Dopamine Release in the Human Brain Following Alcohol Administration

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

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).

Study Overview

• Status: Completed
• Conditions: Heavy Drinking
• Intervention / Treatment: Drug: alcoholic beverage; Drug: non-alcoholic beverage

Detailed Description

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
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 1R8
      • Centre for Addiction and Mental Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: alcoholic beverage; 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; 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.; Other Names: Ethyl alcohol 95%
Placebo Comparator: non-alcoholic beverage; Orange juice and tonic water.	Drug: non-alcoholic beverage; This beverage will be a mixture of orange juice and tonic water. The beverage will be consumed over a period of 15 minutes.; Other Names: Tropicana orange juice and Schweppes tonic water.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Centre for Addiction and Mental Health

Publications and helpful links

Helpful Links

• Link Text: Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: June 28, 2012
• First Submitted That Met QC Criteria: July 9, 2012
• First Posted (Estimate): July 11, 2012

Study Record Updates

• Last Update Posted (Estimate): July 28, 2015
• Last Update Submitted That Met QC Criteria: July 27, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Ethanol
• Other Study ID Numbers: 041/2012