Policy Brief

Naloxone for Opioid Overdose: Life-Saving Science
Naloxone for Opioid Overdose: Life-Saving Science

This is Archived Content. This content is available for historical purposes only. It may not reflect the current state of science or language from the National Institute on Drug Abuse (NIDA). Find current research and publications at nida.nih.gov.

Author: National Institute on Drug Abuse

Naloxone Saves Lives

Naloxone can quickly restore normal breathing and save the life of a person who is overdosing on opioids. In 2017, over 47,600 people died from an overdose on opioid drugs, including prescription pain relievers, heroin, and fentanyl.1 Naloxone is a safe medication that is widely used by emergency medical personnel and other first responders to prevent opioid overdose deaths. Unfortunately, by the time a person having an overdose is reached, it is often too late.

Friends, family, and other bystanders can save lives with naloxone. Naloxone distribution programs give naloxone kits to opioid users, their friends and families, and others who may find themselves in a position to save the life of someone at risk of an opioid overdose.

  • A naloxone distribution program in Massachusetts reduced opioid overdose deaths, without increasing opioid use, by an estimated 11 percent in the nineteen communities that implemented the program.2
  • A large-scale national study showed that opioid overdose deaths decreased by 14 percent in states after they enacted naloxone access laws.3
  • Statistical modeling suggests that high rates of naloxone distribution among laypersons and emergency personnel could avert 21 percent of opioid overdose deaths, and the majority of overdose death reduction would result from increased distribution to laypersons.4

How Does Naloxone Work?

Naloxone is an opioid receptor antagonist meaning it binds to opioid receptors and reverses or blocks the effects of other opioids. Giving naloxone rapidly reverses the effects of opioid drugs, restoring normal respiration. It can be administered by injection or through a nasal spray.

Is Naloxone Safe?

Yes. There is no evidence of significant adverse reactions to naloxone.5 Administering naloxone in cases of opioid overdose can cause withdrawal symptoms when the person is dependent on opioids; this is uncomfortable without being life threatening.6, 7 The risk that someone overdosing on opioids will have a serious adverse reaction to naloxone is far less than their risk of dying from overdose.8, 9 Naloxone works if a person has opioids in their system and has no harmful effect if opioids are absent. Naloxone should be given to any person who shows signs of an opioid overdose or when an overdose is suspected.10

Is there a Preferable Delivery System?

All systems used by first responders deliver the stated dose of naloxone and can be highly effective in reversing an opioid overdose. Naloxone comes in two FDA-approved forms: injectable and prepackaged nasal spray. Study findings released in March 2019 suggests that the FDA-approved naloxone devices produce substantially higher blood levels of naloxone than improvised nasal devices.11 These results suggest that the FDA-approved forms are preferable over non-FDA-approved forms.

Science Driven Solutions

User-Friendly Naloxone

In 2015, the FDA approved the first naloxone nasal spray—NARCAN®−developed as a result of NIDA-funded research.12, 13 In 2019, the FDA approved the first generic naloxone nasal spray.14 In 2021, the FDA approved a higher dose naloxone nasal spray—KLOXXADO®.15  Increasing access to naloxone is a priority for the U.S. Department of Health and Human Services, and research funded by NIDA is developing strategies to identify people at risk and ensure they have access to naloxone in the event of an overdose.

Identifying At-Risk Patients 

A survey given to chronic pain patients receiving prescription opioids found that nearly 1 in 5 had experienced an overdose and more than half engaged in high-risk behaviors, including combining opioids with alcohol. While only 3% of patients surveyed reported having a naloxone prescription or being trained to deliver naloxone, nearly 40% had witnessed an overdose.16 Another study found 68% of participants recruited from syringe service programs, detoxification, or opioid treatment programs had witnessed an overdose but only 17% had a prescription for naloxone.17

