Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
There is a need to better understand the mechanisms underlying alcohol use and dependence in order to advance the clinical treatment of alcohol dependence. Here, the investigators will use Positron Emission Tomography to determine if there is an up-regulation of D3 receptors in the brains of subjects with alcohol use disorders. The investigators will also investigate the relationship between D3 binding and major phenotypes associated with alcohol use disorders, namely: alcohol cue induced craving and motivation to self-administer alcohol in the laboratory.
Alcohol dependence is a devastating illness with social and medical costs estimated to be 180 billion dollars annually in the US. In the clinical treatment of alcoholism, reducing alcohol consumption in heavy drinkers is a major clinical challenge. As such, there has been much emphasis in both clinical and preclinical research to identify the substrates that mediate craving, excessive drinking and addiction. Identifying the neurobiological mechanisms of alcohol dependence may lead to the development of new and better treatment strategies. Preclinical studies indicate that the D3 receptor is involved in alcohol-cue response and in the motivation to drink alcohol. However, there is currently no data available in human subjects exploring the relationship between D3 and those behavioral responses in subjects with alcohol use disorders.
Aim #1: To measure the [11C]-(+)-PHNO PET binding levels in the brains of subjects with alcohol use disorders.
Aim #2: To determine the relationship between D3 receptor binding and alcohol cue induced craving and motivation to self-administer alcohol in the laboratory.
To achieve designated goals, the investigators will recruit 25 male and female subjects who are non-treatment seekers. After a period of abstinence from alcohol, participants will come to the Centre for Addiction of Mental Health for a [11C]-(+)-PHNO PET scan. Participants will also have additional sessions during which other alcohol-related measures will be assessed (i.e. alcohol cue induced craving and motivation to self-administer alcohol in the laboratory).
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental | Experimental | 5 experimental sessions per participant: (1) [11C]-(+)-PHNO PET scan, (2), Alcohol Self-Administration, (3) Craving Task, (4) MRI scan and (5) Neuropsychological Assessment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| [11C]-(+)-PHNO PET scan | Other | PET scan |
| |
| Alcohol Self-Administration |
| Measure | Description | Time Frame |
|---|---|---|
| Dopamine D2/D3 receptor occupancy | Dopamine D2/D3 receptor occupancy in the brains of individuals with Alcohol Use Disorders will be quantified using [11C]-(+)-PHNO Positron Emission Tomography (PET). [11C]-(+)-PHNO binding levels will be used to infer receptor occupancy. | One PET scan after 2-7 days of abstinence from alcohol; ~2 hours in duration. |
| Measure | Description | Time Frame |
|---|---|---|
| Alcohol craving ratings | Participants' ratings for alcohol craving acquired during the validated Cue-Induced Craving Paradigm (using the Alcohol Urge Questionnaire: 8 items on a 11-point Likert scale) will be correlated to dopamine receptor occupancy (outcome 1). | Cue paradigm session is expected to take ~1 hour and will occur on the PET day. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Bernard Le Foll, MD, PhD | Centre for Addiction and Mental Health | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre for Addiction and Mental Health | Toronto | Ontario | M5S2S1 | Canada |
Not provided
| Label | URL |
|---|---|
| Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital, fully affiliated with the University of Toronto, and a PAHO/WHO Collaborating Centre. | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Type | Date | Date Unknown |
|---|---|---|
| Release | Oct 6, 2023 | |
| Reset | Apr 5, 2024 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Other |
Session for assessing motivation for consuming alcohol. |
|
| Craving Task | Other | Cue exposure paradigm |
|
| MRI scan | Other | MRI scan scan to analyze the PET data will be administered. |
|
| Neuropsychological Assessment | Other | Cognitive questionnaires administered over course of study. |
|
| Effort to obtain alcohol | Laboratory alcohol self-administration paradigm in which participants press a button to intravenously self-administer small doses of alcohol will be used to assess amount of effort expended to obtain alcohol ("break point"). The # of button presses required to obtain the alcohol will increase as per the Progressive Ratio schedule. Regression analysis between effort and [11C]-(+)-PHNO binding (outcome 1) will be applied. | Single self-administration session will occur on its own day with a time commitment of ~6 hours. |
Not provided
| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Oct 6, 2023 | Apr 5, 2024 |
| ID | Term |
|---|---|
| D000437 | Alcoholism |
| ID | Term |
|---|---|
| D019973 | Alcohol-Related Disorders |
| D019966 | Substance-Related Disorders |
| D064419 | Chemically-Induced Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| ID | Term |
|---|---|
| D000431 | Ethanol |
| D009682 | Magnetic Resonance Spectroscopy |
| D009483 | Neuropsychological Tests |
| ID | Term |
|---|---|
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D013057 | Spectrum Analysis |
| D002623 | Chemistry Techniques, Analytical |
| D008919 | Investigative Techniques |
| D011581 | Psychological Tests |
| D004191 | Behavioral Disciplines and Activities |
Not provided
Not provided