ABSTRACT/PROJECT SUMMARY Tobacco use is a leading cause of preventable mortality for people receiving medication treatment for opioid use disorder (MOUD). Individuals receiving MOUD have a five-fold higher prevalence of tobacco smoking and substantially lower quit rates than the general population, even when using existing treatments such as FDA- approved pharmacotherapies. Electronic cigarettes (e-cigarettes), if substituted for combusted cigarette smoking, may offer a harm reduction strategy for individuals receiving MOUD who smoke (MOUD-TUD) who are not ready to quit smoking. Little work has been done to test this approach in MOUD-TUD. Addressing this knowledge gap has the potential to answer a critical question of whether e-cigarettes can reduce tobacco use and exposure in this highly vulnerable smoker population. It can also inform clinical practice and policymaking decisions. In this 3-year career development award, I propose to conduct a pilot randomized waitlist-controlled trial to assess the feasibility, acceptability, and preliminary effects of substituting the NIDA standardized research e-cigarette (SREC) for combusted cigarettes in MOUD-TUD who are not ready to quit smoking. A waitlist controlled RCT using a mixed-methods sequential explanatory design will investigate the impact of SREC provision on: 1) tobacco use behavior (e.g., cigarettes per day [primary outcome], SREC use), 2) biomarkers (e.g., carbon monoxide, anabasine), 3) cigarette dependence and withdrawal, and 4) short-term health effects and tolerability (e.g., respiratory symptoms, substance use). In the proposed RCT, N=40 adults stable on MOUD with buprenorphine who report daily smoking recruited from MGH primary care practices will be randomly assigned to receive the SREC for 8 weeks, either immediately (iSREC), or after an 8-week delay (waitlist control [WLC]). They will be followed an additional 4 weeks after SREC provision ends (to 12 weeks in iSREC and 20 weeks in WLC). Each scientific aim corresponds to a specific training goal in three competency domains: 1) design and conduct of clinical trials, 2) longitudinal quantitative data analysis and, 3) qualitative and mixed-methods research. The scientific and training aims will be executed with mentorship from Drs. Nancy Rigotti and Eden Evins (co-primary mentors), Dr. Elyse Park (co-mentor), and a team of expert advisors. The training plan for this career development award leverages mentorship from a team of internationally recognized leaders in patient-oriented tobacco, e-cigarette, and OUD research, as well as rigorous coursework taught by renowned Harvard faculty. I will acquire both the skillset and the feasibility data needed to support a fully powered R01 proposal to conduct a RCT testing a smoking intervention to reduce the burden of smoking in those with OUD. The proposed study, in addition to completion of my training goals, will launch me towards my long-term goal of a career as an independent investigator c...