Naloxone

File:NaloxoneKit.jpg

Naloxone is useful in treating both acute opioid overdose and respiratory or mental depression due to opioids. Whether it is useful in those in cardiac arrest due to an opioid overdose is unclear.{{cite journal | vauthors = Lavonas EJ, Drennan IR, Gabrielli A, Heffner AC, Hoyte CO, Orkin AM, Sawyer KN, Donnino MW | title = Part 10: Special Circumstances of Resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care | journal = Circulation | volume = 132 | issue = 18 Suppl 2 | pages = S501–S518 | date = November 2015 | pmid = 26472998 | doi = 10.1161/cir.0000000000000264 | doi-access = free | title-link = doi }}

It is included as a part of emergency overdose response kits distributed to heroin, fentanyl, and other opioid drug users, and to emergency responders. This has been shown to reduce rates of deaths due to overdose.{{cite journal | vauthors = Maxwell S, Bigg D, Stanczykiewicz K, Carlberg-Racich S | title = Prescribing naloxone to actively injecting heroin users: a program to reduce heroin overdose deaths | journal = Journal of Addictive Diseases | volume = 25 | issue = 3 | pages = 89–96 | year = 2006 | pmid = 16956873 | doi = 10.1300/J069v25n03_11 | s2cid = 17246459 }} A prescription for naloxone is recommended if a person is on a high dose of opioid (>100{{nbsp}}mg of morphine equivalence/day), is prescribed any dose of opioid accompanied by a benzodiazepine, or is suspected or known to use opioids nonmedically.{{cite web |title=Project Lazarus, Wilkes County, North Carolina |work=Policy Briefing Document Prepared for the North Carolina Medical Board in Advance of the Public Hearing Regarding Prescription Naloxone |year=2007 |location=Raleigh, NC |url=http://intranasal.net/Peer%20Reviewed%20literature/Project%20Lazarus,%20North%20Carolina%20IN%20Naloxone%202007.pdf |access-date=20 March 2022 |archive-date=26 May 2022 |archive-url=https://web.archive.org/web/20220526182242/http://intranasal.net/Peer%20Reviewed%20literature/Project%20Lazarus,%20North%20Carolina%20IN%20Naloxone%202007.pdf |url-status=live }}{{page needed|date=February 2014}}{{verify source|date=February 2014}} Prescribing naloxone should be accompanied by standard education that includes preventing, identifying, and responding to an overdose; rescue breathing; and calling emergency services.{{cite journal | vauthors = Bowman S, Eiserman J, Beletsky L, Stancliff S, Bruce RD | title = Reducing the health consequences of opioid addiction in primary care | journal = The American Journal of Medicine | volume = 126 | issue = 7 | pages = 565–571 | date = July 2013 | pmid = 23664112 | doi = 10.1016/j.amjmed.2012.11.031 }}

Distribution of naloxone to individuals likely to encounter people who overdose is one aspect of harm reduction strategies.{{cite book | veditors = Marlatt GA, Larimer ME, Witkiewitz K | date = 2011 | title = Harm reduction: Pragmatic strategies for managing high-risk behaviors. | edition = 2nd | location = New York | publisher = Guilford Press | isbn = 978-1-4625-0256-1 }}

However, with opioids that have longer half-lives, respiratory depression returns after naloxone has worn off; therefore, adequate dosing and continuous monitoring may be necessary.{{cite journal | vauthors = van Dorp E, Yassen A, Dahan A | title = Naloxone treatment in opioid addiction: the risks and benefits | journal = Expert Opinion on Drug Safety | volume = 6 | issue = 2 | pages = 125–132 | date = March 2007 | pmid = 17367258 | doi = 10.1517/14740338.6.2.125 | s2cid = 11650530 }}

Naloxone can also be used as an antidote in an overdose of clonidine, a medication that lowers blood pressure.{{cite journal | vauthors = Niemann JT, Getzug T, Murphy W | title = Reversal of clonidine toxicity by naloxone | journal = Annals of Emergency Medicine | volume = 15 | issue = 10 | pages = 1229–1231 | date = October 1986 | pmid = 3752658 | doi = 10.1016/s0196-0644(86)80874-5 }} Clonidine overdoses are of special relevance for children, in whom even small doses can cause significant harm.{{cite journal | vauthors = Ahmad SA, Scolnik D, Snehal V, Glatstein M | title = Use of naloxone for clonidine intoxication in the pediatric age group: case report and review of the literature | journal = American Journal of Therapeutics | volume = 22 | issue = 1 | pages = e14–e16 | date = 2015 | pmid = 23782760 | doi = 10.1097/MJT.0b013e318293b0e8 }} However, there is controversy regarding naloxone's efficacy in treating the symptoms of clonidine overdose, namely slow heart rate, low blood pressure, and confusion/somnolence. Case reports that used doses of 0.1{{nbsp}}mg/kg (maximum of 2{{nbsp}}mg/dose) repeated every 1–2 minutes (10{{nbsp}}mg total dose) have shown inconsistent benefit. As the doses used throughout the literature vary, it is difficult to form a conclusion regarding the benefit of naloxone in this setting.{{cite journal | vauthors = Seger DL | title = Clonidine toxicity revisited | journal = Journal of Toxicology. Clinical Toxicology | volume = 40 | issue = 2 | pages = 145–155 | date = 2002 | pmid = 12126186 | doi = 10.1081/CLT-120004402 | s2cid = 2730597 }} The mechanism for naloxone's proposed benefit in clonidine overdose is unclear. Still, it has been suggested that endogenous opioid receptors mediate the sympathetic nervous system in the brain and elsewhere in the body.

Naloxone is poorly absorbed when taken orally or sublingually, so it is often combined with several oral or sublingual opioid preparations, including buprenorphine and pentazocine, so that when swallowed or taken sublingually, only the non-naloxone opioid has an effect.{{cite journal | vauthors = Orman JS, Keating GM | title = Buprenorphine/naloxone: a review of its use in the treatment of opioid dependence | journal = Drugs | volume = 69 | issue = 5 | pages = 577–607 | date = 2009 | pmid = 19368419 | doi = 10.2165/00003495-200969050-00006 | s2cid = 209147406 }} However, if the combination is injected (such as by dissolving a pill or sublingual strip in water), the naloxone is believed to block the effect of the other opioid. This combination is used to prevent non-medical use.

However, SAMHSA's clinical guidelines state that if the combination of buprenorphine and naloxone is injected by a regular user of buprenorphine or buprenorphine/naloxone, then the buprenorphine would still produce an agonist effect but the naloxone would fail to produce an antagonist effect. This is because the amount of naloxone that would be required to block the buprenorphine after injection is much larger than the amount that is contained in buprenorphine/naloxone (Suboxone) pills and strips. If someone who is not physically dependent on opioids were to inject the buprenorphine/naloxone combination, then the effects of the buprenorphine may at most be slightly lessened, but the individual would still be expected to experience euphoric effects.{{cite book | vauthors=((Center for Substance Abuse Treatment)) | title=Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction | series=SAMHSA/CSAT Treatment Improvement Protocols | page=23| publisher=U.S. Substance Abuse and Mental Health Services Administration (SAMHSA) | date=2004 | url=https://www.ncbi.nlm.nih.gov/books/NBK64245/ | pmid=22514846 }}

A 2003 meta-analysis of existing research showed naloxone to improve blood flow in patients with shock, including septic, cardiogenic, hemorrhagic, or spinal shock, but could not determine if this reduced patient deaths.{{cite journal | vauthors = Boeuf B, Poirier V, Gauvin F, Guerguerian AM, Roy C, Farrell CA, Lacroix J | title = Naloxone for shock | journal = The Cochrane Database of Systematic Reviews | issue = 4 | pages = CD004443 | date = 2003 | volume = 2010 | pmid = 14584016 | doi = 10.1002/14651858.CD004443 | pmc = 9036847 }}