Co-Prescribing Naloxone to At-Risk Patients

NIDA-funded researchers are evaluating interventions to improve opioid prescribing practices, including the co-prescription of naloxone. An early study found that giving naloxone to patients on opioid therapy for chronic pain was associated with fewer opioid-related emergency department visits, especially among patients receiving high doses of prescription opioids. This study will help to inform implementation efforts that can increase access to naloxone.5

Co-Prescribing Naloxone with Prescription Opioids

NIDA-funded researchers are evaluating interventions to improve opioid prescribing practices, including the co-prescription of naloxone. An early study found that giving naloxone to patients on opioid therapy for chronic pain was associated with fewer opioid-related emergency department visits, especially among patients receiving high doses of prescription opioids.18 Some research suggests that when clinicians prescribe naloxone along with prescription opioids, the risk of opioid overdose decreases even if the naloxone prescription does not get filled. In 2016, the CDC began recommending co-prescriptions in some cases, as detailed in guidance issued by HHS in 2018 and as codified in law by several states.19-21 A 2019 study of Medicare Part D patients showed an overall increase in national rates for naloxone co-prescription along with any opioid.22

Good Samaritan Laws for Naloxone

As of December 2018, forty-six states and the District of Columbia provided legal immunity for friends, family, and other bystanders, or “Good Samaritans,” seeking medical aid for someone experiencing an opioid overdose.20

After Naloxone is Given

Bystanders: Call 911 Immediately

It is important to call emergency responders right away. Naloxone is only active in the body for 30 to 90 minutes and its effects could wear off before those of the opioids, causing the user to stop breathing again. People who are given naloxone should be observed constantly until emergency care arrives.

Repeat Naloxone Dosing if Needed

Overdoses involving highly potent synthetic opioids (e.g., fentanyl) or large quantities of opioids may require multiple doses of naloxone. If respiratory function does not improve, naloxone doses may be repeated every two to three minutes.23

Clinicians: Screen for Opioid Use Disorder

An overdose reversal is a critical opportunity to identify people with opioid use disorder and engage them in treatment.

Where Can I Get Naloxone?

Naloxone can be purchased in many pharmacies, in many states, without bringing in a prescription. The majority of states allow prescribing and dispensing of naloxone to family members and friends in addition to people receiving prescription opioids for pain or with opioid use disorder.14 Law enforcement, emergency medical services, and community-based naloxone distribution programs can apply to be a Qualified Purchaser or work with their state or local health department to order naloxone. To find naloxone in your area, go to the Naloxone Finder.

Where Can I Get More Information?

If you or someone you care about has an opioid use disorder:

Solutions Driven Science

Reaching Communities in Need 

From 1999 through 2017, drug overdose deaths increased in both urban and rural communities. In 2017, overdose death rates involving heroin and synthetic opioids were higher in urban areas, and those involving natural and semisynthetic opioids were higher in rural areas.24 NIDA is funding research that addresses the dramatic increase of opioid misuse and its consequences in both urban and rural areas hit hardest by the opioid epidemic. Through the NIH Helping to End Addiction Long-termSM (HEAL) Initiative, NIDA and SAMHSA fund the large-scale HEALing Communities Study to implement and test integrated evidence-based practices–including the distribution of naloxone– across health care, behavioral health, justice and other community settings. Based on pilot work in partnership with the Appalachian Regional Commission, NIDA is supporting research in Appalachia that will identify community-specific factors that contribute to the high rates of opioid misuse, overdose deaths, and the related spread of infectious disease and will identify promising evidence-based prevention and treatment interventions – including naloxone provision for overdose treatment–to address these factors and improve public health outcomes.

