Decreased Cannabinoid CB 1 Receptors in Male Tobacco Smokers Examined With Positron Emission Tomography

摘要

BackgroundPrevious studies showed reduction of brain cannabinoid CB1receptors 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 CB1receptor binding in brain is unknown. MethodsWe measured CB1receptors 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 CB1receptors. We collected arterial blood samples during scanning to calculate the distribution volume (VT), which is nearly proportional to CB1receptor density. Repeated-measures analysis of variance comparedVTbetween groups in various brain regions. ResultsBrain CB1receptorVTwas about 20% lower in subjects who smoke tobacco than in subjects who do not. DecreasedVTwas 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. ConclusionsTobacco-smoking healthy men have a widespread reduction of CB1receptor density in brain. Reduction of CB1receptors appears to be a common feature of substance use disorders. Future clinical studies on the CB1receptor should control for tobacco smoking.