Probably not. Read this absolutely brilliant piece from The Tox & The Hound here. (They did all the hard work and we stole their sources.)
Opioid "resistance" to naloxone is most likely not a thing, per se.
The reported effect from synthetic and novel opioids are unlikely to be due to the agent's binding affinity for receptors within the brain, but rather from an ability to rapidly permeate the blood brain barrier much faster than "traditional" opioids such as heroin.
Even in cases where a synthetic opioid agent was identified, the vast majority of cases did not need more than 4mg of naloxone to achieve reversal.
Intranasal (IN) naloxone is popular among many EMS agencies as well as law enforcement, fire departments, and bystanders.
IN naloxone has been shown to be effective in several randomized controlled trials for successful reversal of opioid intoxication.
However... There are important pitfalls to be cognizant of when choosing this option for delivering naloxone.
https://www.totalem.org/emergency-professionals/podcast-73-ppe-in-opiate-overdoses
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