Facilitating Access to Naloxone

All 50 states and the District of Columbia have passed legislation to improve layperson naloxone access, and in most states, laypersons can receive naloxone from a pharmacy under a standing order (i.e., without an individual prescription) or its functional equivalent.25 In 2018, the U.S. Surgeon General called for heightened awareness and greater availability of naloxone.26 In 2019, the FDA issued a statement on its continued efforts to increase the availability of all approved forms of naloxone.27 Yet, an August 2019 CDC report revealed that too little naloxone is dispensed in many areas that need it most.10

NIDA-funded studies are addressing key barriers and facilitators to naloxone access. Current projects include assessing the implementation of pharmacy-based naloxone access and its association with opioid-overdose mortality rates; programs to scale up overdose education and naloxone distribution in community settings, pharmacies, and justice settings; pharmacy-focused training to increase naloxone dispensing to patients who may be at risk for opioid overdose; and use of naloxone by law enforcement and its impact on referrals to treatment and on the rates of 911 use by witnesses of opioid overdose.

Longer-Acting Reversal Agents

NIDA is funding research on the development of new longer-acting overdose-reversal medications to more effectively reverse overdose from powerful synthetic opioids such as fentanyl. Focusing on longer-action opioid antagonists, researchers are working to develop an intranasal formulation of nalmefene (previously approved by the FDA in an injectable formulation) and are examining the potential for methocinnamox (MCAM) as a longer-acting reversal agent.

Technologies to Detect and Reverse Overdose

Preliminary findings from NIDA-funded research show promise for a wearable device that can administer a large dose of naloxone when the device detects overdose-induced respiratory failure.28 Early findings from other researchers suggest that a smartphone app may be able to identify breathing problems and other physical symptoms associated with acute opioid toxicity, providing an early warning that an opioid overdose reversal agent is needed.29

 