Oral naloxone has been used for opioid-induced constipation (OIC). A 2018 meta-analysis cites 5 studies that tests it for this purpose. It found that medical treatment for OIC can be more efficacious than placebo, but did not look into the effect of individual treatments such as naloxone. As a result, no conclusion can be drawn from the study on naloxone's effectiveness for OIC.{{cite journal | vauthors = Nusrat S, Syed T, Saleem R, Clifton S, Bielefeldt K | title = Pharmacological Treatment of Opioid-Induced Constipation Is Effective but Choice of Endpoints Affects the Therapeutic Gain | journal = Digestive Diseases and Sciences | volume = 64 | issue = 1 | pages = 39–49 | date = January 2019 | pmid = 30284134 | doi = 10.1007/s10620-018-5308-9 }}

Whether naloxone is excreted in breast milk is unknown, however, it is not orally bioavailable and therefore is unlikely to affect a breastfeeding infant.{{cite news|url=https://www.drugs.com/breastfeeding/naloxone.html|title=Naloxone use while Breastfeeding|work=Drugs.com|access-date=15 August 2018|archive-date=2 November 2020|archive-url=https://web.archive.org/web/20201102082637/https://www.drugs.com/breastfeeding/naloxone.html|url-status=live}}

Naloxone can be used on infants who were exposed to intrauterine opiates administered to mothers during delivery. However, there is insufficient evidence for the use of naloxone to lower cardiorespiratory and neurological depression in these infants.{{cite journal | vauthors = Moe-Byrne T, Brown JV, McGuire W | title = Naloxone for opioid-exposed newborn infants | journal = The Cochrane Database of Systematic Reviews | volume = 2018 | issue = 10 | pages = CD003483 | date = October 2018 | pmid = 30311212 | pmc = 6517169 | doi = 10.1002/14651858.CD003483.pub3 }} Infants exposed to high concentrations of opiates during pregnancy may have CNS damage in the setting of perinatal asphyxia. Naloxone has been studied to improve outcomes in this population, however the evidence is currently weak.{{cite journal | vauthors = McGuire W, Fowlie PW, Evans DJ | title = Naloxone for preventing morbidity and mortality in newborn infants of greater than 34 weeks gestation with suspected perinatal asphyxia | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD003955 | date = 26 January 2004 | volume = 2010 | pmid = 14974047 | pmc = 6485479 | doi = 10.1002/14651858.CD003955.pub2 | publisher = John Wiley & Sons, Ltd }}

Intravenous, intramuscular, or subcutaneous administration of naloxone can be given to children and neonates to reverse opiate effects. The American Academy of Pediatrics recommends only intravenous administration as the other two forms can cause unpredictable absorption. After a dose is given, the child should be monitored for at least 24 hours. For children with low blood pressure due to septic shock, naloxone safety and effectiveness are not established.{{cite web|url=https://www.rxlist.com/narcan-drug.htm|title=Narcan (Naloxone Hydrochloride Injection): Side Effects, Interactions, Warning, Dosage & Uses|website=RxList|access-date=24 October 2019|archive-date=11 November 2020|archive-url=https://web.archive.org/web/20201111191403/https://www.rxlist.com/narcan-drug.htm|url-status=live}}

For patients 65 years and older, it is unclear if there is a difference in response. However, older people often have decreased liver and kidney function which may lead to an increased level of naloxone in their body.

In hospital settings, naloxone is injected intravenously, with an onset of 1–2 minutes and a duration of up to 45 minutes.{{cite book |title=Drug information handbook for advanced practice nursing: a comprehensive resource for nurse practitioners, nurse midwives, and clinical specialists, including selected disease management guidelines. |date=2013|publisher=Lexicomp|isbn=978-1591953234|oclc=827841946}}

Naloxone can also be administered via intramuscular or subcutaneous injection. The onset of naloxone provided through this route is 2 to 5 minutes with a duration of around 30–120min.{{cite web | title = Naloxone for Treatment of Opioid Overdose | date = October 2016 | url = https://www.fda.gov/media/100429/download | author = Advisory Committee | work = Insys Development Company, Inc. | publisher = U.S. Food and Drug Administration }} Naloxone administered intramuscularly are provided through pre-filled syringes, vials, and auto-injector. A hand-held auto-injector is pocket-sized and can be used in non-medical settings such as in the home. It is designed for use by laypersons, including family members and caregivers of opioid users at risk for an opioid emergency, such as an overdose.{{cite press release |url=https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm391465.htm|title=FDA approves new hand-held auto-injector to reverse opioid overdose |publisher = U.S. Food and Drug Administration (FDA) |archive-url= https://web.archive.org/web/20150716003000/https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm391465.htm|archive-date=16 July 2015|access-date=20 July 2015|url-status=dead}} According to the FDA's National Drug Code Directory, a generic version of the auto-injector began to be marketed at the end of 2019.{{cite web|url=https://ndclist.com/ndc/72853-051/package/72853-051-02|title=NDC 72853-051-02 Naloxone Hydrochloride Auto-injector|website=NDClist.com|access-date=21 March 2020|archive-date=21 March 2020|archive-url=https://web.archive.org/web/20200321212308/https://ndclist.com/ndc/72853-051/package/72853-051-02|url-status=dead}}

Narcan nasal spray was approved in the US in 2015 and is the first FDA-approved nasal spray for emergency treatment or suspected overdose.{{cite press release|url=https://www.fda.gov/news-events/press-announcements/fda-approves-first-generic-naloxone-nasal-spray-treat-opioid-overdose|title=FDA approves first generic naloxone nasal spray to treat opioid overdose|date=11 September 2019|publisher=U.S. Food and Drug Administration (FDA)|access-date=23 October 2019|archive-date=14 September 2019|archive-url=https://web.archive.org/web/20190914122901/https://www.fda.gov/news-events/press-announcements/fda-approves-first-generic-naloxone-nasal-spray-treat-opioid-overdose|url-status=dead}}{{cite web |title = FDA Approves Narcan Nasal Spray|url = http://www.jems.com/articles/2015/11/fda-approves-narcan-nasal-spray.html|website = www.jems.com|access-date = 21 November 2015|url-status = live|archive-url = https://web.archive.org/web/20151120184918/http://www.jems.com/articles/2015/11/fda-approves-narcan-nasal-spray.html|archive-date = 20 November 2015}} It was developed in a partnership between LightLake Therapeutics and the National Institute on Drug Abuse.{{cite web |url=https://www.drugabuse.gov/about-nida/noras-blog/2015/11/narcan-nasal-spray-life-saving-science-nida|title=Narcan Nasal Spray: Life Saving Science at NIDA| vauthors = Volkow N |date=18 November 2015|website=National Institute on Drug Abuse (NIDA) |url-status=live|archive-url=https://web.archive.org/web/20170226133910/https://www.drugabuse.gov/about-nida/noras-blog/2015/11/narcan-nasal-spray-life-saving-science-nida|archive-date=26 February 2017}} The approval process was fast-tracked.{{cite news|url=https://www.washingtonpost.com/national/health-science/fda-approves-device-to-combat-opiod-drug-overdose/2014/04/03/35b69cac-bb3e-11e3-96ae-f2c36d2b1245_story.html|title=FDA approves device to combat opioid drug overdose| vauthors = Dennis B |date=3 April 2014|newspaper=The Washington Post|access-date=8 April 2014|url-status=live|archive-url=https://web.archive.org/web/20140407173215/http://www.washingtonpost.com/national/health-science/fda-approves-device-to-combat-opiod-drug-overdose/2014/04/03/35b69cac-bb3e-11e3-96ae-f2c36d2b1245_story.html|archive-date=7 April 2014}} A generic version of the nasal spray was approved in the United States in 2019, though did not come to market until 2021.

