Jussi Hirvonen1, Paolo Zanotti-Fregonara2, David A Gorelick3, Chul Hyoung Lyoo4, Denise Rallis-Frutos4, Cheryl Morse4, Sami S Zoghbi4, Victor W Pike4, Nora D Volkow5, Marilyn A Huestis6, Robert B Innis4. 1. Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland; Department of Radiology, University of Turku, Turku, Finland. Electronic address: jussi.hirvonen@utu.fi. 2. Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland; Houston Methodist Research Institute, Houston, Texas. 3. Chemistry and Drug Metabolism Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland; Department of Psychiatry, School of Medicine, University of Maryland, Baltimore, Maryland. 4. Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland. 5. Office of the Director, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland. 6. Chemistry and Drug Metabolism Section, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland; Lambert Center for the Study of Medicinal Cannabis and Hemp, Thomas Jefferson University, Philadelphia, Pennsylvania.
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 [18F]FMPEP-d2, a radioligand for CB1 receptors. We collected arterial blood samples during scanning to calculate the distribution volume (VT), which is nearly proportional to CB1 receptor density. Repeated-measures analysis of variance compared VT between groups in various brain regions. RESULTS: Brain CB1 receptor VT was about 20% lower in subjects who smoke tobacco than in subjects who do not. Decreased VT 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 cannabinoidCB1 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 [18F]FMPEP-d2, a radioligand for CB1 receptors. We collected arterial blood samples during scanning to calculate the distribution volume (VT), which is nearly proportional to CB1 receptor density. Repeated-measures analysis of variance compared VT between groups in various brain regions. RESULTS: Brain CB1 receptor VT was about 20% lower in subjects who smoke tobacco than in subjects who do not. Decreased VT 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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