Dopamine Release in the Human Brain Following Alcohol Administration

Study Overview
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Brief Summary
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The purpose of this study is to examine whether there is an increase in dopamine levels in the human striatum following an oral administration of alcohol, as has been evidenced in animal models. This will be a Positron Emission Tomography (PET) study using the radiotracer, [11C]-(+)-PHNO (11C]-( + )-4-propyl- 3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol).

Detailed Description
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This will be a within subjects study in 8 heavy drinkers ages 21-45. The within factors will be PET scans following an alcoholic beverage and following a non-alcoholic beverage. Participants will also have a baseline session prior to the scans where they will complete various cognitive tasks and questionnaires. During each PET scan, subjective drug effects as well as heart rate, blood pressure, blood alcohol content and cortisol levels will be collected. The change in PHNO binding potential between the two scan conditions will be the primary outcome measure.

Official Title
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Imaging Alcohol Induced Dopamine Release in the Human Brain: a PET/[11C](+)PHNO Study

Conditions
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Heavy Drinking

Intervention / Treatment
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* Drug: alcoholic beverage
* Drug: non-alcoholic beverage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males and females of any ethnic origin between 21 and 45 years old. Reported consumption of at least two heavy drinking episodes (according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) criterion of 5 drinks for males or 4 for females) in the past 30 days prior to assessment. Willing and capable to provide written informed consent Good command of the English language Exclusion Criteria: Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnosis of alcohol dependence; receiving treatment for alcohol dependence Taking medications or have any medical condition for which alcohol is contraindicated Any medical condition requiring immediate investigation or treatment Previous head trauma/neurological condition such as clinically significant history of seizure disorder, a history of clinically significant head trauma (i.e., concussion resulting in clinically significant loss of consciousness) or past intracranial surgery Beck Depression Inventory score >16 Current active or past suicidal ideation Pregnancy tested by urine and blood screen each PET study day or lactation Current DSM-IV diagnosis of any Axis I psychiatric disorder Regular use of any therapeutic or recreational psychoactive drug use during the last three months (with the exception of nicotine and alcohol) or other substance use disorder (including nicotine) Abnormal body mass (as defined as not within 20% of normal body mass index). Current past or anticipated exposure to radiation exceeding 20 mSv in the last year. Metal implants or paramagnetic objects within the body which may interfere with the magnetic resonance imaging (MRI). Claustrophobia or a history of panic attacks Abnormal clinical laboratory findings including serum creatinine greater than 2.0 mg/dl, abnormal liver function tests, elevated serum bilirubin (more than 1.5 times upper limit of normal), or pre-trial electrocardiogram (EKG) results demonstrating clinical significant abnormality

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: alcoholic beverage<br>95% USP alcohol given at a dose of 1.5 g/l of body water mixed with orange juice and tonic water. | Drug: alcoholic beverage<br>* An appropriate amount of 95% USP ethyl alcohol will be mixed in orange juice and tonic water to obtain a drink equivalent to 3-5 standard drinks. The beverage will be consumed over a period of 15 minutes.<br>* Other names: Ethyl alcohol 95%;|
| Placebo Comparator: non-alcoholic beverage<br>Orange juice and tonic water. | Drug: non-alcoholic beverage<br>* This beverage will be a mixture of orange juice and tonic water. The beverage will be consumed over a period of 15 minutes.<br>* Other names: Tropicana orange juice and Schweppes tonic water.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PHNO Binding Potential | Following the injection of the positron-emitting radiotracer [11C]-(+)-PHNO, binding of this radiotracer to dopamine receptors (DR) D2/3 will be measured using the PET scanner. As dopamine also binds to DR D2/3, either an increase or decrease in dopamine levels will either decrease or increase PHNO occupancy respectively. [11C]-(+)-PHNO binding potential will be measured on two different conditions (alcoholic beverage vs non-alcoholic beverage) on two separate days. | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective effects of alcohol | During the PET scans, the subjective effects ( Alcohol Urges Scale, Biphasic Alcohol Effects Scale)of alcohol will be assessed at various time points throughout beverage consumption and PET scan. | 2 weeks | 
| Objective effects of alcohol | During the PET scans, the objective effects of alcohol (blood pressure, heart rate, blood alcohol content, blood cortisol levels) will be assessed at various time points throughout the drink consumption and PET scan. | 2 weeks |