Protocol Number: 09-M-0040
The brain endocannabinoid (EC) system is a recently discovered brain neurotransmission system, which involves endogenous cannabinoid agents (ECs) that act upon specific receptors (CB1 and CB2). CB1 receptor is abundant in the human brain and acts as an inhibitory modulator of classical neurotransmitters. ECs and CB1 receptors appear to modulate the brain reward system, and animal studies have demonstrated an important role of CB1 receptor stimulation in alcohol- and drug-related behaviors. During chronic alcohol exposure, EC levels in the brain are elevated and CB1 receptor levels are consequently reduced; this appears to be reversible following withdrawal. Animal studies suggest that CB1 receptor blockade in the abstinent phase may reduce alcohol craving and relapse. To what extent ECs and CB1 receptors are involved in the pathophysiology of alcohol dependence in humans is currently unknown. The lack of suitable methods to reliably quantify CB1 receptors in the living human brain has to date hindered the progress in this field. In this protocol, we outline studies aiming at elucidating the role CB1 receptors in alcohol dependence by using positron emission tomography (PET) and the recently developed radiotracer for CB1 receptors, [11C]MePPEP. The aim of this project is to explore CB1 receptor abnormalities at various stages of alcohol dependence in humans. The primary hypothesis is that CB1 receptors are downregulated during chronic alcohol exposure and upregulated during protracted abstinence. Insight into the role of CB1 receptor function in human alcoholism may help guide future development of pharmacotherapies.
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National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 01/13/2009
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