In 2021, the FDA approved Kloxxado, an 8{{nbsp}}mg dose of intranasal naloxone developed by Hikma Pharmaceuticals.{{cite press release |date=11 May 2021 |title=FDA Approves Higher Dosage of Naloxone Nasal Spray to Treat Opioid Overdose |url=https://www.fda.gov/news-events/press-announcements/fda-approves-higher-dosage-naloxone-nasal-spray-treat-opioid-overdose |access-date=21 September 2022 |publisher=U.S. Food and Drug Administration (FDA) |archive-date=1 September 2022 |archive-url=https://web.archive.org/web/20220901084121/https://www.fda.gov/news-events/press-announcements/fda-approves-higher-dosage-naloxone-nasal-spray-treat-opioid-overdose |url-status=dead }} Citing the frequent need for multiple 4{{nbsp}}mg doses of Narcan to successfully reverse overdose, packs of Kloxxado Nasal Spray contain two pre-packaged nasal spray devices, each containing 8{{nbsp}}mg of naloxone.{{cite journal | vauthors = Abdelal R, Raja Banerjee A, Carlberg-Racich S, Darwaza N, Ito D, Shoaff J, Epstein J | title = Real-world study of multiple naloxone administration for opioid overdose reversal among bystanders | journal = Harm Reduction Journal | volume = 19 | issue = 1 | pages = 49 | date = May 2022 | pmid = 35596213 | pmc = 9122081 | doi = 10.1186/s12954-022-00627-3 | doi-access = free }}{{cite web | title=Kloxxado- naloxone hcl spray | website=DailyMed | date=10 May 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ebf0f833-c1c0-487c-8f29-01fa8c61b6cb | access-date=7 January 2023 | archive-date=7 January 2023 | archive-url=https://web.archive.org/web/20230107044215/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ebf0f833-c1c0-487c-8f29-01fa8c61b6cb | url-status=live }}

However, a wedge device (nasal atomizer) can also be attached to a syringe that may also be used to create a mist to deliver the drug to the nasal{{nbsp}}mucosa.{{cite journal | vauthors = Wolfe TR, Bernstone T | title = Intranasal drug delivery: an alternative to intravenous administration in selected emergency cases | journal = Journal of Emergency Nursing | volume = 30 | issue = 2 | pages = 141–147 | date = April 2004 | pmid = 15039670 | doi = 10.1016/j.jen.2004.01.006 }} This is useful near facilities where many overdoses occur that already stock injectors.{{cite web| vauthors = Fiore K |title=On-Label Nasal Naloxone in the Works|url=http://www.medpagetoday.com/PublicHealthPolicy/PublicHealth/52118|website=MedPage Today|access-date=20 July 2015|url-status=live|archive-url=https://web.archive.org/web/20150801184056/http://www.medpagetoday.com/PublicHealthPolicy/PublicHealth/52118|archive-date=1 August 2015|date=13 June 2015}}

File:NARCAN teardown.jpg

Administration of naloxone to somebody who has used opioids may cause rapid-onset opioid withdrawal.{{cite journal |vauthors=Britch SC, Walsh SL |title=Treatment of opioid overdose: current approaches and recent advances |journal=Psychopharmacology (Berl) |volume=239 |issue=7 |pages=2063–2081 |date=July 2022 |pmid=35385972 |pmc=8986509 |doi=10.1007/s00213-022-06125-5 |type=Review}}

Naloxone has little to no effect if opioids are not present.{{Cite web |date=2023-08-29 |title=Opioid overdose |url=https://www.who.int/news-room/fact-sheets/detail/opioid-overdose |access-date=2023-11-17 |website=World Health Organization (WHO) }} In people with opioids in their system, it may cause increased sweating, nausea, restlessness, trembling, vomiting, flushing, and headache, and has in rare cases been associated with heart rhythm changes, seizures, and pulmonary edema.{{cite web |url=https://www.drugs.com/sfx/naloxone-side-effects.html |title=Naloxone Side Effects in Detail |website=Drugs.com |access-date=5 May 2015 |url-status=live |archive-url=https://web.archive.org/web/20150507072325/http://www.drugs.com/sfx/naloxone-side-effects.html |archive-date=7 May 2015 }}{{cite journal | vauthors = Schwartz JA, Koenigsberg MD | title = Naloxone-induced pulmonary edema | journal = Annals of Emergency Medicine | volume = 16 | issue = 11 | pages = 1294–1296 | date = November 1987 | pmid = 3662194 | doi = 10.1016/S0196-0644(87)80244-5 }}

Naloxone has been shown to block the action of pain-lowering endorphins the body produces naturally. These endorphins likely operate on the same opioid receptors that naloxone blocks. It is capable of blocking a placebo pain-lowering response if the placebo is administered together with a hidden or blind injection of naloxone.{{cite journal | vauthors = Sauro MD, Greenberg RP | title = Endogenous opiates and the placebo effect: a meta-analytic review | journal = Journal of Psychosomatic Research | volume = 58 | issue = 2 | pages = 115–120 | date = February 2005 | pmid = 15820838 | doi = 10.1016/j.jpsychores.2004.07.001 }} Other studies have found that placebo alone can activate the body's μ-opioid endorphin system, delivering pain relief by the same receptor mechanism as morphine.{{cite news|url=http://sitn.hms.harvard.edu/flash/2016/just-sugar-pill-placebo-effect-real/|title=More Than Just a Sugar Pill: Why the placebo effect is real - Science in the News|date=14 September 2016|work=Science in the News|access-date=14 November 2017|archive-date=15 November 2017|archive-url=https://web.archive.org/web/20171115015402/http://sitn.hms.harvard.edu/flash/2016/just-sugar-pill-placebo-effect-real/|url-status=live}}{{cite journal | vauthors = Carvalho C, Caetano JM, Cunha L, Rebouta P, Kaptchuk TJ, Kirsch I | title = Open-label placebo treatment in chronic low back pain: a randomized controlled trial | journal = Pain | volume = 157 | issue = 12 | pages = 2766–2772 | date = December 2016 | pmid = 27755279 | pmc = 5113234 | doi = 10.1097/j.pain.0000000000000700 }}

Naloxone should be used with caution in people with cardiovascular disease as well as those who are currently taking medications that could have adverse effects on the cardiovascular system such as causing low blood pressure, fluid accumulation in the lungs (pulmonary edema), and abnormal heart rhythms. There have been reports of abrupt reversals with opioid antagonists leading to pulmonary edema and ventricular fibrillation.{{cite web|url=https://www.uptodate.com/contents/naloxone-drug-information|title=Naloxone: Contraindications|website=UpToDate|access-date=31 October 2017|url-access=subscription|archive-date=20 May 2016|archive-url=https://web.archive.org/web/20160520232432/http://www.uptodate.com/contents/naloxone-drug-information|url-status=live}}

Use of naloxone to treat people who have been using opioids recreationally may cause acute opioid withdrawal with distressing physiological symptoms such as shivering, tachycardia, and nausea; these in turn may lead to aggression and reluctance to receive further treatment.{{cite web |type=Practice guideline |page=181 |url=https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/673978/clinical_guidelines_2017.pdf |date=November 2017 |publisher=Public Health England |title=Drug misuse and dependence: UK guidelines on clinical management }}

Naloxone is a lipophilic compound that acts as a non-selective and competitive opioid receptor antagonist.{{cite book | vauthors = Malenka RC, Nestler EJ, Hyman SE | veditors = Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 190–191, 287 | edition = 2nd | quote= Products of this research include the discovery of lipophilic, small-molecule opioid receptor antagonists, such as naloxone and naltrexone, which have been critical tools for investigating the physiology and behavioral actions of opiates.{{nbsp}}... A competitive antagonist of opiate action (naloxone) had been identified in early studies.{{nbsp}}... Opiate antagonists have clinical utility as well. Naloxone, a nonselective antagonist with a relative affinity of μ > δ > κ, is used to treat heroin and other opiate overdoses.}}{{cite web | title=Narcan- naloxone hydrochloride spray Narcan- naloxone hydrochloride spray | website=DailyMed | date=7 October 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=724df050-5332-4d0a-9a5f-17bf08a547e1 | access-date=12 May 2020 | archive-date=30 January 2016 | archive-url=https://web.archive.org/web/20160130063652/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=724df050-5332-4d0a-9a5f-17bf08a547e1 | url-status=live }} The pharmacologically active isomer of naloxone is (−)-naloxone.{{cite web|title=Naloxone: Summary|url=http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1638|website=IUPHAR/BPS Guide to Pharmacology|publisher=International Union of Basic and Clinical Pharmacology|access-date=15 November 2017|quote=The approved drug naloxone INN-assigned preparation is the (-)-enantiomer.{{nbsp}}... The (+) isomer is inactive at the opioid receptors. Marketed formulations may contain naloxone hydrochloride|archive-date=16 November 2017|archive-url=https://web.archive.org/web/20171116132555/http://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1638|url-status=live}} 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.{{cite web|title=Opioid receptors: Introduction|url=http://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=50|website=IUPHAR/BPS Guide to Pharmacology|publisher=International Union of Basic and Clinical Pharmacology|access-date=15 November 2017|quote=The opioid antagonist, naloxone, which binds to μ, δ and κ receptors (with differing affinities), does not have significant affinity for the ORL1/LC132 receptor. These studies indicate that, from a pharmacological perspective, there are two major branches in the opioid peptide-N/OFQ receptor family: the main branch comprising the μ, δ, and κ receptors, where naloxone acts as an antagonist; and a second branch with the receptor for N/OFQ, which has negligible affinity for naloxone.|archive-date=21 October 2017|archive-url=https://web.archive.org/web/20171021111918/http://www.guidetopharmacology.org/GRAC/FamilyIntroductionForward?familyId=50|url-status=live}}

