Study results raise concern about naloxone efficacy against some synthetic opioids

A single dose of naloxone may not always completely reverse respiratory depression caused by powerful synthetic opioids, study results have suggested.

Publishing their findings in the upcoming May issue of Anesthesiology, researchers noted the effectiveness of 4mg intranasal naloxone in reversing moderate levels of opioid-induced respiratory depression (OIRD; 30–40% decrease in V_e) with faster reversal of V_e than end-tidal pCO₂ by a factor of at least 3. 

However, reversal dynamics and magnitudes vary across physiologic endpoints, study authors said.

“Ventilation recovers faster than end-tidal pCO₂ and pupil diameter, and no recovery in end-tidal pCO₂ was observed in opioid-naive individuals exposed to sufentanil.

“Our current data suggest that a single dose of Narcan [naloxone] is unlikely to serve as an adequate countermeasure in the event of exposure to high-dose or high-affinity opioids,” they added.

Calling emergency services is vital when an overdose is suspected, even if naloxone — used to temporarily reverse an opioid overdose — has been administered, the study authors stressed.

Leaders from UK charity Waythrough have warned that while some of the substances mentioned in the study were not often seen in circulation in the UK, the introduction of synthetic opioids to the illicit drug market was “of significant concern”.

Jon Findlay, harm reduction lead for Waythrough and Patrick Gorey, regional lead pharmacist at Waythrough, told The Pharmaceutical Journal: “[In current UK practice], naloxone still remains to be effective in the reversal of opioid overdose… we continue to advocate for the ongoing use and distribution of naloxone.”

In March 2025, the Scottish Drug Forum warned that multiple doses of naloxone may be needed to reverse drug overdoses, following the discovery of synthetic opioids in various street drugs in Scotland.

While naloxone is a prescription-only medication, pharmacists are among named professionals who can provide a take-home naloxone supply without a prescription. In addition, some community pharmacies keep a supply of the drug on site.

In December 2025, the Department for Health and Social Care launched a consultation on whether to make naloxone could be available without a prescription at hostels, day centres and homeless outreach services, as well as at border control and forensic labs.