PROJECT SUMMARY Despite increasing use of electronic cigarettes (ECs) in the population, little is known about gender differences in the potential risks and benefits associated with e-cig use in current combustible cigarette (CC) smokers. To help address questions like this, NIDA commissioned the development of a Standard Research E- Cigarette (SREC) and a 2-year FOA (PAR-18-220) to encourage its evaluation. Much evidence suggests that male and female CC smokers differ in terms of nicotine consumption, reinforcement, withdrawal severity, and quit rate. However, it is largely unknown whether there are gender differences in these factors as result of EC use. Pursuant to this FOA, the objective of this proposal is to characterize potential gender differences when switching to nicotine and placebo SRECs from CCs on product use, product acceptability, reinforcement, and nicotine dependence symptoms among adult daily CC smokers. Participants (n=140) will be 70 male and 70 female adult daily CC smokers who are currently uninterested in quitting smoking but who are interested in trying ECs. Participants will smoke their usual brand (UB) CC products during Phase 1 (Baseline; weeks 1-2) and will be instructed to use the SREC (either nicotine [15 mg/mL; SREC-NIC] or placebo [0 mg/mL; SREC- PLA]), during Phases 2 (weeks 3-4) and 3 (weeks 5-6) whenever they have the urge to smoke. Our aims will be to characterize: (1) The effects of switching to nicotine vs. placebo SRECs from CCs on product use, product acceptability, reinforcement, and nicotine dependence symptoms among adult daily CC smokers; (2) the differences between male and female CC smokers when switching to nicotine vs. placebo SRECs from CCs on product use, product acceptability, reinforcement, and nicotine dependence symptoms; and (3) which factors moderate or mediate the effects of switching to nicotine and placebo SRECs from CCs among male and female CC smokers. This project is significant because it will examine the impact of SREC use separately for men and women, who are known to respond to nicotine products differently, and provide NIDA with information about potential gender differences in the ability of CC users to switch to SRECs, in the reinforcing effects of SRECs compared to CCs, and in dual/poly use of SRECs and CCs. This proposal is innovative because it will characterize the potential differences of switching to SRECs from CCs between men and women using a controlled clinical trial design. The positive impact of this study will be to provide scientific information on whether a standardized research e-cig is found to be used and accepted by both men and women CC smokers, which would indicate whether it could serve as a good model of future e-cig research.