If naloxone is administered in the absence of concomitant opioid use, no functional pharmacological activity occurs, except the inability of the body to combat pain naturally;{{cite journal | vauthors = Schull J, Kaplan H, O'Brien CP |title=Naloxone can alter experimental pain and mood in humans |journal=Physiological Psychology |date=12 June 1981 |volume=9 |issue=3 |pages=245–250 |doi=10.3758/BF03326970 |url=https://link.springer.com/content/pdf/10.3758/BF03326970.pdf |access-date=3 February 2025}} since pure mu-opioid antagonists like naloxone and naltrexone block the effects of endorphins.{{cite web |title=Naloxone Frequently Asked Questions |url=https://www.yashodahospitals.com/medicine-faqs/naloxone/ |website=Yashoda Hospitals |access-date=3 February 2025}}{{cite web |title=Naloxone Drug Facts |url=https://go.drugbank.com/drugs/DB01183 |website=Go.Drugbank.com |publisher=Drug Bank Online |access-date=3 February 2025}} In contrast to direct opiate agonists, which elicit opiate withdrawal symptoms when discontinued in opiate-tolerant people, no evidence indicates the development of tolerance or dependence on naloxone. The mechanism of action is not completely understood, but studies suggest it functions to produce withdrawal symptoms by competing for opioid receptors within the brain (a competitive antagonist, not a direct agonist), thereby preventing the action of both endogenous and xenobiotic opioids on these receptors without directly producing any effects itself.{{cite web|title=Naloxone Hydrochloride injection, solution|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=8535cc84-ad4a-4d67-8480-fb5a2e3406f8|publisher=DailyMed |access-date=21 April 2014|url-status=live|archive-url=https://web.archive.org/web/20140422232959/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=8535cc84-ad4a-4d67-8480-fb5a2e3406f8|archive-date=22 April 2014}}

A single administration of naloxone at a relatively high dose of 2{{nbsp}}mg by intravenous injection has been found to produce brain MOR blockade of 80% at 5{{nbsp}}minutes, 47% at 2{{nbsp}}hours, 44% at 4{{nbsp}}hours, and 8% at 8{{nbsp}}hours.{{cite book | veditors = Miller PM | title = Biological Research on Addiction | series = Comprehensive Addictive Behaviors and Disorders | volume = 2 | vauthors = Colasanti A, Lingford-Hughes A, Nutt D | chapter = Opioids Neuroimaging | date = 2013 | pages = 675–687 | publisher = Elsevier | doi = 10.1016/B978-0-12-398335-0.00066-2 | isbn = 9780123983350 }} A low dose (2{{nbsp}}μg/kg) produced brain MOR blockade of 42% at 5{{nbsp}}minutes, 36% at 2{{nbsp}}hours, 33% at 4{{nbsp}}hours, and 10% at 8{{nbsp}}hours. Intranasal administration of naloxone via nasal spray has likewise been found to rapidly occupy brain MORs, with peak occupancy occurring at 20{{nbsp}}minutes, peak occupancies of 67% at a dose of 2{{nbsp}}mg and 85% with 4{{nbsp}}mg, and an estimated half-life of occupancy disappearance of approximately 100{{nbsp}}minutes (1.67{{nbsp}}hours).{{cite book | veditors = Dierckx RA, Otte A, De Vries EF, Van Waarde A, Luiten PG | title = PET and SPECT of Neurobiological Systems | vauthors = Waarde AV, Absalom AR, Visser AK, Dierckx RA | chapter = Positron Emission Tomography (PET) Imaging of Opioid Receptors | date = 30 September 2020 | pages = 749–807 | publisher = Springer International Publishing | doi = 10.1007/978-3-030-53176-8_21 | isbn = 978-3-030-53175-1 | s2cid = 241535315 | url = https://research.rug.nl/en/publications/db18f24c-9750-46f6-932d-634dac427c45 | chapter-url = https://research.rug.nl/en/publications/db18f24c-9750-46f6-932d-634dac427c45 | access-date = 23 January 2023 | archive-date = 9 March 2023 | archive-url = https://web.archive.org/web/20230309063205/https://research.rug.nl/en/publications/positron-emission-tomography-pet-imaging-of-opioid-receptors-2 | url-status = live }}{{cite journal | vauthors = Johansson J, Hirvonen J, Lovró Z, Ekblad L, Kaasinen V, Rajasilta O, Helin S, Tuisku J, Sirén S, Pennanen M, Agrawal A, Crystal R, Vainio PJ, Alho H, Scheinin M | title = Intranasal naloxone rapidly occupies brain mu-opioid receptors in human subjects | journal = Neuropsychopharmacology | volume = 44 | issue = 9 | pages = 1667–1673 | date = August 2019 | pmid = 30867551 | pmc = 6785104 | doi = 10.1038/s41386-019-0368-x }}

When administered parenterally (non-orally or non-rectally, e.g., intravenously or by injection), as is most common, naloxone has a rapid distribution throughout the body. The mean serum half-life has been shown to range from 30 to 81 minutes, shorter than the average half-life of some opiates, necessitating repeat dosing if opioid receptors must be stopped from triggering for an extended period. Naloxone is primarily metabolized by the liver. Its major metabolite is naloxone-3-glucuronide, which is excreted in the urine. For people with liver diseases such as alcoholic liver disease or hepatitis, naloxone usage has not been shown to increase serum liver enzyme levels.{{Citation|title=Naloxone|date=2012|url=http://www.ncbi.nlm.nih.gov/books/NBK548244/|work=LiverTox: Clinical and Research Information on Drug-Induced Liver Injury|publisher=National Institute of Diabetes and Digestive and Kidney Diseases|pmid=31643568|access-date=30 October 2019|archive-date=28 August 2021|archive-url=https://web.archive.org/web/20210828181317/https://www.ncbi.nlm.nih.gov/books/NBK548244/|url-status=live}}

Naloxone has low systemic bioavailability when taken by mouth due to hepatic first-pass metabolism, but it does block opioid receptors that are located in the intestine.{{cite journal | vauthors = Meissner W, Schmidt U, Hartmann M, Kath R, Reinhart K | title = Oral naloxone reverses opioid-associated constipation | journal = Pain | volume = 84 | issue = 1 | pages = 105–109 | date = January 2000 | pmid = 10601678 | doi = 10.1016/S0304-3959(99)00185-2 | s2cid = 42230143 }}

