Neurotoxic Effects of Electronic Cigarette Exposure on the Central Nervous System: A Scoping Review

Abstract

Electronic cigarettes (e-cigarettes) have achieved global adoption, with an estimated 82 million users worldwide and disproportionate uptake among adolescents. Despite marketing as a safer tobacco alternative, e-cigarette aerosols contain neurotoxic constituents including nicotine, flavoring agents, carbonyl compounds, and heavy metals. This review maps empirical evidence on CNS effects of e-cigarette exposure across biological model types. A systematic scoping review was conducted per the Arksey and O'Malley framework and reported per PRISMA-ScR guidelines. PubMed and Scopus were searched in January 2026 for studies from 2015 to 2026 examining quantifiable CNS outcomes following e-cigarette exposure in human, animal, or in vitro models. Data were extracted across eight domains and synthesized narratively. Seventy-four studies met inclusion criteria: 49 animal in vivo (66.2%), 17 human (23.0%), and 8 in vitro (10.8%), spanning 14 countries. Seven CNS outcome domains were identified: neuroinflammation and oxidative stress, blood-brain barrier (BBB) integrity, cognitive and behavioral outcomes, neuroimaging and pharmacokinetics, neurotransmitter systems and electrophysiology, developmental neurotoxicology, and other outcomes. Neuroinflammation and BBB disruption showed high directional consistency. Cognitive impairment, hippocampal volume reductions, and reward circuit reorganization were consistently observed. Developmental studies identified epigenomic reprogramming and disrupted GABAergic interneuron migration. Non-nicotine constituents were independently implicated in CNS toxicity. E-cigarette exposure is associated with a consistent and biologically plausible pattern of CNS harm. The developing brain represents a priority risk population given its heightened vulnerability to neurotoxic insult. Current evidence does not support the neurological safety of e-cigarettes; regulatory frameworks should mandate rigorous CNS-specific toxicity assessment for electronic nicotine delivery systems.

Keywords

• e-cigarettes
• central nervous system
• neurotoxicity
• neuroinflammation
• scoping review

Supporting Institution

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Ethical Statement

The author declares that this study complies with research and publication ethics. All procedures performed in this study were in accordance with the ethical standards of the relevant institutional and national committees and with the Helsinki Declaration of 1964 and its later amendments. No ethical approval was required for this study. The author has no conflicts of interest to declare.

Thanks

I would like to express my deepest gratitude to Dr. Cem Güler and Prof. Dr. Nefise Ülkü Karabay Yavaşoğlu for their invaluable academic guidance, mentorship, and the countless contributions they have made to my personal and professional development. Their support has been truly transformative. I am also sincerely grateful to my mother and sister, whose unconditional love and constant encouragement have been my greatest source of strength. Finally, I would like to thank my dear friends for their endless support, patience, and friendship throughout this journey.

Elektronik Sigara Maruziyetinin Merkezi Sinir Sistemi Üzerindeki Nörotoksik Etkileri: Bir Kapsam Derlemesi

Abstract

Electronic cigarettes (e-cigarettes) have achieved global adoption, with an estimated 82 million users worldwide and disproportionate uptake among adolescents. Despite marketing as a safer tobacco alternative, e-cigarette aerosols contain neurotoxic constituents including nicotine, flavoring agents, carbonyl compounds, and heavy metals. This review maps empirical evidence on CNS effects of e-cigarette exposure across biological model types. A systematic scoping review was conducted per the Arksey and O'Malley framework and reported per PRISMA-ScR guidelines. PubMed and Scopus were searched in January 2026 for studies from 2015 to 2026 examining quantifiable CNS outcomes following e-cigarette exposure in human, animal, or in vitro models. Data were extracted across eight domains and synthesized narratively. Seventy-four studies met inclusion criteria: 49 animal in vivo (66.2%), 17 human (23.0%), and 8 in vitro (10.8%), spanning 14 countries. Seven CNS outcome domains were identified: neuroinflammation and oxidative stress, blood-brain barrier (BBB) integrity, cognitive and behavioral outcomes, neuroimaging and pharmacokinetics, neurotransmitter systems and electrophysiology, developmental neurotoxicology, and other outcomes. Neuroinflammation and BBB disruption showed high directional consistency. Cognitive impairment, hippocampal volume reductions, and reward circuit reorganization were consistently observed. Developmental studies identified epigenomic reprogramming and disrupted GABAergic interneuron migration. Non-nicotine constituents were independently implicated in CNS toxicity. E-cigarette exposure is associated with a consistent and biologically plausible pattern of CNS harm. The developing brain represents a priority risk population given its heightened vulnerability to neurotoxic insult. Current evidence does not support the neurological safety of e-cigarettes; regulatory frameworks should mandate rigorous CNS-specific toxicity assessment for electronic nicotine delivery systems.

Keywords

• lektronik sigara
• merkezi sinir sistemi
• nörotoksisite
• nöroinflamasyon
• kapsam derlemesi

Supporting Institution

Bu araştırma, kamu, ticari veya kâr amacı gütmeyen sektörlerdeki herhangi bir fon kuruluşundan özel bir hibe almamıştır.

Ethical Statement

Yazar, bu çalışmanın araştırma ve yayın etiğine uygun olduğunu beyan eder. Çalışmada gerçekleştirilen tüm işlemler, ilgili kurumsal ve ulusal komitelerin etik standartlarına ve 1964 Helsinki Deklarasyonu ile sonraki değişikliklerine uygundur. Bu çalışma için etik onay gerekmemiştir. Yazarın beyan edilecek herhangi bir çıkar çatışması bulunmamaktadır.

Thanks

Akademik rehberlikleri, mentörlükleri ve hem kişisel hem de mesleki gelişimime kattıkları paha biçilmez katkılar için Dr. Cem Güler ve Prof. Dr. Nefise Ülkü Karabay Yavaşoğlu'na en derin şükranlarımı sunarım. Destekleri gerçek anlamda özel olmuştur. Koşulsuz sevgileri ve sürekli teşvikleriyle en büyük güç kaynağım olan anneme ve ablama da yürekten teşekkür ederim. Son olarak, bu süreçte yanımda olan sevgili arkadaşlarıma sonsuz destekleri, sabırları ve dostlukları için teşekkür ederim.

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