Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Grey matter morphometry in young adult e-cigarette users, tobacco cigarette users & non-using controls

Neuropsychopharmacology volume 50, pages 1455–1463 (2025)Cite this article

Subjects

Abstract

Despite the rise in electronic cigarette use in recent years, the neurobiological effects of daily e-cigarette use versus smoking cigarettes in young adults remains unknown. This study aimed to investigate the impact of regular, exclusive e-cigarette use on grey matter morphometry in young adults, age 18–25. Structural MRI data were collected from 3 distinct groups of participants (n = 78): daily, exclusive e-cigarette users; tobacco cigarette users; and non-using controls, to assess grey matter volume (GMV) differences. Voxel-based morphometry revealed significant GMV reductions in tobacco cigarette users in the left fusiform gyrus (FG), left and right inferior temporal gyrus (IFG), right middle temporal gyri, and right middle cingulate gyrus (MCG), compared to controls, as well as the anterior cingulate cortex (ACC), compared to both e-cigarette users and controls, even after adjusting for nicotine exposure history. Partial correlation analyses revealed that in tobacco cigarette users, GMV in the FG, ITG, MTG, and MCG displayed a strong, negative association with exposure history but not with nicotine dependence. GMV of the ACC was not associated with duration of use or nicotine dependence score, suggesting distinct relationships between ACC volume and smoking status and FG/ITG/MTG/MCG volume and smoking status. This indicates a distinct difference between regular tobacco cigarette and e-cigarette use, perhaps a relatively safer profile of e-cigarette use on GMV. These findings suggest that factors beyond nicotine, such as other toxicants in tobacco cigarette smoke, may contribute to the observed brain atrophy, or imply potential pre-existing vulnerabilities that might predispose individuals to take up smoking.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Section view from t-test images highlighting clusters with significant reductions in GMV in the CIG group.
Fig. 2: Partial correlation plots in CIG users of exposure history (controlling for Age of Initiation and Total Intracranial Volume) with GMV of regions of interest.

Similar content being viewed by others

Data availability

Data cannot be released because of privacy and ethics restrictions, but requests for access to de-identified patient-level data can be considered on reasonable request by contacting the corresponding author.

References

  1. Hammond D, Rynard VL, Reid JL. Changes in prevalence of vaping among youths in the United States, Canada, and England from 2017 to 2019. JAMA Pediatr. 2020;174:797–9.

    Article  PubMed Central  PubMed  Google Scholar 

  2. Government of Canada. Canadian Tobacco and Nicotine Survey (CTNS). Canada Stat. 2022;2021:1–5.

    Google Scholar 

  3. Kramarow EA, Elgaddal N. Current Electronic Cigarette Use Among Adults Aged 18 and Over: United States, 2021. NCHS Data Brief. 2023;475:1–8.

  4. Johnson JM, Muilenburg JL, Rathbun SL, Yu X, Naeher LP, Wang JS. Elevated Nicotine Dependence Scores among Electronic Cigarette Users at an Electronic Cigarette Convention. J Community Health. 2018;43:164–74.

    Article  PubMed  Google Scholar 

  5. Jankowski M, Krzystanek M, Zejda JE, Majek P, Lubanski J, Lawson JA, et al. E-cigarettes are more addictive than traditional cigarettes—A study in highly educated young people. Int J Environ Res Public Health. 2019;16:4–13.

    Article  Google Scholar 

  6. Chatterjee K, Alzghoul B, Innabi A, Meena N. Is vaping a gateway to smoking: A review of the longitudinal studies. Int J Adolesc Med Health. 2018;30:20160033.

  7. Siddiqui F, Mishu M, Marshall AM, Siddiqi K. E-cigarette use and subsequent smoking in adolescents and young adults: a perspective. Expert Rev Respir Med. 2019;13:403–5.

    Article  CAS  PubMed  Google Scholar 

  8. Breslau N, Peterson EL. Smoking cessation in young adults: Age at initiation of cigarette smoking and other suspected influences. Am J Public Health. 1996;86:214–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Ali FRM, Agaku IT, Sharapova SR, Reimels EA, Homa DM. Onset of regular smoking before age 21 and subsequent nicotine dependence and cessation behavior among US adult smokers. Prev Chronic Dis. 2020;17:1–6.

