reporting subjective feelings using the DEQ. Two groups
of subjects will be recruited: heavy drinkers, classified as females who consume 15 plus
drinks per week and males who consume 20 plus drinks per weekthose who consume between 20 and
40 drinks per week, and light drinkers, classified as females who consume between 1 and 10
drinks per week and males who consume between 1 and 14 drinks per week. those who consume
between 1 and 14 drinks per week.
Central glutamate levels will be quantified at 3T using pharmacologically validated MRS
methodology recently published from our laboratory, and its relationship to central alcohol
levels will be determined. Relationships will also be analyzed between DEQ scores and brain
glutamate and alcohol levels. Finally, it will be examined whether drinking history (i.e.
being a light versus heavy drinker) is a moderator of any of these relationships.
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