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The goal of this FOA is to test the feasibility and safety of treatment protocols for rapid-acting interventions that have the potential to reduce severe suicide risk. Approaches considered should be feasibly integrated into existing appropriate healthcare settings, such as emergency departments (ED), psychiatric inpatient units, and/or settings that may need to meet Risk Evaluation and Mitigation Strategy (REMS) approaches. Of interest are promising, existing interventions that include pharmacological, psychosocial/behavioral, and device-based approaches, alone or in combination. Approaches should build upon extant intervention findings regarding efficacy, dosing, durability of effects, patient selection/matching, and safety. Principal outcomes of interest are the reduction of suicide events, including ideation, attempts, death, and the potential decrease in high resource utilization (e.g., ED visits, hospitalization). This FOA uses the R01 grant mechanism and invites clinical research applications that will build foundational work for larger trials that could expand the evidence base for rapid-acting treatments for youth and adults with severe suicide risk.