A recent podcast of Radiolab (time index 3:05) described a person who had overdosed given the nasal spray form of Narcan. The report indicated the patient was awake seconds after the spray was administered to both nostrils. If this is true, how does it work so fast?

The limit of my knowledge of biology and of Narcan is it binds with opioid receptors. As I understand it opioid receptors which are located in the brain, in the spinal cord, on peripheral neurons. Which receptors does the Narcan spray bind with that it works so fast?

Could this be answered in layman's terms?


1 Answer 1


Q: The report indicated the patient was awake seconds after the spray was administered to both nostrils. If this is true, how does it work so fast?

This is possibly an exaggeration, although intranasal Narcan can have a rapid clinical response time:

Tania Mieke Robertson, Gregory W. Hendey, Geoff Stroh & Marc Shalit, Intranasal Naloxone Is a Viable Alternative to Intravenous Naloxone for Prehospital Narcotic Overdose, Prehospital Emergency Care, 2009, 13:4,512-515, doi:10.1080/10903120903144866

We included patients with suspected narcotic overdose treated in the prehospital setting over 17 months, between March 2003 and July 2004. Paramedics documented dose, route of administration, and positive response times using an electronic record. Clinical response was defined as an increase in respiratory rate (breaths/min)...

The mean time between naloxone administration and clinical response was longer for the IN group (12.9 vs. 8.1 min, p = 0.02). However, the mean times from patient contact to clinical response were not significantly different between the IN and IV groups (20.3 vs. 20.7 min, p = 0.9).

Since it takes time to establish IV access, there isn't a difference between IN and IV Narcan administration in terms of "time from patient contact to clinical response." That said, IN takes ~5 minutes longer than IV (~13 vs 8 minutes) from administration to onset of action.

Amanda Robinson, Daniel P. Wermeling, Intranasal naloxone administration for treatment of opioid overdose, American Journal of Health-System Pharmacy, 2014 71:24,2129–2135, doi:10.2146/ajhp130798

Case reports

In the department of emergency medicine of Western Hospital in Melbourne, Australia, six cases of acute heroin overdose were successfully reversed using intranasal administration of naloxone hydrochloride, with all patients exhibiting a return of spontaneous respiration within two minutes. The doses used in these cases ranged from 0.8 to 2 mg at the treating physician’s discretion, and the time to spontaneous respiration ranged from 30 seconds to two minutes. While this study only looked at data from six isolated cases of acute heroin overdose, the results were encouraging and led to a larger prospective clinical trial comparing the safety and efficacy of intranasal versus intramuscular naloxone administration.

So, there are reports of IN Narcan responses in less than one minute. The instant response described in the podcast might be artistic license at work, but it's not impossible that a patient could respond on the order of seconds.

Q: Which receptors does the Narcan spray bind with that it works so fast?

Robinson and Wermeling, 2014 (above)

Naloxone is an opioid-receptor antagonist, with evidence indicating high affinity for μ-opioid receptors; it is used in the treatment of opioid overdose to reverse central nervous system (CNS) depression and restore respiration.

Naloxone is a pure opioid antagonist with no agonist activity. Prepared from thebaine, a natural opiate alkaloid, naloxone is a synthetic congener of oxymorphone. While naloxone’s mechanism of action is not fully understood, evidence suggests that the drug works by out-competing other opioids for the μ-, κ-, and σ-opioid receptor sites in the CNS, with a greater affinity for the μ-opioid receptor.

The nasal mucosa has a rich blood supply that contributes to efficient drug absorption and transport to systemic circulation. Administering drugs via this route generally avoids the first-pass hepatic metabolism seen with oral administration and leads to rapid systemic and CNS effects.


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