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Reduced cannabinoid CB1 receptor binding in alcohol dependence measured with positron emission tomography

 J Hirvonen  ;  P Zanotti-Fregonara  ;  J C Umhau  ;  D T George  ;  D Rallis-Frutos  ;  C H Lyoo  ;  C-T Li  ;  C S Hines  ;  H Sun  ;  G E Terry  ;  C Morse  ;  S S Zoghbi  ;  V W Pike  ;  R B Innis  ;  M Heilig 
 MOLECULAR PSYCHIATRY, Vol.18(8) : 916-921, 2013 
Journal Title
Issue Date
Adult ; Alcoholism/diagnostic imaging ; Alcoholism/metabolism* ; Alleles ; Brain/diagnostic imaging ; Brain/metabolism* ; Case-Control Studies ; Functional Neuroimaging ; Humans ; Male ; Radionuclide Imaging ; Receptor, Cannabinoid, CB1/genetics* ; Receptor, Cannabinoid, CB1/metabolism*
alcohol dependence ; cannabinoid CB1 receptor ; endocannabinoid ; imaging ; positron emission tomography
Brain cannabinoid CB1 receptors contribute to alcohol-related behaviors in experimental animals, but their potential role in humans with alcohol dependence is poorly understood. We measured CB1 receptors in alcohol dependent patients in early and protracted abstinence, and in comparison with control subjects without alcohol use disorders, using positron emission tomography and [(18)F]FMPEP-d2, a radioligand for CB1 receptors. We scanned 18 male in-patients with alcohol dependence twice, within 3-7 days of admission from ongoing drinking, and after 2-4 weeks of supervised abstinence. Imaging data were compared with those from 19 age-matched healthy male control subjects. Data were also analyzed for potential influence of a common functional variation (rs2023239) in the CB1 receptor gene (CNR1) that may moderate CB1 receptor density. On the first scan, CB1 receptor binding was 20-30% lower in patients with alcohol dependence than in control subjects in all brain regions and was negatively correlated with years of alcohol abuse. After 2-4 weeks of abstinence, CB1 receptor binding remained similarly reduced in these patients. Irrespective of the diagnostic status, C allele carriers at rs2023239 had higher CB1 receptor binding compared with non-carriers. Alcohol dependence is associated with a widespread reduction of cannabinoid CB1 receptor binding in the human brain and this reduction persists at least 2-4 weeks into abstinence. The correlation of reduced binding with years of alcohol abuse suggests an involvement of CB1 receptors in alcohol dependence in humans.
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1. College of Medicine (의과대학) > Dept. of Neurology (신경과학교실) > 1. Journal Papers
Yonsei Authors
Lyoo, Chul Hyoung(류철형) ORCID logo https://orcid.org/0000-0003-2231-672X
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