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

doi:10.1038/mp.2012.100

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

Department of Neurology

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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 language	English
Pages (from-to)	916-921
Number of pages	6
Journal	Molecular Psychiatry
Volume	18
Issue number	8
DOIs	https://doi.org/10.1038/mp.2012.100
Publication status	Published - 2013 Aug

Bibliographical note

Funding Information:
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.

All Science Journal Classification (ASJC) codes

Molecular Biology
Psychiatry and Mental health
Cellular and Molecular Neuroscience

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/mp.2012.100

Cite this

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

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title = "Reduced cannabinoid CB 1 receptor binding in alcohol dependence measured with positron emission tomography",

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.",

author = "J. Hirvonen and P. Zanotti-Fregonara and Umhau, {J. C.} and George, {D. T.} and D. Rallis-Frutos and Lyoo, {C. H.} and Li, {C. T.} and Hines, {C. S.} and H. Sun and Terry, {G. E.} and C. Morse and Zoghbi, {S. S.} and Pike, {V. W.} and Innis, {R. B.} and M. Heilig",

note = "Funding Information: 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 Yrj{\"o} Jahnsson Foundation.",

year = "2013",

month = aug,

doi = "10.1038/mp.2012.100",

language = "English",

volume = "18",

pages = "916--921",

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Hirvonen, J, Zanotti-Fregonara, P, Umhau, JC, George, DT, Rallis-Frutos, D, Lyoo, CH, 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

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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, C. H.

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.

N1 - Funding Information: 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.

PY - 2013/8

Y1 - 2013/8

N2 - 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.

AB - 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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Reduced cannabinoid CB 1 receptor binding in alcohol dependence measured with positron emission tomography

Abstract

Bibliographical note

All Science Journal Classification (ASJC) codes

UN SDGs

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