Design and Objective: The primary goal of this research is to assess the ability of alternative products (VLNCs vs. e-cigs vs. no alternative product; between-subjects factor) to serve as a substitute for conventional cigarettes and how this is influenced by steady-state nicotine (nicotine vs. placebo patches; within-subjects factor). In addition, the investigators will explore the contexts in which participants are and are not able to switch from their conventional cigarettes. Such contextual information will provide insight into internal (i.e., withdrawal, expectancies) and external environments (i.e., being around smokers, smoking restrictions) that promote or interfere with switching behavior. The investigators will also explore person factors and beliefs that may drive alternative product use and substitution success. Person factors that may influence use behavior include sex (a key biological variable), education level, dependence, instrumental smoking motives (e.g., smoking for affect regulation, taste, or social experiences), and psychiatric comorbidity. Beliefs that may influence use behavior include beliefs about the safety and addiction potential of conventional cigarettes and the alternative products. Understanding the relation of person factors and beliefs with use behavior could inform regulatory actions related to product labeling and education. Finally, the investigators will explore potential mechanisms that might drive use behavior and support substitution.

This research will enroll 180 adult smokers in a mixed design study with a within-subjects factor (active nicotine patch vs. placebo patch) and a between-subjects factor (alternative products: VLNCs, e-cigs, or no product). Participants will be randomized to receive either 4 weeks of VLNCs, 4 weeks of e-cigs, or no alternative product. After one week practicing with the alternative product, participants will complete the first of two 7-day switching trials during which they will be asked to refrain from smoking their own cigarettes and encouraged to use the alternative product to which they have been assigned (although the no alternative product group will not have any other products to use). All participants will be given patches (active nicotine or placebo, in counterbalanced order) to use during the Switch Week. After this first Switch Week, participants will smoke normally for one week and then have their second Switch Week using the other type of patch (active or placebo). Participants will complete Ecological Momentary Assessments (EMAs) on smartphones at baseline and during the 4 weeks of product use. EMA targets include own cigarette use, alternative product use, withdrawal symptoms, rewarding value of product use (e.g., taste, buzz), and environmental and affective context of any tobacco product use. The investigators will then conduct a 3-month follow-up to assess cigarette and e-cig use, risk perceptions, and future use intentions.

This design addresses the six critical methodological issues for understanding the impact of alternative products outlined by Villanti et al.: 1) rigorous assessment of the key outcome (conventional cigarettes smoked); 2) assessment of product use during switching; 3) use of appropriate control/comparison groups; 4) measurement of product exposure/use that precedes switching; 5) evaluation of the dose and duration of product exposure/use; and 6) clear evaluation of the type and quality of the products used (e.g., satisfaction).

Recruitment and Participants: Participants from the greater Madison and Milwaukee, Wisconsin areas will be recruited via media recruitment methods (i.e., television, newspaper, and earned media) that have recruited thousands of smokers. Investigators will also use Internet/Facebook advertisements that have been successful in recent e-cig studies that recruited 422 smokers willing to provide EMA data during seven 2-week assessment periods over 2 years and 74 dual users willing to reduce combustible cigarette use and switch to using only e-cigs. Given this, it is feasible to recruit 180 smokers for this study within 18 months.

Procedures and Measures: Interested smokers will complete a phone screen to determine initial eligibility. Potentially eligible smokers will attend an orientation visit where, after providing a breath sample to verify eligibility (CO \> 6 ppm), they will receive a detailed description of the study and provide written informed consent, and complete baseline assessments. At Visit 1, participants will be randomized to receive VLNCs, e-cigs, or no alternative product and will be trained to use the product. The study database will randomize participants, stratified by clinic, gender, and race \[White vs. Non-White\], to enhance scientific rigor and reproducibility. Participants will be trained to use the smartphone to complete daily assessments, using the training that was effective in prior research, and will schedule future study visits. Participants will use their alternative products as they would like for one week to become comfortable with the product. At Visit 2, participants will complete assessments, provide a breath sample for CO assessment and a urine sample for cotinine assessment, receive feedback on their compliance with the smartphone assessments, and be given study patches to use during Switch Week 1 when they will be asked to abstain from using their own cigarettes for the week. Participants will then attend a mid-Switch Week visit (Visit 3) and an end-of-Switch Week visit (Visit 4) to assess biomarkers (a breath sample for CO assessment and a urine sample for cotinine). At Visit 4, the end of Switch Week 1, participants will be told that they can smoke as usual for a week. Then, at the start of Switch Week 2 (Visit 5), participants will be given the other type of patch (active or placebo) and asked to abstain from smoking their own cigarettes for a week. As during the prior Switch Week, participants will attend visits mid-week and at the end of the week to assess biomarkers (Visits 6 and 7). The investigators will attempt to schedule appointments at the same time of day (i.e., within a 2-hour window) for each participant so that there is consistent time for product use prior to providing the biological samples across study visits. Participants will complete a follow-up assessment call at 3 months. The baseline visit will last 2 hours, but subsequent visits will last \<30 minutes. Participants will carry a smartphone to complete EMAs from Orientation through all 4 weeks of product use.

Knowledge to be Gained: The results from this research will provide important insight into how well very low nicotine cigarettes and e-cigarettes serve as a substitute for conventional cigarettes and how this is influenced by the presence of steady-state nicotine. Further, these data will inform scientists and regulators about the potential mechanisms that may support the use of alternative products. This information will aid scientists and regulatory bodies in understanding the real-world impact of potential regulatory policies regarding access to safer nicotine sources and reducing the addiction potential of combustible tobacco products.