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, Chulhyoung 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

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Cannabinoids
Positron-Emission Tomography
Alcoholism
Alcohols
Brain
Drinking
Alleles
Genes

All Science Journal Classification (ASJC) codes

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

Cite this

Hirvonen, J., Zanotti-Fregonara, P., Umhau, J. C., George, D. T., Rallis-Frutos, D., Lyoo, C., ... 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
Hirvonen, J. ; Zanotti-Fregonara, P. ; Umhau, J. C. ; George, D. T. ; Rallis-Frutos, D. ; Lyoo, Chulhyoung ; Li, C. T. ; Hines, C. S. ; Sun, H. ; Terry, G. E. ; Morse, C. ; Zoghbi, S. S. ; Pike, V. W. ; Innis, R. B. ; Heilig, M. / Reduced cannabinoid CB 1 receptor binding in alcohol dependence measured with positron emission tomography. In: Molecular Psychiatry. 2013 ; Vol. 18, No. 8. pp. 916-921.
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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.",
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Hirvonen, J, Zanotti-Fregonara, P, Umhau, JC, George, DT, Rallis-Frutos, D, Lyoo, C, Li, CT, Hines, CS, Sun, H, Terry, GE, Morse, C, Zoghbi, SS, Pike, VW, Innis, RB & Heilig, M 2013, 'Reduced cannabinoid CB 1 receptor binding in alcohol dependence measured with positron emission tomography', Molecular Psychiatry, vol. 18, no. 8, pp. 916-921. https://doi.org/10.1038/mp.2012.100

Reduced cannabinoid CB 1 receptor binding in alcohol dependence measured with positron emission tomography. / Hirvonen, J.; Zanotti-Fregonara, P.; Umhau, J. C.; George, D. T.; Rallis-Frutos, D.; Lyoo, Chulhyoung; Li, C. T.; Hines, C. S.; Sun, H.; Terry, G. E.; Morse, C.; Zoghbi, S. S.; Pike, V. W.; Innis, R. B.; Heilig, M.

In: Molecular Psychiatry, Vol. 18, No. 8, 01.08.2013, p. 916-921.

Research output: Contribution to journalArticle

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AU - Hirvonen, J.

AU - Zanotti-Fregonara, P.

AU - Umhau, J. C.

AU - George, D. T.

AU - Rallis-Frutos, D.

AU - Lyoo, Chulhyoung

AU - Li, C. T.

AU - Hines, C. S.

AU - Sun, H.

AU - Terry, G. E.

AU - Morse, C.

AU - Zoghbi, S. S.

AU - Pike, V. W.

AU - Innis, R. B.

AU - Heilig, M.

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