Alcohol dependence (AD) is a US public health and safety concern, urging improved treatment approaches such as targeted pharmacotherapies. Preclinical and postmortem data have provided evidence that endocannabinoid signaling may play a role in the initiation and maintenance of alcohol abuse. In this regard, converging data suggest that the metabolizing enzyme, Fatty Acide Amide Hydrolase (FAAH) is deficient in AD; however no in vivo clinical data exist. Our center has recently developed a positron emission tomography (PET) imaging probe, [11C]CURB, which enables measuring FAAH activity in vivo. We have recently shown that brain [11C]CURB binding can be reliably measured in the human, making it possible, for the first time, to measure endocannabinoid metabolism directly in humans with addictive disorders. Here, we will test the hypothesis that FAAH activity is decreased in alcohol dependent patients in early and protracted abstinence relative to control subjects without alcohol use disorder. Fifteen subjects with AD will be scanned with [11C]CURB within 3-7 days of admission from on-going drinking and after 2-4 weeks of supervised abstinence. Healthy controls will be scanned once. Behavioral and demographic information will be recorded and an MRI will be acquired for PET image co-registration. If FAAH activity is shown to be reduced in AD, this would demonstrate an endocannabinoid elevating process that may contribute to both, risk for AD and key features of alcohol use. This could lead to developing therapeutic strategies for prevention and treatment of AD.

Public Health Relevance

Fatty Acid Amide Hydrolase is the enzyme that regulates brain levels of the endocannabinoid, anadamide, and it is a uniquely interesting target for the development of therapeutics for alcohol dependence and other addictions. The present brain imaging project will determine for the first time in human, the level of this enzyme in individual with alcohol dependence.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AA022246-01A1
Application #
8636311
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Matochik, John A
Project Start
2014-02-01
Project End
2016-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
1
Fiscal Year
2014
Total Cost
$140,210
Indirect Cost
$10,386
Name
Centre for Addiction and Mental Health
Department
Type
DUNS #
207855271
City
Toronto
State
ON
Country
Canada
Zip Code
M5S2S-1