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 conducting high impact studies to develop interventions to reduce the burden of tobacco use in people with SUDs.

PROJECT NARRATIVE The majority of individuals with opioid use disorder (OUD) smoke cigarettes, and they have less success quitting smoking and higher rates of tobacco-related mortality compared to the general smoking population. Novel cigarette reduction approaches, such as substitution of electronic cigarettes (e-cigarettes) for combusted cigarettes, are urgently needed in this population. This proposal will employ a randomized waitlist-controlled trial with a mixed-methods sequential explanatory design to investigate the feasibility, acceptability, and preliminary effects of substituting e-cigarettes for cigarettes on tobacco use and exposure (e.g., cigarettes smoked per day, biomarkers, cigarette dependence) in individuals who smoke (not ready to quit smoking) receiving OUD treatment, to help inform tobacco control policy and clinical practice.