Measuring Effects of Alcohol on Brain Chemistry
- 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.
- To use magnetic resonance imaging to measure the effect of alcohol on brain chemistry
- 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.
- 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.
|Study Design:||Time Perspective: Cross-Sectional|
|Official Title:||Measuring Effects of Acute Ethanol on Human Brain Metabolites Using Magnetic Resonance Spectroscopy|
- What is the correlation between measured blood and breath alcohol level and ethanol level concentration computed from MRS. [ Time Frame: End of study ] [ Designated as safety issue: No ]
- Does ethanol administration similarly affect the metabolite activities in all the regions of the brain Gray and White matter? [ Time Frame: End of study ] [ Designated as safety issue: No ]
- Measure: Does ethanol metabolite concentration correlate with any of subjective effects of ethanol as measured by response to DEQ questions? [ Time Frame: End of study ] [ Designated as safety issue: No ]
|Study Start Date:||November 2011|
|Estimated Study Completion Date:||February 2015|
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01492933
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Reza Momenan, Ph.D.||National Institute on Alcohol Abuse and Alcoholism (NIAAA)|