Study Finds Naloxone May Not Fully Reverse Potent Opioid Overdoses

Researchers warn that current overdose protocols need to be updated as opioid crisis evolves

Apr. 14, 2026 at 2:36am

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A ghostly, translucent X-ray photograph of an opioid pill or capsule, glowing against a dark background to symbolize the hidden dangers of potent synthetic opioids.An X-ray view reveals the hidden potency of newer synthetic opioids that can be harder to reverse with standard naloxone doses.Chicago Today

A new study published in the journal Anesthesiology reveals that the standard doses of naloxone may not be sufficient to fully reverse overdoses caused by newer, more potent synthetic opioids like fentanyl and sufentanil. The findings raise concerns that current overdose response guidelines developed for older, weaker opioids may need to be updated as the opioid crisis continues to change.

Why it matters

The study's findings are significant as fentanyl and fentanyl-like drugs now account for the majority of overdose deaths in the United States. Because these newer synthetic opioids bind more tightly to opioid receptors, they can be harder to reverse with a standard dose of naloxone, especially in people exposed to high levels or more potent drugs. This highlights the need to update overdose response protocols to address the evolving opioid crisis.

The details

The study, which included 30 participants, found that while naloxone can be lifesaving, a single dose may not always completely reverse respiratory depression caused by powerful synthetic opioids. The researchers tested naloxone's effectiveness in both people who had never used opioids and those who used them every day. They found that the current doses of naloxone may not be sufficient to reverse overdoses caused by newer synthetic opioids like fentanyl and sufentanil.

  • The study was published in the May 2026 issue of Anesthesiology, the peer-reviewed medical journal of the American Society of Anesthesiologists (ASA).

The players

Maarten A. van Lemmen

The lead author of the study and a researcher at the Department of Anesthesiology and Anesthesia and Pain Research Unit at Leiden University Medical Center in Leiden, the Netherlands.

James P. Rathmell

The editor-in-chief of Anesthesiology and a Professor of Anaesthesia at Harvard Medical School.

Steven E. Kern

An Adjunct Associate Professor of Anesthesiology and Bioengineering at the University of Utah.

American Society of Anesthesiologists (ASA)

An educational, research and scientific society with more than 60,000 members organized to advance the medical practice of anesthesiology and secure its future.

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What they’re saying

“Our study shows that the current doses of naloxone may not be sufficient to reverse overdoses caused by newer synthetic opioids.”

— Maarten A. van Lemmen, Study lead author

“This distinction has immediate implications for patient safety, observation practices, and dosing strategies, and helps explain why resedation and delayed respiratory instability continue to occur despite timely naloxone administration.”

— James P. Rathmell, Anesthesiology editor-in-chief and Professor of Anaesthesia at Harvard Medical School

“This distinction has immediate implications for patient safety, observation practices, and dosing strategies, and helps explain why resedation and delayed respiratory instability continue to occur despite timely naloxone administration.”

— Steven E. Kern, Adjunct Associate Professor of Anesthesiology and Bioengineering, University of Utah

What’s next

The study authors emphasize that because naloxone is less reliable against stronger opioids, it is vital to call 911 immediately when an overdose is suspected, even if naloxone has been administered. The effects of naloxone may wear off quickly, and additional doses may be needed to keep the person safe until medical help arrives. Current overdose response guidelines were developed for older, weaker opioids, so there is an urgent need to update practices and design better tools as opioid misuse continues to change.

The takeaway

This study highlights the growing challenges in reversing opioid overdoses, especially those involving newer, more potent synthetic drugs like fentanyl and sufentanil. It underscores the need for updated overdose response protocols and better tools to address the evolving opioid crisis and save lives.