Double-blind (for the two active arms), randomized, three-arm (two active and one control) clinical trial investigating factors (e.g. nicotine concentration) influencing the success of smoking cessation strategies and possible health risks related to nicotine salt vaping.

At the clinic screening visit demographics, smoking (including the Fagerström Test for Cigarette Dependence (FTCD) Questionnaire) and medical history, concomitant medication, vital signs, body mass index (BMI) and exhaled carbon monoxide (CO) will be assessed, and a physical examination will be performed. Saliva samples will be collected for cotinine and nicotine metabolite ratio (NMR) measurement, urine samples for urinary anabasine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), nicotine metabolites, tobacco-specific nitrosamines (TSNA), and VOC, and blood samples for genotyping, steroid levels, blood lipids, creatinine, and glucose.

After randomization the open system vape device and the nicotine salt e-liquids will be distributed to the participants of the two active arms. Use of e-liquids in the active arms will be ad libitum during three months and will be monitored by returned empty e-liquid bottles.

All groups will receive smoking cessation counseling at baseline, week 1, and week 4. Visits at the center at baseline, week 4, and 3 months will include questionnaires regarding TC and EC use, respiratory symptoms, liking, and adverse events, measurement of heart rate, blood pressure, BMI, blood steroid levels, HDL, LDL, creatinine and glucose, and measurement of urinary TSNA, VOC and nicotine metabolites. For participants self-reporting TC abstinence, exhaled CO validation and urinary anabasine and NNAL will be collected to verify tobacco abstinence.

A follow-up visit also assessing TC abstinence will take place at 6 months.

Inclusion Criteria:

• Adult (≥ 18 years old) smokers (at least 5 TC per day for at least 12 months)
• Motivated to quit smoking as evidenced by signing the informed consent form at trial enrolment specifying that a target quit date will be set
• Exhaled CO ≥ 10 ppm or saliva cotinine of > 30 ng/ml (in case of borderline CO measurement of 6-10 ppm) at screening
• Willing to participate in the trial even if allocated to the control group
• Ability to communicate well with the investigator and to understand and comply with the requirements of the study
• Signed informed consent form

Exclusion Criteria:

• Known hypersensitivity/allergy to a content of the e-liquid
• Pregnancy or breast feeding
• Intention to become pregnant during the course of the study
• Current regular use of EC or tobacco heating systems
• Use of NRT, varenicline, or bupropion in the month prior to the screening visit
• People who smoke tobacco combined with marijuana and do not currently want to quit marijuana use
• Participation in an interventional trial within 30 days prior to the screening visit
• Legal incapacity or limited legal capacity at screening
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol

Data that relates to individual, primary publications (and not the whole study database as such) will be deposited in the Bern Open Repository and Information System (BORIS). All efforts will be made to protect privacy and to de-identify the data. Data will be shared on request under the following conditions: A meaningful study question by the requester, outline of the planned analyses, valid methodology, signed data sharing agreement that contains a confidentiality agreement in case of sensitive data.