A1 Refereed original research article in a scientific journal
Decreased Cannabinoid CB1 Receptors in Male Tobacco Smokers Examined With Positron Emission Tomography
Authors: Jussi Hirvonen, Paolo Zanotti-Fregonara, David A. Gorelick, Chul Hyoung Lyoo, Denise Rallis-Frutos, Cheryl Morse, Sami S. Zoghbi, Victor W. Pike, Nora D. Volkow, Marilyn A. Huestis, Robert B. Innis
Publisher: ELSEVIER SCIENCE INC
Publication year: 2018
Journal: Biological Psychiatry
Journal name in source: BIOLOGICAL PSYCHIATRY
Journal acronym: BIOL PSYCHIAT
Volume: 84
Issue: 10
First page : 715
Last page: 721
Number of pages: 7
ISSN: 0006-3223
eISSN: 1873-2402
DOI: https://doi.org/10.1016/j.biopsych.2018.07.009
Abstract
BACKGROUND: Previous studies showed reduction of brain cannabinoid CB1 receptors in adults with cannabis and alcohol use disorders. Preclinical data suggest that these receptors also contribute to nicotine reward and dependence. Tobacco smoking may confound clinical studies of psychiatric disorders because many patients with such disorders smoke tobacco. Whether human subjects who smoke tobacco but are otherwise healthy have altered CB1 receptor binding in brain is unknown.METHODS: We measured CB1 receptors in brains of 18 healthy men who smoke tobacco (frequent chronic cigarette smokers), and 28 healthy men who do not smoke tobacco, using positron emission tomography and [F-18]FMPEP-d(2), a radioligand for CB1 receptors. We collected arterial blood samples during scanning to calculate the distribution volume (V-T), which is nearly proportional to CB1 receptor density. Repeated-measures analysis of variance compared V-T between groups in various brain regions.RESULTS: Brain CB1 receptor V-T was about 20% lower in subjects who smoke tobacco than in subjects who do not. Decreased V-T was found in all brain regions, but reduction did not correlate with years of smoking, number of cigarettes smoked per day, or measures of nicotine dependence.CONCLUSIONS: Tobacco-smoking healthy men have a widespread reduction of CB1 receptor density in brain. Reduction of CB1 receptors appears to be a common feature of substance use disorders. Future clinical studies on the CB1 receptor should control for tobacco smoking.
BACKGROUND: Previous studies showed reduction of brain cannabinoid CB1 receptors in adults with cannabis and alcohol use disorders. Preclinical data suggest that these receptors also contribute to nicotine reward and dependence. Tobacco smoking may confound clinical studies of psychiatric disorders because many patients with such disorders smoke tobacco. Whether human subjects who smoke tobacco but are otherwise healthy have altered CB1 receptor binding in brain is unknown.METHODS: We measured CB1 receptors in brains of 18 healthy men who smoke tobacco (frequent chronic cigarette smokers), and 28 healthy men who do not smoke tobacco, using positron emission tomography and [F-18]FMPEP-d(2), a radioligand for CB1 receptors. We collected arterial blood samples during scanning to calculate the distribution volume (V-T), which is nearly proportional to CB1 receptor density. Repeated-measures analysis of variance compared V-T between groups in various brain regions.RESULTS: Brain CB1 receptor V-T was about 20% lower in subjects who smoke tobacco than in subjects who do not. Decreased V-T was found in all brain regions, but reduction did not correlate with years of smoking, number of cigarettes smoked per day, or measures of nicotine dependence.CONCLUSIONS: Tobacco-smoking healthy men have a widespread reduction of CB1 receptor density in brain. Reduction of CB1 receptors appears to be a common feature of substance use disorders. Future clinical studies on the CB1 receptor should control for tobacco smoking.
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