Naloxone, also known as N-allylnoroxymorphone or as 17-allyl-4,5α-epoxy-3,14-dihydroxymorphinan-6-one, is a synthetic morphinan derivative and was derived from oxymorphone (14-hydroxydihydromorphinone), an opioid analgesic.{{cite book| vauthors = Dean R, Bilsky EJ, Negus SS |title=Opiate Receptors and Antagonists: From Bench to Clinic|url=https://books.google.com/books?id=zqj2vy6VFUcC&pg=PA514|date=12 March 2009|publisher=Springer Science & Business Media|isbn=978-1-59745-197-0|pages=514–}}{{cite book| vauthors = Nagase H |title=Chemistry of Opioids|url=https://books.google.com/books?id=eegLBwAAQBAJ&pg=PA93|date=21 January 2011|publisher=Springer|isbn=978-3-642-18107-8|pages=93–}}{{cite web | url=http://webbook.nist.gov/cgi/cbook.cgi?ID=C465656 | title=Morphinan-6-one, 4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-, (5α)- | access-date=20 November 2017 | archive-date=1 December 2017 | archive-url=https://web.archive.org/web/20171201041953/http://webbook.nist.gov/cgi/cbook.cgi?ID=C465656 | url-status=live }} Oxymorphone, in turn, was derived from morphine, an opioid analgesic and naturally occurring constituent of the opium poppy.{{cite book|vauthors=Seppala MD, Rose ME|title=Prescription Painkillers: History, Pharmacology, and Treatment|url=https://books.google.com/books?id=HkXXDQAAQBAJ&pg=PT143|date=25 January 2011|publisher=Hazelden Publishing|isbn=978-1-59285-993-1|pages=143–|access-date=20 November 2017|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113020758/https://books.google.com/books?id=HkXXDQAAQBAJ&pg=PT143|url-status=live}} Naloxone is a racemic mixture of two enantiomers, (–)-naloxone (levonaloxone) and (+)-naloxone (dextronaloxone), only the former of which is active at opioid receptors.{{cite book|vauthors=Bennett LA|title=New Topics in Substance Abuse Treatment|url=https://books.google.com/books?id=aIDGy72xseMC&pg=PA9|year=2006|publisher=Nova Publishers|isbn=978-1-59454-831-4|pages=9–|access-date=20 November 2017|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113020758/https://books.google.com/books?id=aIDGy72xseMC&pg=PA9|url-status=live}}{{cite book|vauthors=Wang JQ|title=Drugs of Abuse: Neurological Reviews and Protocols|url=https://books.google.com/books?id=cuxYNGtzSTIC&pg=PA44|year=2003|publisher=Springer Science & Business Media|isbn=978-1-59259-358-3|pages=44–|access-date=20 November 2017|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113020759/https://books.google.com/books?id=cuxYNGtzSTIC&pg=PA44|url-status=live}} The drug is highly lipophilic, allowing it to rapidly penetrate the brain and to achieve a far greater brain to serum ratio than that of morphine. Opioid antagonists related to naloxone include cyprodime, nalmefene, nalodeine, naloxol, and naltrexone.{{cite book|vauthors=Brunton L, Chabner B, Knollman B|title=Goodman and Gilman's The Pharmacological Basis of Therapeutics, Twelfth Edition|url=https://books.google.com/books?id=bVUfAQAAQBAJ|date=20 December 2010|publisher=McGraw Hill Professional|isbn=978-0-07-162442-8|page=510|access-date=20 November 2017|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113020759/https://books.google.com/books?id=bVUfAQAAQBAJ|url-status=live}}

Naloxone was patented in 1961 by Mozes J. Lewenstein, Jack Fishman, and the company Sankyo. It was approved for opioid use disorder treatment in the United States in 1971.{{cite web | title=Naloxone: FDA-Approved Drugs | publisher=U.S. Food and Drug Administration (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=016636 | access-date=13 May 2020 | archive-date=4 August 2020 | archive-url=https://web.archive.org/web/20200804041436/https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=016636 | url-status=live }}

Naloxone has been subject to much inaccurate media reporting and many urban legends about it have become prevalent.{{cite journal |vauthors=Crabtree A, Masuda JR |title=Naloxone urban legends and the opioid crisis: what is the role of public health? |journal=BMC Public Health |volume=19 |issue=1 |pages=670 |date=May 2019 |pmid=31146721 |pmc=6543555 |doi=10.1186/s12889-019-7033-5 |url= |doi-access=free }}

One such myth is that naloxone makes the recipient violent.{{cite web |publisher=Indiana State Department of Health |url=https://www.in.gov/health/overdose-prevention/files/47_naloxone-myths-debunked.pdf |type=pdf |title=Naloxone myths debunked |accessdate=7 September 2023}} Another is that events called "Lazarus parties" have taken place, in which people reportedly took fatal overdoses in anticipation of being treated with naloxone; in reality this was a fiction spread by the police. Yet another is the claim that people have indulged in "yo-yoing", whereby they would take naloxone and opioids simultaneously to enjoy an extreme "high" and subsequent revival; the idea is scientifically nonsensical.

Naloxone is its international nonproprietary name, British Approved Name, Dénomination Commune Française, Denominazione Comune Italiana, and Japanese Accepted Name, while naloxone hydrochloride is its United States Adopted Name and British Approved Name (Modified).{{cite book|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA851|title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|vauthors=Elks J|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=851–|access-date=20 November 2017|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113020759/https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA851|url-status=live}}{{cite book|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA715|title=Index Nominum 2000: International Drug Directory|publisher=Taylor & Francis|year=2000|isbn=978-3-88763-075-1|pages=715–|access-date=20 November 2017|archive-date=13 January 2023|archive-url=https://web.archive.org/web/20230113020800/https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA715|url-status=live}}{{cite book|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA189|title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms| vauthors = Morton IK, Hall JM |date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=189–}}{{cite web|url=https://www.drugs.com/international/naloxone.html|title=Naloxone|access-date=20 November 2017|archive-date=1 December 2017|archive-url=https://web.archive.org/web/20171201044530/https://www.drugs.com/international/naloxone.html|url-status=live}}

The patent has expired and it is available as a generic medication. Several formulations use patented dispensers (spray mechanisms or autoinjectors), and patent disputes over the generic forms of the nasal spray were litigated between 2016 and 2020 when a judge ruled in favor of Teva, the generic manufacturer.{{cite web|title=Teva Invalidates Opiant Patents In Narcan Suit - Law360|url=https://www.law360.com/articles/1280639/teva-invalidates-opiant-patents-in-narcan-suit|access-date=5 January 2022|website=www.law360.com|archive-date=7 January 2022|archive-url=https://web.archive.org/web/20220107035328/https://www.law360.com/articles/1280639/teva-invalidates-opiant-patents-in-narcan-suit|url-status=live}} Teva announced entry of the first generic nasal spray formulation in December 2021.{{cite press release | title=Teva Announces Launch of First-to-Market Generic Version of Narcan (Naloxone Hydrochloride Nasal Spray), in the U.S. | publisher=Teva Pharmaceuticals | via=Business Wire | date=22 December 2021 | url=https://www.businesswire.com/news/home/20211222005564/en/ | access-date=2 August 2023}} Brand names of naloxone include Narcan, Kloxxado, Nalone, Evzio, Prenoxad Injection, Narcanti, Narcotan, and Zimhi, among others.

{{Globalize|date=September 2022|2=US|3=Canada|talk=Talk:Naloxone#North-America-centric_legal_status_section|section}}

Naloxone (Nyxoid) was approved for use in the European Union in September 2017.{{cite web | title=Nyxoid EPAR | website=European Medicines Agency (EMA) | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/nyxoid | access-date=12 May 2020 | archive-date=5 April 2020 | archive-url=https://web.archive.org/web/20200405084842/https://www.ema.europa.eu/en/medicines/human/EPAR/nyxoid | url-status=live }}

In the United States, some nasal naloxone are legally available without a prescription.{{cite news|url=https://www.wyomingnews.com/news/local_news/wyoming-s-albertsons-safeway-pharmacies-to-offer-narcan-over-the/article_ca4b259c-08ae-11e8-9f50-17a75174a10d.html|title=Wyoming's Albertsons, Safeway pharmacies to offer Narcan over the counter|vauthors=Suttles C|work=Wyoming Tribune Eagle|access-date=19 September 2018|archive-date=3 February 2018|archive-url=https://web.archive.org/web/20180203160745/https://www.wyomingnews.com/news/local_news/wyoming-s-albertsons-safeway-pharmacies-to-offer-narcan-over-the/article_ca4b259c-08ae-11e8-9f50-17a75174a10d.html|url-status=live}}{{Cite web | vauthors = Kekatos M |date=May 15, 2024 |title=Walgreens announces it will sell generic version of over-the-counter Narcan |url=https://abcnews.go.com/Health/walgreens-announces-sell-generic-version-counter-narcan/story?id=110258916 |access-date=2024-08-10 |website=ABC News }}

