Naloxone dosing in the era of synthetic opioids: Applying the Goldilocks principle

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Abstract

The opioid overdose epidemic remains a critical public health crisis. In recent years, synthetic opioids like fentanyl and nitazenes, have driven a sharp rise in deaths. Naloxone, an opioid receptor antagonist, has been established as a key intervention for reversing opioid overdoses and saving lives. However, there remains a critical need to optimize naloxone dosing strategies. This article examines the challenges of both under-dosing and over-antagonism in naloxone administration, emphasizing the importance of a tailored approach to overdose management. A ‘just the right dose’ approach is essential for minimizing the risks of over-antagonism while still reversing opioid overdose. This involves starting with a modest naloxone dose and carefully titrating it based on the patient's response, considering factors such as opioid type, overdose severity, and opioid tolerance. A tailored approach to naloxone dosing may present challenges for non-medically trained responders but it can ensure that as many people as possible receive the right dose of naloxone when they need it. Training programs should also emphasize the importance of first aid and supportive care, including airway management and alerting emergency services, as well as careful monitoring of the patient's response.

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APA

Gonzalez Utrilla, M., Chesney, E., Neale, J., Metrebian, N., Kalk, N., Skulberg, A. K., … Strang, J. (2025). Naloxone dosing in the era of synthetic opioids: Applying the Goldilocks principle. Addiction, 120(11), 2165–2172. https://doi.org/10.1111/add.70060

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