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Abstract BackgroundOpioid overdose is the leading cause of injury-related death in the United States. Individuals who overdose outside of clinical settings have more positive clinical outcomes when they receive naloxone, an opioid antagonist, from a bystander as an early intervention before emergency personnel arrive. However, there is a gap in knowledge about successful instantaneous learning and intervention in a real-life stressful environment. The objective of this study is to explore the efficacy of different instructional delivery methods for bystanders in a stressful environment. We aim to evaluate which methods are most effective for instantaneous learning, successful intervention, and improved clinical outcomes. MethodsTo explore instantaneous learning in a stressful environment, we conducted a quantitative randomized controlled trial to measure how accurately individuals responded to memory-based survey questions guided by different instructional methods. Students from a large university in the Midwest (n = 157) were recruited in a public space on campus and accessed the six-question survey on their mobile devices. The intervention group competed the survey immediately while the research team created a distracting environment. The control group was asked to complete the survey later in a quiet environment. ResultsThe intervention group correctly answered 0.72 questions fewer than the control group (p = .000, CI [0.337, 1.103]). Questions Q1 and Q5 contained direct instructions with a verbal component and showed the greatest accuracy with over 90% correct for both stressful and controlled environments. ConclusionsThe variability in the responses suggests that there are environmental factors as well as instructional design features which influence instantaneous learning. The findings of this study begin to address the gap in knowledge about the effects of stress on instantaneous learning and the most effective types of instruction for untrained bystanders in emergency situations.