As of 2019, officials in 29 states had issued standing orders to enable licensed pharmacists to provide naloxone to patients without the individual first visiting a prescriber.{{cite web|title=Addressing Opioid Overdose through Statewide Standing Orders for Naloxone Distribution|url=https://www.networkforphl.org/news-insights/addressing-opioid-overdose-through-statewide-standing-orders-for-naloxone-distribution/|access-date=5 January 2022|website=Network for Public Health Law|archive-date=6 January 2022|archive-url=https://web.archive.org/web/20220106000240/https://www.networkforphl.org/news-insights/addressing-opioid-overdose-through-statewide-standing-orders-for-naloxone-distribution/|url-status=live}} Prescribers working with harm reduction or low threshold treatment programs have also issued standing orders to enable these organizations to distribute naloxone to their clients.{{cite journal | vauthors = Wheeler E, Jones TS, Gilbert MK, Davidson PJ | title = Opioid Overdose Prevention Programs Providing Naloxone to Laypersons - United States, 2014 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 64 | issue = 23 | pages = 631–635 | date = June 2015 | pmid = 26086633 | pmc = 4584734 }} A standing order, also referred to as a "non-patient specific prescription" is written by a physician, nurse or other prescriber to authorize medicine distribution outside the doctor-patient relationship.{{cite web |title=Guide: Treating Heroin and Opioid Use Disorder |url=https://www.pa.gov/guides/opioid-epidemic/ |access-date=1 October 2020 |publisher=PA.Gov |archive-date=1 October 2020 |archive-url=https://web.archive.org/web/20201001131912/https://www.pa.gov/guides/opioid-epidemic/ |url-status=live }} In the case of naloxone, these orders are meant to facilitate naloxone distribution to people using opioids, and their family members and friends. Over 200 naloxone distribution programs utilize licensed prescribers to distribute the drug through such orders, or through the authority of pharmacists (as with California's legal provision, AB1535).{{cite report |title=Closing Death's Door: Action Steps to Facilitate Emergency Opioid Drug Overdose Reversal in the United States |year=2009 |url=https://medicine.wright.edu/sites/medicine.wright.edu/files/page/attachments/Naloxonewhitepaper09.pdf |publisher=Boonshoft School of Medicine |archive-url=https://web.archive.org/web/20230127043207/https://medicine.wright.edu/sites/medicine.wright.edu/files/page/attachments/Naloxonewhitepaper09.pdf |archive-date=27 January 2023 |ssrn=1437163 |vauthors=Beletsky L, Burris SC, Kral AH|doi=10.2139/ssrn.1437163 }}{{cite SSRN|title=Stopping an Invisible Epidemic: Legal Issues in the Provision of Naloxone to Prevent Opioid Overdose|year=2009 |ssrn=1434381|vauthors=Burris SC, Beletsky L, Castagna CA, Coyle C, Crowe C, McLaughlin JM}}

Laws and policies in many US jurisdictions have been changed to allow wider distribution of naloxone.{{cite journal|vauthors=Davis C|title=Legal interventions to reduce overdose mortality: Naloxone access and overdose good samaritan laws|url=https://www.networkforphl.org/_asset/qz5pvn/network-naloxone-10-4.pdf|url-status=live|journal=Network for Public Health Law|archive-url=https://web.archive.org/web/20140903114828/https://www.networkforphl.org/_asset/qz5pvn/network-naloxone-10-4.pdf|archive-date=3 September 2014}}{{cite journal | vauthors = Davis C, Webb D, Burris S | title = Changing law from barrier to facilitator of opioid overdose prevention | journal = The Journal of Law, Medicine & Ethics | volume = 41 | issue = Suppl 1 | pages = 33–36 | date = March 2013 | pmid = 23590737 | doi = 10.1111/jlme.12035 | s2cid = 22127036 }} In addition to laws or regulations permitting distribution of medicine to at-risk individuals and families, some 36 states have passed laws that provide naloxone prescribers with immunity against both civil and criminal liabilities.{{cite web | vauthors = Cutcliff A, Stringberg A, Atkins C |title=As Naloxone Accessibility Increases, Pharmacist's Role Expands|url=https://www.pharmacytimes.com/contributor/marilyn-bulloch-pharmd-bcps/2016/10/as-naloxone-accessibility-increases-pharmacists-role-expands|access-date=31 October 2019|website=Pharmacy Times|archive-date=31 October 2019|archive-url=https://web.archive.org/web/20191031180459/https://www.pharmacytimes.com/contributor/marilyn-bulloch-pharmd-bcps/2016/10/as-naloxone-accessibility-increases-pharmacists-role-expands|url-status=dead}} While paramedics in the US have carried naloxone for decades, law enforcement officers in many states throughout the country carry naloxone to reverse the effects of heroin overdoses when reaching the location before paramedics. As of 12 July 2015, law enforcement departments in 28 US states are allowed to or required to carry naloxone to quickly respond to opioid overdoses.{{cite web |url=http://www.nchrc.org/law-enforcement/us-law-enforcement-who-carry-naloxone/ |title=US Law Enforcement Who Carry Naloxone |website=North Carolina Harm Reduction Coalition |access-date=12 July 2015 |url-status=live |archive-url=https://web.archive.org/web/20150713032125/http://www.nchrc.org/law-enforcement/us-law-enforcement-who-carry-naloxone/ |archive-date=13 July 2015 }} Programs training fire personnel in opioid overdose response using naloxone have also shown promise in the US, and efforts to integrate opioid fatality prevention into emergency response have grown due to the US overdose crisis.{{cite journal | vauthors = Beletsky L, Rich JD, Walley AY | title = Prevention of fatal opioid overdose | journal = JAMA | volume = 308 | issue = 18 | pages = 1863–1864 | date = November 2012 | pmid = 23150005 | pmc = 3551246 | doi = 10.1001/jama.2012.14205 }}{{cite journal| vauthors = Lavoie D|date=April 2012|title=Naloxone: Drug-Overdose Antidote Is Put In Addicts' Hands|url=https://www.huffingtonpost.com/2012/04/26/naloxone-drug-overdose-antidote_n_1456531.html|url-status=live|journal=Huffington Post|archive-url=https://web.archive.org/web/20120518161613/http://www.huffingtonpost.com/2012/04/26/naloxone-drug-overdose-antidote_n_1456531.html|archive-date=18 May 2012}}{{cite journal | vauthors = Davis CS, Beletsky L | title = Bundling occupational safety with harm reduction information as a feasible method for improving police receptiveness to syringe access programs: evidence from three U.S. cities | journal = Harm Reduction Journal | volume = 6 | issue = 1 | pages = 16 | date = July 2009 | pmid = 19602236 | pmc = 2716314 | doi = 10.1186/1477-7517-6-16 | doi-access = free }}{{cite report |year=2013|title=2013 National drug control strategy|url=https://obamawhitehouse.archives.gov//sites/default/files/ondcp/policy-and-research/ndcs_2013.pdf|url-status=live|archive-url=https://web.archive.org/web/20170121100239/https://obamawhitehouse.archives.gov/sites/default/files/ondcp/policy-and-research/ndcs_2013.pdf|archive-date=21 January 2017|publisher=Office of National Drug Control Policy }}