    Article  Google Scholar 

  10. Squeglia LM, Gray KM. Alcohol and Drug Use and the Developing Brain. Curr Psychiatry Rep. 2016;18. https://doi.org/10.1007/s11920-016-0689-y.

  11. Arain M, Haque M, Johal L, Mathur P, Nel W, Rais A, et al. Maturation of the adolescent brain. Neuropsychiatr Dis Treat. 2013;9:449–61.

    PubMed Central  PubMed  Google Scholar 

  12. Peng P, Li M, Liu H, Tian YR, Chu SL, van Halm-Lutterodt N, et al. Brain structure alterations in respect to tobacco consumption and nicotine dependence: a comparative voxel-based morphometry study. Front Neuroanat. 2018;12. https://doi.org/10.3389/fnana.2018.00043.

  13. Gallinat J, Meisenzahl E, Jacobsen LK, Kalus P, Bierbrauer J, Kienast T, et al. Smoking and structural brain deficits: A volumetric MR investigation. Eur J Neurosci. 2006;24:1744–50.

    Article  PubMed  Google Scholar 

  14. Stoeckel LE, Chai XJ, Zhang J, Whitfield-Gabrieli S, Evins AE. Lower gray matter density and functional connectivity in the anterior insula in smokers compared with never smokers. Addiction Biol. 2016;21:972–81.

    Article  Google Scholar 

  15. Chen Y, Chaudhary S, Wang W, Li CSR. Gray matter volumes of the insula and anterior cingulate cortex and their dysfunctional roles in cigarette smoking. Addiction Neurosci. 2022;1:100003.

  16. Liao Y, Tang J, Liu T, Chen X, Hao W. Differences between smokers and non-smokers in regional gray matter volumes: A voxel-based morphometry study. Addiction Biology. 2012;17:977–80.

    Article  PubMed  Google Scholar 

  17. Brody AL, Mandelkern MA, Jarvik ME, Lee GS, Smith EC, Huang JC, et al. Differences between smokers and nonsmokers in regional gray matter volumes and densities. Biol Psychiatry. 2004;55:77–84.

    Article  PubMed  Google Scholar 

  18. Zhang X, Salmeron BJ, Ross TJ, Geng X, Yang Y, Stein EA. Factors underlying prefrontal and insula structural alterations in smokers. Neuroimage. 2011;54:42–48.

    Article  PubMed  Google Scholar 

  19. Fritz HC, Wittfeld K, Schmidt CO, Domin M, Grabe HJ, Hegenscheid K, et al. Current smoking and reduced gray matter volume - A voxel-based morphometry study. Neuropsychopharmacology. 2014;39:2594–2600.

    Article  PubMed Central  PubMed  Google Scholar 

  20. Marques P, Piqueras L, Sanz MJ. An updated overview of e-cigarette impact on human health. Respir Res. 2021;22:1–14.

    Article  Google Scholar 

  21. Goniewicz ML, Smith DM, Edwards KC, Blount BC, Caldwell KL, Feng J, et al. Comparison of Nicotine and Toxicant Exposure in Users of Electronic Cigarettes and Combustible Cigarettes. JAMA Netw Open. 2018;1:1–16.

    Article  Google Scholar 

  22. Caliri AW, Tommasi S, Besaratinia A. Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer. Mutat Res Rev Mutat Res. 2021;787:108365.

    Article  CAS  PubMed  Google Scholar 

  23. Durazzo TC, Meyerhoff DJ, Nixon SJ. Chronic Cigarette Smoking: Implications for Neurocognition and Brain Neurobiology. Int J Environ Res Public Health. 2010;7:3760–91.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Heatherton TF, Kozlowski LT, Frecker RC, Fagerstrom K. The Fagerström Test for Nicotine Dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict. 1991;86:1119–27.

