Study design and questionnaires

Clinical data were collected during January and September 2020. Two appointments were scheduled for the test subjects to participate in the study. The first appointment was considered a screening, whereas the actual measurement took place at the second appointment. Usual smoking or e-cigarette consumption behavior was enquired with standardized and specially designed questionnaires.

An initial questionnaire at the screening appointment served on the one hand to assess sociodemographic data such as sex, age, weight and known pre-existing illnesses and on the other hand to assess smoking and e-cigarette consumption behavior. For example, the frequency of smoking or vaping and preferred manufacturers were assessed. At the screening appointment, physical dependence on nicotine was assessed with the Fagerström Test of Nicotine Dependence (FTND) according to Heatherton et al.³⁴. No validated version of the FTND exists for e-cigarette consumption. Thus, instead of the FTND, an adapted but unvalidated questionnaire for e-cigarettes was used for participants in the JUUL study arms. The Questionnaire on Smoking Urges (QSU-G) in the German version by Müller et al. was used to assess craving³⁵. QSU-G was assessed before and immediately after the vaping/smoking sessions. Further details on QSU-G and its evaluation are given in the ^{Supplementary Information}. Immediately after vaping, participants rated negative effects (side effects) of the e-cigarette on a visual analog scale (VAS) ranging from 0 (no effect) to 10 (strongest effect). The VAS used in this study was based on the one used in previous studies on e-cigarettes^36,37 and enquired urge to vomit, nausea, perspiration, headaches, palpitations, cold hands or feet, salivation, dizziness, irritation of the throat or mouth, and lightheadedness.

E-cigarettes were weighed (MC 1, Sartorius, Göttingen, Germany) before and after the measurement to determine the liquid consumption. Nicotine doses were calculated by considering liquid density (1.16 g/cm³) and the measured nicotine concentration in the respective e-liquid (17.69 mg/mL for “modified” JUUL and 17.20 mg/mL for “initial” JUUL)³².