Following the use of the nasal spray device by police officers on Staten Island in New York, an additional 20,000 police officers began carrying naloxone in mid-2014. The state's Office of the Attorney General provided US$1.2 million to supply nearly 20,000 kits. Police Commissioner William Bratton said: "Naloxone gives individuals a second chance to get help".{{cite news| vauthors = Durando J |date=27 May 2014|title=NYPD officers to carry heroin antidote|newspaper=USA Today|url=https://www.usatoday.com/story/news/nation-now/2014/05/27/new-york-police-department-naloxone/9630299/|url-status=live|access-date=30 May 2014|archive-url=https://web.archive.org/web/20140703123154/http://www.usatoday.com/story/news/nation-now/2014/05/27/new-york-police-department-naloxone/9630299/|archive-date=3 July 2014}} Emergency Medical Service Providers (EMS) routinely administer naloxone, except where basic Emergency Medical Technicians are prohibited by policy or by state law.{{cite journal | vauthors = Faul M, Dailey MW, Sugerman DE, Sasser SM, Levy B, Paulozzi LJ | title = Disparity in naloxone administration by emergency medical service providers and the burden of drug overdose in US rural communities | journal = American Journal of Public Health | volume = 105 | issue = Suppl 3 | pages = e26–e32 | date = July 2015 | pmid = 25905856 | pmc = 4455515 | doi = 10.2105/AJPH.2014.302520 }} In efforts to encourage citizens to seek help for possible opioid overdoses, many states have adopted Good Samaritan laws that provide immunity against certain criminal liabilities for anybody who, in good faith, seeks emergency medical care for either themselves or someone around them who may be experiencing an opioid overdose.{{cite web|title=Drug Overdose Immunity and Good Samaritan Laws|url=http://www.ncsl.org/research/civil-and-criminal-justice/drug-overdose-immunity-good-samaritan-laws.aspx|access-date=31 October 2019|website=www.ncsl.org|archive-date=13 September 2019|archive-url=https://web.archive.org/web/20190913233059/http://www.ncsl.org/research/civil-and-criminal-justice/drug-overdose-immunity-good-samaritan-laws.aspx|url-status=live}}

States including Vermont and Virginia have developed programs that mandate the prescription of naloxone when a prescription has exceeded a certain level of morphine milliequivalents per day as preventative measures against overdose.{{cite journal | vauthors = Jones CM, Compton W, Vythilingam M, Giroir B | title = Naloxone Co-prescribing to Patients Receiving Prescription Opioids in the Medicare Part D Program, United States, 2016-2017 | journal = JAMA | volume = 322 | issue = 5 | pages = 462–464 | date = August 2019 | pmid = 31386124 | pmc = 6686765 | doi = 10.1001/jama.2019.7988 }} Healthcare institution-based naloxone prescription programs have also helped reduce rates of opioid overdose in North Carolina, and have been replicated in the US military.{{cite journal | vauthors = Albert S, Brason FW, Sanford CK, Dasgupta N, Graham J, Lovette B | title = Project Lazarus: community-based overdose prevention in rural North Carolina | journal = Pain Medicine | volume = 12 | issue = Suppl 2 | pages = S77–S85 | date = June 2011 | pmid = 21668761 | doi = 10.1111/j.1526-4637.2011.01128.x | doi-access = free | title-link = doi }}

In Canada, naloxone single-use syringe kits are distributed and available at various clinics and emergency rooms. Alberta Health Services is increasing the distribution points for naloxone kits at all emergency rooms, and various pharmacies and clinics province-wide. All Edmonton Police Service and Calgary Police Service patrol cars carry an emergency single-use naloxone syringe kit. Some Royal Canadian Mounted Police patrol vehicles also carry the drug, occasionally in excess to help distribute naloxone among users and concerned family/friends. Nurses, paramedics, medical technicians, and emergency medical responders can also prescribe and distribute the drug. As of February 2016, pharmacies across Alberta and some other Canadian jurisdictions are allowed to distribute single-use take-home naloxone kits or prescribe the drug to people using opioids.

Following Alberta Health Services, Health Canada reviewed the prescription-only status of naloxone, resulting in plans to remove it in 2016, making naloxone more accessible.{{cite news |url=https://www.cbc.ca/news/health/naloxone-s-prescription-only-status-to-get-health-canada-review-1.3166867 |title=Naloxone's prescription-only status to get Health Canada review |website=CBC News |access-date=5 February 2016 |url-status=live |archive-url=https://web.archive.org/web/20160205205030/https://www.cbc.ca/news/health/naloxone-s-prescription-only-status-to-get-health-canada-review-1.3166867 |archive-date=5 February 2016 }}{{cite web |url=http://www.health.alberta.ca/health-info/AMH-Naloxone-Take-home.html |title=Fentanyl and the take-home naloxone program Alberta Health |access-date=5 February 2016 |url-status=dead |archive-url=https://web.archive.org/web/20160205142858/http://www.health.alberta.ca/health-info/AMH-Naloxone-Take-home.html |archive-date=5 February 2016 }} Due to the rising number of drug deaths across the country, Health Canada proposed a change to make naloxone more widely available to Canadians in support of efforts to address the growing number of opioid overdoses.{{cite press release | title=Health Canada Statement on Change in Federal Prescription Status of Naloxone | publisher=Health Canada | date=14 January 2016 | url=https://www.canada.ca/en/health-canada/news/2016/01/health-canada-statement-on-change-in-federal-prescription-status-of-naloxone.html | access-date=6 October 2024}} In March 2016, Health Canada did change the prescription status of naloxone, as "pharmacies are now able to proactively give out naloxone to those who might experience or witness an opioid overdose."{{cite web |url=http://www.hc-sc.gc.ca/dhp-mps/prodpharma/pdl-ord/pdl-ldo-qa-naloxone-qr-eng.php |title=Questions and Answers - Naloxone |website=Health Canada |date=22 March 2017 |access-date=12 June 2017 |url-status=live |archive-url=https://web.archive.org/web/20170908140357/http://www.hc-sc.gc.ca/dhp-mps/prodpharma/pdl-ord/pdl-ldo-qa-naloxone-qr-eng.php |archive-date=8 September 2017 }}

File:Mendocino Pride 2023 - Sarah Stierch - 12.jpg.]]In a survey of US laypersons in December 2021, most people believed the scientifically supported idea that trained bystanders can reverse overdoses with naloxone.{{cite journal | vauthors = Agley J, Xiao Y, Eldridge L, Meyerson B, Golzarri-Arroyo L | title = Beliefs and misperceptions about naloxone and overdose among U.S. laypersons: a cross-sectional study | journal = BMC Public Health | volume = 22 | issue = 1 | pages = 924 | date = May 2022 | pmid = 35538566 | pmc = 9086153 | doi = 10.1186/s12889-022-13298-3 | doi-access = free }}

A survey of US naloxone prescription programs in 2010 revealed that 21 out of 48 programs reported challenges in obtaining naloxone in the months leading up to the survey, due mainly to either cost increases that outstripped allocated funding or the suppliers' inability to fill orders. The approximate cost of a 1{{nbsp}}ml ampoule of naloxone in the US is estimated to be significantly higher than in most other countries.

Take-home naloxone programs for people who use opioids are underway in many North American cities.{{cite journal | title = Community-based opioid overdose prevention programs providing naloxone - United States, 2010 | journal = MMWR. Morbidity and Mortality Weekly Report | volume = 61 | issue = 6 | pages = 101–105 | date = February 2012 | pmid = 22337174 | pmc = 4378715 | url = https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6106a1.htm | url-status = live | archive-url = https://web.archive.org/web/20120426204807/http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6106a1.htm | archive-date = 26 April 2012 | author1 = Centers for Disease Control Prevention (CDC) }}{{cite web |url=https://www.thestar.com/news/gta/2012/09/09/toronto_naloxone_program_reduces_drug_overdoses_among_addicts.html |title=Toronto naloxone program reduces drug overdoses among addicts |newspaper=The Toronto Star |date=9 September 2012 | vauthors = Donkin K |access-date=5 May 2015 |url-status=live |archive-url=https://web.archive.org/web/20141205045540/http://www.thestar.com/news/gta/2012/09/09/toronto_naloxone_program_reduces_drug_overdoses_among_addicts.html |archive-date=5 December 2014 }} CDC estimates that the US programs for drug users and their caregivers prescribing take-home doses of naloxone and training on its use prevented 10,000 opioid overdose deaths by 2014.

