Brain accumulation rate and magnitude are critical for the acute reinforcing effects of nicotine. Despite electronic cigarettes' (E-cigs) appeal as substitutes for traditional combustible cigarettes (C-cigs), brain nicotine accumulation (BNA) from E-cigs has not been compared with that from C-cigs using a within-subjects design. BNA was directly assessed with 16 adult dual users (10 females) of E-cigs (e-liquid pH 9.4) and C-cigs, using 11C-nicotine and positron emission tomography (PET). Participants went through two 15-min head scanning sessions during which they inhaled a single puff of E-cig vapor or C-cig smoke containing 11C-nicotine in a randomized order. A full-body scan was also conducted at each session to measure total absorbed dose of 11C-nicotine. Mean maximum concentration (Cmax) and area under curve of BNA were 22.1% and 22.7% lower, respectively, following E-cig compared with C-cig inhalation. Meanwhile, T1/2 was 2.7 times longer following inhalation of E-cig vapor relative to C-cig smoke (all ps < 0.005). Whole-body imaging indicated greater nicotine retention in the respiratory tract from vapor versus smoke inhalation (p < 0.0001). Following vapor inhalation, nicotine retention in the respiratory tract was correlated with Cmax values of BNA (rs = -0.59, p < 0.02). Our results confirm that E-cigs with alkaline pH e-liquid can deliver nicotine rapidly to the brain, albeit less efficiently than C-cigs partly due to greater airway retention of nicotine. Since brain nicotine uptake mediates reinforcement, these results help elucidate actions of E-cigs in terms of abuse liability and effectiveness in substituting for combustible cigarettes.
© 2022. The Author(s), under exclusive licence to American College of Neuropsychopharmacology.