Project Summary Despite the importance of smoking withdrawal symptoms (e.g., craving, negative affect, disrupted cognition) for understanding tobacco/nicotine dependence and elucidating intervention targets, the parent study is the first-ever prospective, controlled comparison of abstinence-induced withdrawal between people who use electronic nicotine delivery systems (ENDS) and those who smoke cigarettes. However, like most research in the field, we currently exclude people with schizophrenia (SCZ). Lack of representation of people with SCZ is a major problem in nicotine/tobacco research, contributing to greater tobacco-related health disparities than perhaps any other population segment, with extremely high rates of use and low rates of cessation, which contributes to a marked excess in morbidity and mortality. A burgeoning literature is examining ENDS as a harm reduction approach to tobacco smoking. However, there are major concerns with this direction of research, particularly for people with SCZ. Though ENDS appear much less harmful than cigarettes, they still carry neuropsychiatric and cardiovascular consequences, and research on interventions for vaping cessation is in its infancy. Indeed, the addiction liability of ENDS in people with SCZ is unknown. It is critical that we understand how withdrawal from ENDS compares to that of cigarettes. Notably, results from the general population (like the parent study) may not generalize to SCZ as they may be more vulnerable to ENDS dependency and experience different or more severe withdrawal due to multiple disease-related factors. The proposed supplement leverages the strengths of the parent study, which focuses on the general population, and enhances its overall project impact and relevance to health disparities by recruiting a sample of people with SCZ, half of whom vape ENDS daily and half of whom smoke daily. The supplement will provide novel data on the effects of 24-hr abstinence from vaping vs smoking on self- report and objective assessments of major facets of withdrawal in people with SCZ, as well as changes in neuropsychiatric symptoms. It will also provide a novel comparison of vaping/smoking withdrawal in people with SCZ (the supplemental data) to a matched group of people without SCZ (from the parent trial) and explore candidate moderators (e.g., antipsychotic class, sex). Results will provide the first literature on ENDS withdrawal in people with SCZ, who continue to be an under-represented group in nicotine/tobacco research, despite their facing marked tobacco-related health disparities (a NIDA strategic plan cross-cutting theme). Results will directly inform the suitability of ENDS for tobacco harm reduction (NIDA strategic plan priority area #2) in people with SCZ. Moreover, the comprehensive, multi-modal assessment of withdrawal facets will directly inform the development of ENDS cessation interventions for people with SCZ.