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Comparison of brain nicotine uptake from electronic cigarettes and combustible cigarettes

Abstract

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.

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Fig. 1: Average brain nicotine accumulation curves (±SE) after inhalation of a single puff of vapor from an E-cig and single puff of smoke from a C-cig (n = 16).
Fig. 2: Kinetic parameters (mean + SEM) of brain nicotine accumulation after inhalation of a single puff of E-cig vapor and C-cig smoke in dual users (n = 16).
Fig. 3: Oropharyngeal and tracheobronchial deposition of nicotine after use of C-cig and E-cig (left panels).
Fig. 4: Respiratory tract (RT) retention of nicotine after use of E-cig and C-cig and its association with Cmax of brain nicotine accumulation following E-cig vapor inhalation.

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Acknowledgements

We thank Sandra Norona, Allison Fulp, and Jonathan Richardson for assistance in data acquisition.

Funding

Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number R01DA044756. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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All authors contributed to drafting the work or revising it critically for important intellectual content, gave final approval of the version to be published; and provided an agreement to be accountable for all aspects of the work. In addition: YZ provided contributions to the conception, the data acquisition, analysis and interpretation, and wrote the manuscript draft; AGM - the study concept and design, data acquisition, analysis and interpretation, and the project supervision; HB and JDM - data analysis and contributions to data acquisition and interpretation; AM provided contributions to the study concept and design; JER provided contributions to the study concept and data interpretation; KKSS provided contributions to the study conception, data acquisition and the project supervision.

Corresponding author

Correspondence to Alexey G. Mukhin.

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Competing interests

AGM discloses grants from the National Institute on Drug Abuse and consulting for Rose Research Center LLC on the project funded by Philip Morris International, outside the submitted work. JER discloses grants from the National Institute on Drug Abuse, research support from Foundation for a Smoke-Free World, Philip Morris International, Altria, JUUL Labs, consulting with Revive pharmaceuticals, and consulting and patent purchase agreement with Philip Morris International, related to smoking cessation and tobacco harm reduction. All other authors declare no competing interests.

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Zuo, Y., Mukhin, A.G., Berg, H. et al. Comparison of brain nicotine uptake from electronic cigarettes and combustible cigarettes. Neuropsychopharmacol. 47, 1939–1944 (2022). https://doi.org/10.1038/s41386-022-01410-5

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