    Article  CAS  PubMed  Google Scholar 

  25. Rahman A, Mohamed MN, Jamshed S, Mahmood S, Baig MI. The development and assessment of modified Fagerstrom test for nicotine dependence scale among Malaysian single electronic cigarette users. J Pharm Bioallied Sci. 2020;12:671.

    Article  Google Scholar 

  26. Rolls ET, Huang C-C, Lin C-P, Feng J, Joliot M. Automated anatomical labelling atlas 3. Neuroimage. 2020;206:116189.

    Article  PubMed  Google Scholar 

  27. Thomas Yeo BT, Krienen FM, Sepulcre J, Sabuncu MR, Lashkari D, Hollinshead M, et al. The organization of the human cerebral cortex estimated by intrinsic functional connectivity. J Neurophysiol. 2011;106:1125–65.

    Article  PubMed Central  Google Scholar 

  28. Saunders JB, Aasland OG, Babor TF, De La Fuente JR, Grant M. Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption‐II. Addiction. 1993;88:791–804.

    Article  CAS  PubMed  Google Scholar 

  29. Kunas SL, Hilbert K, Yang Y, Richter J, Hamm A, Wittmann A, et al. The modulating impact of cigarette smoking on brain structure in panic disorder: A voxel-based morphometry study. Soc Cogn Affect Neurosci. 2020;15:849–59.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Durazzo TC, Insel PS, Weiner MW. Greater regional brain atrophy rate in healthy elderly subjects with a history of cigarette smoking. Alzheimers Dementia. 2012;8:513–9.

    Article  Google Scholar 

  31. Weidler C, Gramegna C, Müller D, Schrickel M, Habel U. Resting-state functional connectivity and structural differences between smokers and healthy non-smokers. Sci Rep. 2024;14:6878.

  32. Cabeza R, Nyberg L. Imaging cognition II: An empirical review of 275 PET and fMRI studies. J Cogn Neurosci. 2000;12:1–47.

    Article  CAS  PubMed  Google Scholar 

  33. Tranel D, Damasio H, Damasio AR. A neural basis for the retrieval of conceptual knowledge. Neuropsychologia. 1997;35:1319–27.

    Article  CAS  PubMed  Google Scholar 

  34. Chao LL, Haxby JV, Martin A. Attribute-based neural substrates in temporal cortex for perceiving and knowing about objects. Nat Neurosci. 1999;2:913–9.

    Article  CAS  PubMed  Google Scholar 

  35. Ishai A, Ungerleider LG, Martin A, Schouten JL, Haxby JV. Distributed representation of objects in the human ventral visual pathway. Proc Natl Acad Sci USA. 1999;96:9379–84.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Herath P, Kinomura S, Roland PE. Visual recognition: Evidence for two distinctive mechanisms from a PET study. Hum Brain Mapp. 2001;12:110–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Mesulam MM. From sensation to cognition. Brain. 1998;121:1013–52.

    Article  PubMed  Google Scholar 

  38. Sergent J, Ohta S, Macdonald B. Functional Neuroanatomy of Face and Object Processing. Brain. 1992;115:15–36.

    Article  PubMed  Google Scholar 

  39. Wang X, Han Z, He Y, Caramazza A, Song L, Bi Y. Where color rests: Spontaneous brain activity of bilateral fusiform and lingual regions predicts object color knowledge performance. Neuroimage. 2013;76:252–63.

    Article  PubMed  Google Scholar 

  40. Weiner KS, Golarai G, Caspers J, Chuapoco MR, Mohlberg H, Zilles K, et al. The mid-fusiform sulcus: A landmark identifying both cytoarchitectonic and functional divisions of human ventral temporal cortex. Neuroimage. 2014;84:453–65.

    Article  PubMed  Google Scholar 

  41. Kanwisher N, McDermott J, Chun MM. The fusiform face area: A module in human extrastriate cortex specialized for face perception. J Neurosci. 1997;17:4302–11.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Wilson SJ, Sayette MA, Delgado MR, Fiez JA. Instructed smoking expectancy modulates cue-elicited neural activity: A preliminary study. Nicotine Tobacco Res. 2005;7:637–45.

