TY - JOUR T1 - Decreased brain cannabinoid CB1 receptor binding in tobacco smokers examined with positron emission tomography JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 84 LP - 84 VL - 55 IS - supplement 1 AU - Jussi Hirvonen AU - Paolo Zanotti-Fregonara AU - David Gorelick AU - Denise Rallis-Frutos AU - Cheryl Morse AU - Sami Zoghbi AU - Victor Pike AU - Marilyn Huestis AU - Robert Innis Y1 - 2014/05/01 UR - http://jnm.snmjournals.org/content/55/supplement_1/84.abstract N2 - 84 Objectives Cannabinoid CB1 receptors are involved in the rewarding effects of nicotine, and tobacco smoking may confound clinical studies. We previously found reduction of brain cannabinoid CB1 receptor binding in both cannabis abuse and alcohol dependence. In this study, we tested whether tobacco smokers have reduced cannabinoid CB1 receptor binding, using positron emission tomography (PET) with [18F]FMPEP-d2, a radioligand for CB1 receptors. Methods We measured CB1 receptors in 13 healthy male subjects who smoked tobacco (age 35 ± 9 years), and in 31 healthy male subjects who did not smoke (or have smoked) tobacco (age 33 ± 10 years). Smokers had an average Fagerström Test for Nicotine Dependence score of 4 (mild to moderate nicotine addiction) and smoked an average of 14 cigarettes per day (range: 1-20). We sampled arterial blood during PET scans to estimate receptor binding as distribution volume (VT). Results VT of [18F]FMPEP-d2 was about 20% lower in tobacco smokers than in non-smokers throughout the brain (main effect of smoking: F=5.9, p=0.020; smoking by region interaction: F=2.6, p=0.055). The plasma free fraction of [18F]FMPEP-d2 was similar between smokers (0.45%) and non-smokers (0.41%). Among smokers, VT did not correlate with number of cigarettes smoked per day (R=-0.14, p=0.64), lifetime duration of tobacco smoking (R=0.29, p=0.33), age at onset of tobacco smoking (R=0.19, p=0.54), or Fagerström score (R=0.46, p=0.14). Conclusions Tobacco smoking is associated with a reduction of cannabinoid CB1 receptors. This reduction occurred throughout the brain, in contrast to regionally specific downregulation in cannabis smoking, and was smaller in magnitude than that in patients with alcohol dependence. Future clinical studies on the CB1 receptor should control for tobacco smoking. Research Support Intramural Research Program, NIH, National Institute of Mental Health and National Institute on Drug Abuse. ER -