Investigative analysis of blood-brain barrier penetrating potential of electronic nicotine delivery systems (e-cigarettes) chemicals using predictive computational models.

Introduction: Seizures are known potential side effects of nicotine toxicity and have been reported in electronic nicotine delivery systems (ENDS, e-cigarettes) users, with the majority involving youth or young adults.

Areas covered: Using chemoinformatic computational models, chemicals (including flavors) documented to be present in ENDS were compared to known neuroactive compounds to predict the blood-brain barrier (BBB) penetration potential, central nervous system (CNS) activity, and their structural similarities. The literature search used PubMed/Google Scholar, through September 2023, to identify individual chemicals in ENDS and neuroactive compounds.The results show that ENDS chemicals in this study contain >60% structural similarity to neuroactive compounds based on chemical fingerprint similarity analyses. The majority of ENDS chemicals we studied were predicted to cross the BBB, with approximately 60% confidence, and were also predicted to have CNS activity; those not predicted to passively diffuse through the BBB may be actively transported through the BBB to elicit CNS impacts, although it is currently unknown.

Expert opinion: In lieu of in vitro and in vivo testing, this study screens ENDS chemicals for potential CNS activity and predicts BBB penetration potential using computer-based models, allowing for prioritization for further study and potential early identification of CNS toxicity.