    Article  Google Scholar 

  43. Due DL, Huettel SA, Hall WG, Rubin DC. Activation in mesolimbic and visuospatial neural circuits elicited by smoking cues: Evidence from functional magnetic resonance imaging. Am J Psychiatry. 2002;159:954–60.

    Article  PubMed  Google Scholar 

  44. David S, Munafò M, Johansen-Berg H. Ventral striatum-nucleus accumbens activation to smoking-related pictorial cues in smokers and nonsmokers - fMRI. Soc Biological Psychiatry. 2005;58:488–94.

    Article  Google Scholar 

  45. Zeng F, Hong W, Zha R, Li Y, Jin C, Liu Y, et al. Smoking related attention alteration in chronic obstructive pulmonary disease-smoking comorbidity. BMC Pulm Med. 2022;22:1–11.

    Article  Google Scholar 

  46. Xue T, Dong F, Huang R, Tao Z, Tang J, Cheng Y, et al. Dynamic Neuroimaging Biomarkers of Smoking in Young Smokers. Front Psychiatry. 2020;11:663.

  47. Goldstein RZ, Volkow ND. Drug addiction and its underlying neurobiological basis: Neuroimaging evidence for the involvement of the frontal cortex. Am J Psychiatry. 2002;159:1642–52.

    Article  PubMed Central  PubMed  Google Scholar 

  48. Janes AC, Farmer S, Peechatka AL, Frederick BDB, Lukas SE. Insula-dorsal anterior cingulate cortex coupling is associated with enhanced brain reactivity to smoking cues. Neuropsychopharmacology. 2015;40:1561–8.

    Article  PubMed Central  PubMed  Google Scholar 

  49. Lerman C, Gu H, Loughead J, Ruparel K, Yang Y, Stein EA. Large-scale brain network coupling predicts acute nicotine abstinence effects on craving and cognitive function. JAMA Psychiatry. 2014;71:523–30.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Engelmann JM, Versace F, Robinson JD, Minnix JA, Lam CY, Cui Y, et al. Neural substrates of smoking cue reactivity: A meta-analysis of fMRI studies. Neuroimage. 2012;60:252–62.

    Article  PubMed  Google Scholar 

  51. Wilson SJ, Sayette MA, Fiez JA. Prefrontal responses to drug cues: A neurocognitive analysis. Nat Neurosci. 2004;7:211–4.

    Article  PubMed Central  PubMed  Google Scholar 

  52. Lin X, Deng J, Shi L, Wang Q, Li P, Li H, et al. Neural substrates of smoking and reward cue reactivity in smokers: a meta-analysis of fMRI studies. Transl Psychiatry. 2020;10:97.

  53. Allenby C, Falcone M, Wileyto EP, Cao W, Bernardo L, Ashare RL, et al. Neural cue reactivity during acute abstinence predicts short-term smoking relapse. Addiction Biol. 2020;25:1–9.

    Article  Google Scholar 

  54. Chen WJA, Edwards RB, Romero RD, Parnell SE, Monk RJ. Long-term nicotine exposure reduces Purkinje cell number in the adult rat cerebellar vermis. Neurotoxicol Teratol. 2003;25:329–34.

    Article  CAS  PubMed  Google Scholar 

  55. Dwyer JB, McQuown SC, Leslie FM. The dynamic effects of nicotine on the developing brain. Pharmacol Ther. 2009;122:125–39.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Trauth JA, Seidler FJ, Slotkin TA. An animal model of adolescent nicotine exposure: Effects on gene expression and macromolecular constituents in rat brain regions. Brain Res. 2000;867:29–39.

    Article  CAS  PubMed  Google Scholar 

  57. Akyol S, Erdogan S, Idiz N, Celik S, Kaya M, Ucar F, et al. The role of reactive oxygen species and oxidative stress in carbon monoxide toxicity: An in-depth analysis. Redox Report. 2014;19:180–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Hassan W, Noreen H, Rehman S, Kamal MA, da Rocha JBT. Association of Oxidative Stress with Neurological Disorders. Curr Neuropharmacol. 2021;20:1046–72.

