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

Molecular Psychiatry volume 18, pages 916–921 (2013)Cite this article

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Abstract

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 [18F]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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Acknowledgements

We thank Kimberly Jenko, Kacey Anderson and David Clark for assisting in the measurements of radioligand in plasma; Maria D Ferraris Araneta, Gerald Hodges, William C Kreisl and Barbara Scepura as well as Chris Geyer and the NIAAA nursing staff for subject recruitment and care; the NIH PET Department for imaging; and the PMOD Technologies for providing its image analysis and modeling software. This research was supported by the Intramural Programs of NIMH and NIAAA. Jussi Hirvonen was supported by personal grants from The Academy of Finland; The Finnish Cultural Foundation; The Finnish Foundation for Alcohol Studies; The Finnish Medical Foundation; The Instrumentarium Foundation; The Jalmari and Rauha Ahokas Foundation; The Paulo Foundation; The Research Foundation of Orion Corporation; and The Yrjö Jahnsson Foundation.

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  1. P Zanotti-Fregonara, J C Umhau, R B Innis and M Heilig: These authors contributed equally to this work.

Authors and Affiliations

  1. Molecular Imaging Branch, National Institute of Mental Health, NIH, Bethesda, MD, USA,

    J Hirvonen, P Zanotti-Fregonara, D Rallis-Frutos, C H Lyoo, C-T Li, C S Hines, G E Terry, C Morse, S S Zoghbi, V W Pike & R B Innis

  2. Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA,

    J C Umhau, D T George, H Sun & M Heilig

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  1. J Hirvonen
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Correspondence to M Heilig.

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Hirvonen, J., Zanotti-Fregonara, P., Umhau, J. et al. Reduced cannabinoid CB1 receptor binding in alcohol dependence measured with positron emission tomography. Mol Psychiatry 18, 916–921 (2013). https://doi.org/10.1038/mp.2012.100

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