Decreased Cannabinoid CB1 Receptors in Male Tobacco Smokers Examined With Positron Emission Tomography

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

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)715-721
Number of pages7
JournalBiological Psychiatry
Issue number10
Publication statusPublished - 2018 Nov 15

Bibliographical note

Funding Information:
This research was supported by the Intramural Research Programs of the National Institute of Mental Health (Project Nos. ZIAMH002852 [to RBI] and ZIAMH002793 [to VWP]) and National Institute on Drug Abuse (NIDA) (Project No. DA000413 [to MAH]) under Clinical Protocol NCT00816439. JH was supported by personal grants from the Academy of Finland, Finnish Cultural Foundation, Finnish Foundation for Alcohol Studies, Finnish Medical Foundation, Instrumentarium Foundation, Jalmari and Rauha Ahokas Foundation, Paulo Foundation, Research Foundation of Orion Corp., and Yrjö Jahnsson Foundation.

Publisher Copyright:
© 2018 Society of Biological Psychiatry

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry


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