References

  1. Scholl L, S.P., Kariisa M, Wilson N, Baldwin G. Drug and Opioid-Involved Overdose Deaths - United States, 2013-2017 Morbidity and Mortality Weekly Report [MMWR] 2018; Available from: https://www.cdc.gov/mmwr/volumes/67/wr/mm675152e1.htm.
  2. Walley, A.Y., et al., Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis. BMJ, 2013. 346(jan30 5): p. f174-f174.
  3. McClellan, C., et al., Opioid-overdose laws association with opioid use and overdose mortality. Addictive Behaviors, 2018. 86: p. 90-95.
  4. Townsend, T., et al., Cost-effectiveness analysis of alternative naloxone distribution strategies: First responder and lay distribution in the United States. International Journal of Drug Policy, 2019.
  5. Wermeling, D.P., Review of naloxone safety for opioid overdose: practical considerations for new technology and expanded public access. Therapeutic Advances in Drug Safety, 2015. 6(1): p. 20-31.
  6. Belz, D., et al., Naloxone Use in a Tiered-Response Emergency Medical Services System. Prehospital Emergency Care, 2006. 10(4): p. 468-471.
  7. Buajordet, I., et al., Adverse events after naloxone treatment of episodes of suspected acute opioid overdose. European Journal of Emergency Medicine, 2004. 11(1): p. 19-23.
  8. Darke, S., R.P. Mattick, and L. Degenhardt, The ratio of non-fatal to fatal heroin overdose. Addiction, 2003. 98(8): p. 1169-1171.
  9. Osterwalder, J.J., Naloxone–For Intoxications with Intravenous Heroin and Heroin Mixtures-Harmless or Hazardous? A Prospective Clinical Study. Journal of Toxicology: Clinical Toxicology, 1996. 34(4): p. 409-416.
  10. CDC. Still Not Enough Naloxone Where It's Most Needed [news release]. 2019; Available from: https://www.cdc.gov/media/releases/2019/p0806-naloxone.html.
  11. Krieter, P.A., et al., Comparison of the Pharmacokinetic Properties of Naloxone Following the Use of FDA‐Approved Intranasal and Intramuscular Devices Versus a Common Improvised Nasal Naloxone Device. The Journal of Clinical Pharmacology, 2019. 59(8): p. 1078-1084.
  12. NIDA. NARCAN Nasal Spray: Live-Saving Science at NIDA [news release]. 2015; Available from: archives.nida.nih.gov/news-events/noras-blog/2015/11/narcan-nasal-spray-life-saving-science-nida.
  13. FDA. FDA moves quickly to approve easy-to-use nasal spray to treat opioid overdose [news release]. 2015; Available from: http://wayback.archive-it.org/7993/20170111122937/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm473505.htm.
  14. FDA. FDA approves first generic naloxone nasal spray to treat opioid overdose [news release]. 2019; Available from: https://www.fda.gov/news-events/press-announcements/fda-approves-first-generic-naloxone-nasal-spray-treat-opioid-overdose.
  15. U.S. Food and Drug Administration. FDA approves higher dosage of naloxone nasal spray to treat opioid overdose. FDA news release April 30, 2021 https://www.fda.gov/news-events/press-announcements/fda-approves-higher-dosage-naloxone-nasal-spray-treat-opioid-overdose] 
  16. Dunn, K.E., et al., Opioid Overdose History, Risk Behaviors, and Knowledge in Patients Taking Prescribed Opioids for Chronic Pain. Pain Medicine, 2016: p. pnw228.
  17. Dunn, K.E., et al., Opioid Overdose Experience, Risk Behaviors, and Knowledge in Drug Users from a Rural Versus an Urban Setting. Journal of Substance Abuse Treatment, 2016. 71: p. 1-7.
  18. Coffin, P.O., et al., Nonrandomized Intervention Study of Naloxone Coprescription for Primary Care Patients Receiving Long-Term Opioid Therapy for Pain. Annals of Internal Medicine, 2016. 165(4): p. 245.
  19. Dowell D, H.T., Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. Morbidity and Mortality WEekly Report (MMWR) 2016.
  20. NPHL. Legal Interventions to Reduce Overdose Mortality: Naloxone Access and Overdose Good Samaritan Laws. 2018; Available from: https://www.networkforphl.org/_asset/qz5pvn/network-naloxone-10-4.pdf.
  21. HHS. Naloxone: The Opioid Reversal Drug that Saves Lives. 2018; Available from: https://www.hhs.gov/opioids/sites/default/files/2018-12/naloxone-coprescribing-guidance.pdf.
  22. NIDA. Co-prescribing naloxone in Medicare Part D increases [news release]. 2019; Available from: https://archives.nida.nih.gov/news-events/news-releases/2019/08/co-prescribing-naloxone-in-medicare-part-d-increases.
  23. SAMHSA. SAMHSA Opioid Overdose Prevention Toolkit. 2018; Available from: https://store.samhsa.gov/system/files/sma18-4742.pdf.
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  25. NPHL. Legal Efforts to Reduce Barriers to Accessing the Anti-overdose Medication Naloxone. 2017; Available from: https://www.networkforphl.org/resources_collection/2017/08/29/921/legal_efforts_to_reduce_barriers_to_accessing_the_anti-overdose_medication_naloxone.
  26. HHS. U.S. Surgeon General's Advisory on Naloxone and Opioid Overdose [news release]. 2018; Available from: https://www.hhs.gov/surgeongeneral/priorities/opioids-and-addiction/naloxone-advisory/index.html.
  27. FDA. Statement on continued efforts to increase availability of all forms of naloxone to help reduce opioid overdose deaths [news release]. 2019; Available from: https://www.fda.gov/news-events/press-announcements/statement-continued-efforts-increase-availability-all-forms-naloxone-help-reduce-opioid-overdose?utm_campaign=092019_Statement_FDA%E2%80%99s%20efforts%20to%20increase%20availability%20of%20all%20forms%20of%20naloxone&utm_medium=email&utm_source=Eloqua.
  28. Dhowan, B., et al., Simple minimally-invasive automatic antidote delivery device (A2D2) towards closed-loop reversal of opioid overdose. Journal of Controlled Release, 2019. 306: p. 130-137.
  29. Nandakumar, R., S. Gollakota, and J.E. Sunshine, Opioid overdose detection using smartphones. Science Translational Medicine, 2019. 11(474): p. eaau8914.

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