Nicotine is thought to exert its effects on the brain by binding to receptors in the brain called nicotinic acetylcholine receptors (nAChRs). However, tobacco smoke contains thousands of chemicals besides nicotine, some of which may also bind to the nAChRs or cause molecules normally found in the body to bind to these receptors. To study the effects of denicotinized cigarettes—cigarettes from which nicotine has been removed—on a specific type of nAChR (a4b2* nAChRs), researchers funded in part by NIDA used a brain imaging technique known as positron emission tomography (PET) to visualize these receptors in the brains of smokers during withdrawal and after smoking either low-nicotine or denicotinized cigarettes. Before the PET imaging, all volunteers stopped smoking for approximately 2 days. The volunteers underwent an hour of PET imaging while still undergoing withdrawal and then were assigned to perform one of three activities: smoke a low-nicotine cigarette, smoke a denicotinized cigarette, or not smoke; they then underwent approximately 4 more hours of PET imaging. Withdrawal symptoms were monitored during all imaging sessions. The imaging results showed not only that “inhalation of nicotine during cigarette smoking is solely responsible for occupancy of brain a4b2* nAChRs,” but also that the imaging “demonstrated significant a4b2* nAChR occupancy from smoking a denicotinized cigarette,” state the authors. This result challenges the assumption that denicotinized cigarettes do not affect the brain’s nicotine receptors, the authors further explain. Interestingly, whether or not the receptors were occupied did not correlate with withdrawal symptoms, indicating that factors other than nicotine binding to the receptors play a role in the relief of withdrawal symptoms provided by smoking.

Source: Brody et al. Brain nicotinic acetylcholine receptor occupancy: Effect of smoking a denicotinized cigarette. Int J Neuropsychopharmacol. 2009;12(3):305–316.