Article Text

Download PDFPDF
Dose–response effects of two nicotine salt formulations on electronic cigarette appeal and sensory attributes
  1. Dae-Hee Han1,2,
  2. Melissa Wong1,2,
  3. Natalia Peraza1,
  4. Erin A Vogel1,2,
  5. Rael Cahn2,3,
  6. Tyler B Mason1,2,
  7. Matthew Kirkpatrick1,2,
  8. Alayna P Tackett1,2,
  9. Adam M Leventhal1,2,4
  1. 1 Department of Population and Public Health Sciences, University of Southern California Keck School of Medicine, Los Angeles, California, USA
  2. 2 Institute for Addiction Science, University of Southern California, Los Angeles, California, USA
  3. 3 Department of Psychiatry and Behavioral Sciences, University of Southern California Keck School of Medicine, Los Angeles, California, USA
  4. 4 Department of Psychology, University of Southern California, Los Angeles, California, USA
  1. Correspondence to Dr Dae-Hee Han, University of Southern California Keck School of Medicine, Los Angeles, CA 90032, USA; daeheeha{at}


Objectives Various organic acids are used to create nicotine salt formulations, which may improve the appeal and sensory experience of vaping electronic cigarettes (e-cigarettes). This clinical experiment examined the effects of partially and highly protonated forms of two nicotine salt formulations (nicotine lactate and benzoate) versus free-base (no acid additive) on the appeal and sensory attributes of e-cigarettes.

Methods Current adult tobacco product users (n=116) participated in an online remote double-blind within-subject randomised experiment involving standardised self-administration of e-cigarette solutions varying in nicotine formulation (free-base, 50% nicotine lactate –1:2 lactic acid to nicotine molar ratio, 100% nicotine lactate – 1:1 ratio, 50% nicotine benzoate and 100% nicotine benzoate). Each formulation had equivalent nicotine concentrations (27.0–33.0 mg/mL) and was administered in four flavours in a pod-style device. After each administration, participants rated appeal (liking, disliking and willingness to use again) and sensory attributes (0–100 scale).

Results Compared with free-base nicotine, 50% and 100% nicotine lactate and benzoate yielded higher appeal, smoothness and sweetness and lower harshness and bitterness. Dose–response analyses found 100% vs 50% nicotine salt improved appeal, smoothness, bitterness and harshness for nicotine lactate and sweetness, smoothness and harshness for nicotine benzoate. Solutions with higher pH were associated with worse appeal and sensory attributes across nicotine formulations. Nicotine formulation effects did not differ by tobacco use status and flavours.

Conclusion Restricting benzoic acid or lactic acid additives or setting minimal pHs in e-cigarettes merits consideration in regulations designed to reduce vaping among populations deterred from using e-cigarettes with aversive sensory properties.

Trial registration number This study was registered under Identifier: NCT03742817 under the title ‘Effects of e-Cigarettes on Perceptions and Behavior’.

  • electronic nicotine delivery devices
  • nicotine
  • non-cigarette tobacco products
  • public policy

Data availability statement

Data are available on reasonable request.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Data availability statement

Data are available on reasonable request.

View Full Text


  • Contributors Conceptualisation: AML, APT, DH, EAV, MK, MW, NP, RC, TBM; data curation: DH, MW, NP; formal analysis: DH; original draft preparation: DH; review and editing: AML, APT, EAV, MK, MW, NP, RC, TBM; funding acquisition: AML; project administration: AML. DH is the guarantor who accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish. All authors read drafts, provided critical feedback and edits, and approved the entire article.

  • Funding This project was supported in part by the National Cancer Institute and the Food and Drug Administration Center for Tobacco Products (CTP) under Award Number U54CA180905, National Cancer Institute under award number R01CA229617 and National Institute on Drug Abuse under award number K24DA048160.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.