# Is there an upper limit to how large of a dose of fentanyl before narcan stops working

**URL:** <https://boards.straightdope.com/t/is-there-an-upper-limit-to-how-large-of-a-dose-of-fentanyl-before-narcan-stops-working/1015188>\
**Category:** Factual Questions\
**Created:** [March 6, 2025, 12:47am UTC](https://boards.straightdope.com/t/is-there-an-upper-limit-to-how-large-of-a-dose-of-fentanyl-before-narcan-stops-working/1015188 "2025-03-06T00:47:29Z")\
**Posts on this page:** 2\
**Page:** 1

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**Author:** ![Wesley\_Clark](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/wesley_clark/32/20581_2.png) [@Wesley\_Clark](https://boards.straightdope.com/u/Wesley_Clark)\
**Post date:** [March 6, 2025, 12:47am UTC](https://boards.straightdope.com/t/is-there-an-upper-limit-to-how-large-of-a-dose-of-fentanyl-before-narcan-stops-working/1015188/1 "2025-03-06T00:47:29Z")

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I’ve heard stories from EMTs of finding someone who OD’d and the EMT having to give them multiple doses of narcan.

My understanding is the u-opioid receptor is the one that causes respiratory depression. Naloxone has a stronger binding affinity for the u-opioid receptor than fentanyl, so it should displace fentanyl from the receptor.

> **[Naloxone | Pharmacology](https://en.wikipedia.org/wiki/Naloxone#Pharmacology)**
>
> Naloxone is a lipophilic compound that acts as a non-selective and competitive opioid receptor antagonist. The pharmacologically active isomer of naloxone is (−)-naloxone. Naloxone's binding affinity is highest for the μ-opioid receptor (MOR), then the δ-opioid receptor (DOR), and lowest for the κ-opioid receptor (KOR); naloxone has negligible affinity for the nociceptin receptor.
> If naloxone is administered in the absence of concomitant opioid use, no functional pharmacological activity occurs,...

> A single administration of naloxone at a relatively high dose of 2 mg by [intravenous injection](https://en.wikipedia.org/wiki/Intravenous_injection) has been found to produce brain MOR blockade of 80% at 5 minutes, 47% at 2 hours, 44% at 4 hours, and 8% at 8 hours.[[72]](https://en.wikipedia.org/wiki/Naloxone#cite_note-ColasantiLingford-HughesNutt2013-72) A low dose (2 μg/kg) produced brain MOR blockade of 42% at 5 minutes, 36% at 2 hours, 33% at 4 hours, and 10% at 8 hours.[[72]](https://en.wikipedia.org/wiki/Naloxone#cite_note-ColasantiLingford-HughesNutt2013-72) [Intranasal administration](https://en.wikipedia.org/wiki/Intranasal_administration) of naloxone via [nasal spray](https://en.wikipedia.org/wiki/Nasal_spray) has likewise been found to rapidly occupy brain MORs, with peak occupancy occurring at 20 minutes, peak occupancies of 67% at a dose of 2 mg and 85% with 4 mg, and an estimated half-life of occupancy disappearance of approximately 100 minutes (1.67 hours).[[73]](https://en.wikipedia.org/wiki/Naloxone#cite_note-van_WaardeAbsalomVisser2020-73)[[74]](https://en.wikipedia.org/wiki/Naloxone#cite_note-pmid30867551-74)

So at 4mg, the peak receptor occupancy is at 85%. But what happens if someone takes an extremely large dose of fentanyl like 20mg or more? Is naloxone enough to block the receptors and prevent death by respiratory depression?

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**Author:** ![nearwildheaven](https://avatars.discourse-cdn.com/v4/letter/n/90db22/32.png) [@nearwildheaven](https://boards.straightdope.com/u/nearwildheaven)\
**Post date:** [March 7, 2025, 12:59am UTC](https://boards.straightdope.com/t/is-there-an-upper-limit-to-how-large-of-a-dose-of-fentanyl-before-narcan-stops-working/1015188/2 "2025-03-07T00:59:20Z")

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Naloxone is much shorter-acting than fentanyl, and other opiates, and that’s the main reason why EMTs, etc. have to give multiple doses.