In the midst of an escalating U.S. opioid crisis, the immediate focus of public health interventions is on fatal overdose prevention. Few studies, however, have sought to examine the long-term health consequences of exposure to repeated nonfatal opioid overdose. We reviewed recent literature to examine three corresponding downstream health outcomes of repeated overdose: a) neurodegenerative processes; b) cognition and memory; and c) overdose risk behaviours. We found a remarkable congruency among available biochemical and cognitive data on how nonfatal overdose precipitates various pathological feedforward and feedback loops that affect people who use opioids for years to come. We found however that downstream behavioural implications of neurodegenerative and cognitive sequelae are less studied despite being most proximal to an overdose. Findings point to a vicious cycle of nonfatal overdose leading to neurodegeneration - closely resembling Alzheimer Disease - that results in cognitive decline that in turn leads to potentially reduced adherence to safe drug use behaviours. The collected evidence not only brings into the focus the long-term health consequences of nonfatal overdose from the perspectives of biology, neuroscience, and public health, but also creates new cross-disciplinary context and awareness in the research and public health community that should benefit people at risk.