Dopamine Release in the Human Brain Following Alcohol Administration

Centre for Addiction and Mental Health8 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Heavy Drinking

Interventions

alcoholic beverageDRUG

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.

non-alcoholic beverageDRUG

This beverage will be a mixture of orange juice and tonic water. The beverage will be consumed over a period of 15 minutes.

Eligibility

Sex: ALLMin age: 21 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Centre for Addiction and Mental Health

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

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.

Time frame: 2 weeks

Secondary Outcomes

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.

Time frame: 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.

Time frame: 2 weeks

Data from ClinicalTrials.gov

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