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Effectiveness of Non-Nicotinic E-Cigarettes to Reduce Cue- and Abstinence-Induced Cigarette Craving in Non-Treatment Seeking Daily Dependent Smokers

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Electronic cigarettes (e-cigarettes) are potential tools for smoking cessation because they deliver nicotine and simulate smoking behaviors. The contribution of sensorimotor versus pharmacological substitution is unknown.


To evaluate whether non-nicotinic e-cigarettes, used alone or with nicotine lozenges, can attenuate cigarette craving following visual cue presentation or acute (3 h post ad-lib use) abstinence in dependent daily smokers.


Following overnight (12 hours) abstinence, 41 daily smokers were exposed to 4 experimental conditions on separate days: (i) tobacco cigarettes (CIG); (ii) non-nicotinic e-cigarettes with placebo lozenges (EPL); (iii) non-nicotinic e-cigarettes with 4 mg nicotine lozenge (ENL); and (iv) 4 mg nicotine lozenge (NL). Cigarette craving was assessed following presentation of neutral and smoking cues at various time points using the Brief Questionnaire of Smoking Urges (QSU-B) and visual analog scales (VAS).


All experimental conditions significantly reduced participants’ baseline overnight abstinence cigarette craving. ENLs and NLs attenuated smoking-cue-induced cravings to a greater extent than CIGs, where cravings were significantly higher with CIGs compared to ENLs [mean difference (MD) ± standard error (SE) in QSU-B = 3.2 ± 0.84, P = 0.002; VAS = 12.7 ± 2.7, P < 0.0005] and NLs [MD ± SE in QSU-B = 2.7 ± 0.92, P = 0.031; VAS = 8.1 ± 2.3, P = 0.005]. Craving responses to cues after 3 h were higher after smoking CIGs compared to ENLs [MD ± SE in QSU-B = 3.9 ± 1.4, P = 0.047; VAS = 14.1 ± 3.6, P = 0.002] and NLs [MD ± SE in QSU-B = 3.2 ± 1.1, P = 0.046; VAS = 9.7 ± 3.1, P = 0.017].


Behavioral simulation of smoking with or without nicotine reduces nicotine craving. Compared to cigarettes, ENL with NL or NL alone attenuates cigarette craving over time. Future clinical trials should evaluate the combination of ENL and NL as a method for smoking reduction or cessation.

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PS receives a stipend from CAMH as a Senior Medical Consultant and Clinician Scientist. He also receives a stipend from the Department of Family and Community Medicine as a Clinician Scientist. LZ is a paid employee of the Centre for Addiction and Mental Health. GN is a graduate trainee and SA is a post-doctoral fellow. This study received funding support from the Ontario Ministry of Health Services Research Fund Grant #409. Funding for infrastructure was from the Centre for Addiction and Mental Health.

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Authors and Affiliations



LZ, PS, and GN conceived of and designed the experiments. GN performed the experiments and gathered the data. GN and SA analyzed the data. GN wrote the initial drafts of the paper. All authors contributed to subsequent drafts and have approved the final version.

Corresponding author

Correspondence to Laurie Zawertailo.

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None of the funding sources participated in the execution of the project, generation of results, interpretation of the data, nor drafting of the manuscript.

Conflict of interest

PS reports receiving grants and/or salary and/or research support from the Centre for Addiction and Mental Health; Health Canada; Ontario Ministry of Health and Long-term care; Canadian Institutes of Health Research; Canadian Centre on Substance Use and Addiction; Public Health Agency of Canada; Ontario Lung Association; Medical Psychiatry Alliance; Extensions for Community Healthcare Outcomes; Canadian Cancer Society Research Institute; Cancer Care Ontario; Ontario Institute for Cancer Research; Ontario Brain Institute; McLaughlin Centre; Academic Health Sciences Centre; Workplace Safety and Insurance Board; National Institutes of Health; and the Association of Faculties of Medicine of Canada. PS also reports receiving funding and/or honoraria from the following commercial organizations: Pfizer Inc./Canada, Shoppers Drug Mart, Bhasin Consulting Fund Inc., Patient-Centered Outcomes Research Institute, ABBVie, and Bristol-Myers Squibb. Further, PS reports receiving consulting fees from Pfizer Inc./Canada, Evidera Inc., Johnson & Johnson Group of Companies, Medcan Clinic, Inflexxion Inc., V-CC Systems Inc., MedPlan Communications, Kataka Medical Communications, Miller Medical Communications, Nvision Insight Group, and Sun Life Financial. LZ has received peer-reviewed funding from Canadian Institutes of Health Research, Canadian Cancer Society, and Ontario Ministry of Health of Long-term Care, including salary support from Pfizer Inc. (GRAND Award) and the Health Services Research Fund from the Ontario Ministry of Health. All other authors declare no conflict of interest.

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Ng, G., Attwells, S., Selby, P. et al. Effectiveness of Non-Nicotinic E-Cigarettes to Reduce Cue- and Abstinence-Induced Cigarette Craving in Non-Treatment Seeking Daily Dependent Smokers. Psychopharmacology 238, 1461–1472 (2021).

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