Reduced cannabinoid CB 1 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

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Abstract

Brain cannabinoid CB 1 receptors contribute to alcohol-related behaviors in experimental animals, but their potential role in humans with alcohol dependence is poorly understood. We measured CB 1 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-d 2, a radioligand for CB 1 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 CB 1 receptor gene (CNR1) that may moderate CB 1 receptor density. On the first scan, CB 1 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, CB 1 receptor binding remained similarly reduced in these patients. Irrespective of the diagnostic status, C allele carriers at rs2023239 had higher CB 1 receptor binding compared with non-carriers. Alcohol dependence is associated with a widespread reduction of cannabinoid CB 1 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 CB 1 receptors in alcohol dependence in humans.

Original languageEnglish
Pages (from-to)916-921
Number of pages6
JournalMolecular Psychiatry
Volume18
Issue number8
DOIs
Publication statusPublished - 2013 Aug 1

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    Hirvonen, J., Zanotti-Fregonara, P., Umhau, J. C., George, D. T., Rallis-Frutos, D., Lyoo, C. H., Li, C. T., Hines, C. S., Sun, H., Terry, G. E., Morse, C., Zoghbi, S. S., Pike, V. W., Innis, R. B., & Heilig, M. (2013). Reduced cannabinoid CB 1 receptor binding in alcohol dependence measured with positron emission tomography. Molecular Psychiatry, 18(8), 916-921. https://doi.org/10.1038/mp.2012.100