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Research analysis: Is 8 mg of naloxone better than 4 mg?

Real-world data of high-dose naloxone administration by law enforcement officers found no added benefit to opioid overdose patients


AP Photo/Matt Rourke

The New York State Department of Health partnered with the New York State Police to compare the outcome differences of an 8-mg dose of intranasal naloxone to the standard 4-mg dose of intranasal naloxone.

During the study period — March 2022 to August 2023 — NYSP troopers in three of the state’s 11 posts administered 101 8-mg doses and 253 4-mg doses at the other eight trooper posts.

All troopers receive annual opioid overdose training and the NYSP has been administering naloxone since 2014. The researchers used naloxone administration reports, as well as body-worn camera footage, to determine if patients met the inclusion criteria for the study.

The study results, reported in the CDC Morbidity and Mortality Weekly Report, found no benefit to administering the 8-mg intranasal naloxone compared to the 4-mg product. The researchers reported no difference in post-naloxone signs and symptoms, patient combativeness or hospital transport refusal. Overdose patients who receive the 8-mg intranasal naloxone overdose had a 2.51 times higher risk for opioid withdrawal signs and symptoms, including vomiting.

More detail about the research methods and statistical analysis is available in the CDC MMWR, “Comparison of Administration of 8-Milligram and 4-Milligram Intranasal Naloxone by Law Enforcement During Response to Suspected Opioid Overdose — New York, March 2022–August 2023.”

Memorable quotes

A top reason cited for creating the 8-mg intranasal naloxone product is the increasing prevalence of synthetic opioids. But at the time of the study, there wasn’t real-world quantitative evidence that 4-mg naloxone was ineffective at reversing synthetic opioid overdoses.

Here are three memorable quotes from the MMWR:

  • “The approval of the higher-concentration formulation was ... supported by reports from both the FDA Advisory Committee and the National Institutes of Health, which both suggested that higher-dose initial opioid reversal agents were needed to effectively respond to overdoses from synthetic opioids, including fentanyl.”
  • “Suggesting that, in this field test, the increased dosage did not provide added benefit, even in light of the increased prevalence of synthetic opioids, including fentanyl, in the drug supply.”
  • “Harm reduction advocates and medical professionals have noted potential harms of higher-dose naloxone, including severe withdrawal signs and symptoms, which can result in refusal of medical care, rapid reuse of opioids, reluctance to use naloxone if witnessing an overdose, and respiratory complications, including pulmonary edema and consequences of aspiration of vomitus.”
P1-Naloxone research.png

Reported outcomes and post-naloxone signs and symptoms among persons who received naloxone for suspected opioid overdose, by intranasal naloxone formulation as reported by New York State Police personnel (N = 354) — New York, March 2022-August 2023.

Top takeaways

Real-world quantitative data of naloxone administration by law enforcement officers adds to our understanding of the prehospital care of opioid overdose by laypersons, fire and law enforcement first responders, as well as EMTs and paramedics. After reviewing the MMWR, here are five top takeaways.

1. More naloxone isn’t always better

As we have learned with supplemental oxygen, more isn’t always better. The goal of treatment isn’t to restore full consciousness or induce opioid withdrawal symptoms. The primary reason we treat opioid overdose is to ensure adequate ventilation. If 4 mg of naloxone, instead of 8 mg, can be used to reverse the patient’s respiratory depression and ensure adequate ventilation, use 4 mg.

2. Use the tools available to treat opioid overdose

Naloxone is an amazing tool for opioid overdose treatment. If the 4-mg intranasal dose is the only tool on a police officer’s duty belt, they should use the tool. Other tools, including bag-valve-mask ventilation or rescue breathing, can be used until naloxone is administered.

3. Continue patient care after the overdose

Of the 8-mg dose patients, troopers documented opioid withdrawal signs or symptoms, including vomiting, in 37.6% of the patients. Another 20.8% of patients had vomiting only. In the 4-mg dose group, 19.4% were reported to have opioid withdrawal signs or symptoms, including vomiting, while 13.8% of the 4-mg dose group had vomiting only.

In addition to monitoring adequate breathing post-naloxone, responders need to anticipate vomiting and prevent aspiration. If the patient is breathing, but not responsive, put the patient in the recovery position. Even if a patient is awake, anticipate vomiting, don appropriate PPE to reduce the risk of exposure to vomitus, and if available, offer the patient an emesis bag.

4. Naloxone is an effective lifesaving drug

Naloxone, when administered to people experiencing an opioid overdose, is an incredible treatment. In this study, 100 of 101 (99%) patients who received the 8-mg intranasal naloxone dose survived. Another 249 of 253 (99.2%) patients who received the 4-mg intranasal dose survived. Widely distributing naloxone to laypeople; friends and family of narcotic drug users; first responders; and in any business, school or building, is an outstanding public health intervention to help keep opioid drug users alive until they are ready for treatment.

5. Law enforcement naloxone administration is saving lives

The New York State Patrol naloxone administration has undoubtedly saved hundreds of lives since it began in 2014. The NYSP troopers and thousands of other law enforcement officers who are trained to recognize and treat a narcotic overdose with naloxone are making a difference in their community.

Greg Friese, MS, NRP, is the Lexipol Editorial Director, leading the efforts of the editorial team on Police1, FireRescue1, Corrections1, EMS1 and Gov1. Greg has a bachelor’s degree from the University of Wisconsin-Madison and a master’s degree from the University of Idaho. He is an educator, author, paramedic and runner. Greg is a three-time Jesse H. Neal award winner, the most prestigious award in specialized journalism, and 2018 and 2020 Eddie Award winner for best Column/Blog. Ask questions or submit article ideas to Greg by emailing him at and connect with him on LinkedIn.