    Article  Google Scholar 

  59. Shen Z, Huang P, Qian W, Wang C, Yu H, Yang Y, et al. Severity of dependence modulates smokers’ functional connectivity in the reward circuit: a preliminary study. Psychopharmacology. 2016;233:2129–37.

    Article  CAS  PubMed  Google Scholar 

  60. Megías-Robles A, Cándido A, Maldonado A, Baltruschat S, Catena A. Differences between risk perception and risk-taking are related to impulsivity levels. Int J Clin Health Psychol. 2022;22:100318.

  61. Kozak K, Lucatch AM, Lowe DJE, Balodis IM, MacKillop J, George TP. The neurobiology of impulsivity and substance use disorders: implications for treatment. Ann N Y Acad Sci. 2019;1451:71–91.

    Article  PubMed  Google Scholar 

  62. Manzione LC, Shan L, Azagba S. Associations Between Risk Perceptions and Cigarette, E-cigarette, and Dual-Product Use Among Canadian Adolescents. Tob Use Insights. 2020;13:1179173X2090378.

    Article  Google Scholar 

  63. Government of Canada. Summary of results for the Canadian Student Tobacco, Alcohol and Drugs Survey 2018-19. Canada Statistics. 2019.

Download references

Funding

Kanwar Boparai is supported by funds from the Centre for Addiction and Mental Health, and The University of Toronto. Research was supported by grants to Laurie Zawertailo: Pfizer GRAND grant (WS2391913), CCS grant (707321-1) and CAMH Womenmind (1001079).

Author information

Authors and Affiliations

  1. INTREPID Lab, IMHPR, Centre for Addiction and Mental Health, 1025 Queen Street West, Toronto, ON, M6J 1H4, Canada

    Kanwar Boparai, Peter Selby & Laurie Zawertailo

  2. Department of Pharmacology and Toxicology, Temerty Faculty of Medicine, University of Toronto, Medical Sciences Building, Room 4207, 1 King’s College Circle, Toronto, ON, M5S 1A8, Canada

    Kanwar Boparai & Laurie Zawertailo

  3. Azrieli Adult Neurodevelopmental Centre, Centre for Addiction and Mental Health, 1025 Queen Street West, Toronto, ON, M6J 1H4, Canada

    Hsiang-Yuan Lin

  4. Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, 250 College Street, Toronto, ON, M5T 1R8, Canada

    Hsiang-Yuan Lin & Peter Selby

  5. Dalla Lana School of Public Health, University of Toronto, 155 College Street, Toronto, ON, M5T 1M7, Canada

    Peter Selby

  6. Department of Family and Community Medicine, Temerty Faculty of Medicine, University of Toronto, 500 University Ave, Toronto, ON, M5G 1V7, Canada

    Peter Selby

Authors
  1. Kanwar Boparai
    View author publications

    Search author on:PubMed Google Scholar

  2. Hsiang-Yuan Lin
    View author publications

    Search author on:PubMed Google Scholar

  3. Peter Selby
    View author publications

    Search author on:PubMed Google Scholar

  4. Laurie Zawertailo
    View author publications

    Search author on:PubMed Google Scholar

Contributions

Kanwar Boparai (Investigation, Formal analysis, Methodology, Writing—original draft, Writing—review & editing), Hsiang-Yuan Lin (Methodology, Writing—review & editing), Peter Selby (Conceptualization, Funding acquisition, Resources, Writing—review & editing), and Laurie Zawertailo (Conceptualization, Methodology, Funding acquisition, Resources, Supervision, Writing—review & editing).

Corresponding author

Correspondence to Laurie Zawertailo.

Ethics declarations

Competing interests

KB, HL and LZ have no competing interests to declare. PS holds the Vice-Chair, Research and Giblon Professor in Family Medicine Research, a university named Professorship at the University of Toronto.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Boparai, K., Lin, HY., Selby, P. et al. Grey matter morphometry in young adult e-cigarette users, tobacco cigarette users & non-using controls. Neuropsychopharmacol. 50, 1455–1463 (2025). https://doi.org/10.1038/s41386-025-02086-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41386-025-02086-3

Search

Advanced search

Quick links