In Australia, some forms of naloxone are available "over the counter" in pharmacies free without a prescription under the Take Home Naloxone programme.{{cite journal | vauthors = Lenton SR, Dietze PM, Jauncey M | title = Australia reschedules naloxone for opioid overdose | journal = The Medical Journal of Australia | volume = 204 | issue = 4 | pages = 146–147 | date = March 2016 | pmid = 26937664 | doi = 10.5694/mja15.01181 | url = https://www.mja.com.au/journal/2016/204/4/australia-reschedules-naloxone-opioid-overdose | access-date = 19 July 2020 | s2cid = 9320372 | archive-date = 19 July 2020 | archive-url = https://web.archive.org/web/20200719232637/https://www.mja.com.au/journal/2016/204/4/australia-reschedules-naloxone-opioid-overdose | url-status = live | url-access = subscription }}{{cite news| vauthors = Davey M |date=29 January 2016|title=Selling opioid overdose antidote Naloxone over counter 'will save lives'|newspaper=The Guardian|url=https://www.theguardian.com/society/2016/jan/29/selling-opioid-overdose-antidote-naloxone-over-counter-will-save-lives|url-status=live|archive-url= https://web.archive.org/web/20161203055245/https://www.theguardian.com/society/2016/jan/29/selling-opioid-overdose-antidote-naloxone-over-counter-will-save-lives|archive-date=3 December 2016}}{{cite web|date=1 February 2016|title=Why the 'heroin antidote' naloxone is now available in pharmacies|url=http://www.abc.net.au/triplej/programs/hack/how-painkiller-use-becomes-a-heroin-addiction/7129964|url-status=live|archive-url=https://web.archive.org/web/20160204040604/http://www.abc.net.au/triplej/programs/hack/how-painkiller-use-becomes-a-heroin-addiction/7129964|archive-date=4 February 2016|access-date=1 February 2016|work=ABC}} It comes in single-use filled syringe form similar to law enforcement kits as well as nasal sprays. In 2024, those with a prescription can purchase five doses for around AU$32 or just over AU$6 per dose.{{cite web|vauthors=Coulter E|date=27 August 2019|title=This drug can temporarily reverse an opioid overdose. So why aren't people using it?|url=https://www.abc.net.au/news/2019-08-27/naloxone-can-stop-an-overdose-why-arent-people-using-it/11448540|access-date=28 August 2019|website=ABC News|archive-date=27 August 2019|archive-url=https://web.archive.org/web/20190827192233/https://www.abc.net.au/news/2019-08-27/naloxone-can-stop-an-overdose-why-arent-people-using-it/11448540|url-status=live}}{{Cite web | work = Pharmaceutical Benefit Scheme |title=PBS.gov.au {{!}} Naloxone |url=https://m.pbs.gov.au/search.html?term=NALOXONE&analyse=false |access-date=2024-10-30 | publisher = Government of Australia }}

In Alberta, in addition to pharmacy distribution, take-home naloxone kits are available and distributed in most drug treatment or rehabilitation centers.{{cite web | title=Naloxone kits now available at drug stores as province battles fentanyl crisis | website=CBC News | date=17 February 2016 | url=https://www.cbc.ca/news/canada/calgary/naloxone-kits-fentanyl-overdose-province-1.3451860 | access-date=9 March 2023 | archive-url=https://web.archive.org/web/20160304141621/http://www.cbc.ca/news/canada/calgary/naloxone-kits-fentanyl-overdose-province-1.3451860 |archive-date=4 March 2016 | url-status = live }}

In the European Union, take home naloxone pilots were launched in the Channel Islands and in Berlin in the late 1990s.{{cite journal | vauthors = Dettmer K, Saunders B, Strang J | title = Take home naloxone and the prevention of deaths from opiate overdose: two pilot schemes | journal = BMJ | volume = 322 | issue = 7291 | pages = 895–896 | date = April 2001 | pmid = 11302902 | doi = 10.1136/bmj.322.7291.895 | pmc = 30585 }} In 2008, the Welsh Assembly government announced its intention to establish demonstration sites for take-home naloxone,{{cite web|title=IHRA 21st International Conference Liverpool, 26th April 2010 - Introducing 'take home' Naloxone in Wales|url=http://www.ihra.net/files/2010/08/26/Danny_Morris.pdf|url-status=live|archive-url=https://web.archive.org/web/20110720062721/http://www.ihra.net/files/2010/08/26/Danny_Morris.pdf|archive-date=20 July 2011|access-date=9 March 2011}} and in 2010, Scotland instituted a national naloxone program.{{cite journal|vauthors=McAuley A, Best D, Taylor A, Hunter C, Robertson R|date=1 August 2012|title=From evidence to policy: The Scottish national naloxone programme|url=https://doi.org/10.3109/09687637.2012.682232|journal=Drugs: Education, Prevention and Policy|volume=19|issue=4|pages=309–319|doi=10.3109/09687637.2012.682232|s2cid=73263293|issn=0968-7637|access-date=6 January 2022|archive-date=9 March 2023|archive-url=https://web.archive.org/web/20230309063059/https://www.tandfonline.com/doi/full/10.3109/09687637.2012.682232?cookieSet=1|url-status=live|url-access=subscription}} Inspired by North American and European efforts, non-governmental organizations running programs to train drug users as overdose responders and supply them with naloxone are now operational in Russia, Ukraine, Georgia, Kazakhstan, Tajikistan, Afghanistan, China, Vietnam, and Thailand.{{cite web|url=https://www.opensocietyfoundations.org/publications/stopping-overdose|title=Stopping Overdose|publisher=Open Society Foundations|access-date=6 January 2022|archive-date=7 January 2022|archive-url=https://web.archive.org/web/20220107035410/https://www.opensocietyfoundations.org/publications/stopping-overdose|url-status=live}}

In 2018, a maker{{Which|date=January 2025}} of naloxone announced it would provide a free kit including two doses of the nasal spray, as well as educational materials, to each of the 16,568 public libraries and 2,700 YMCAs in the U.S.{{cite magazine |title=Every U.S. Public Library and YMCA Will Soon Get Narcan for Free |url=https://time.com/5432950/narcan-libraries-ymca/ |magazine=Time |access-date=2 April 2019 |archive-date=1 April 2019 |archive-url=https://web.archive.org/web/20190401224345/http://time.com/5432950/narcan-libraries-ymca/ |url-status=live }}

In 2025, an American start-up released a keychain case to make naloxone more immediately accessible in emergencies.{{Cite web |last=Wyman |first=Hannah |date=2025-05-16 |title=Narcan can stop an opioid overdose. A St. Louis couple put it on an easy-to-carry keychain. |url=https://www.stltoday.com/news/local/business/article_9715482a-c301-46e9-837c-c8f42b8811fc.html |access-date=2025-05-16 |website=STLtoday.com |language=en}}

In April 2025, the city of Nashville, Tennessee introduced its first naloxone vending machine at a Twice Daily gas station on West End Avenue. This initiative, a collaboration between the Metro Nashville Health Department, Fund Recovery, and Twice Daily, aims to provide free access to naloxone, an opioid overdose-reversing medication. Within five weeks of installation, the machine dispensed over 2,200 doses, significantly surpassing initial expectations. Encouraged by this success, the health department plans to install three additional machines across Davidson County within 90 days, targeting areas with the highest overdose rates. The program is funded by opioid settlement money and underscores the importance of community partnerships in expanding access to life-saving interventions.{{Cite web |date=2025-05-22 |title=Nashville's free naloxone vending machine dispenses over 2,200 doses in just five weeks |url=https://www.newschannel5.com/news/nashvilles-free-naloxone-vending-machine-dispenses-over-2-200-doses-in-just-five-weeks |access-date=2025-05-24 |website=News Channel 5 Nashville (WTVF) |language=en}}

Naloxone is used to reverse pure μ-opioid receptor agonists and for opioid reversal during cardiopulmonary arrest in cats and dogs. This is often given intravenously but instranasal administration works in the dog at higher doses. Renarcotisation can occur with naloxone administration, especially with morphinans.{{cite book|isbn=978-1-119-83027-6|title=Veterinary Anesthesia and Analgesia, The 6th Edition of Lumb and Jones|editor-first1=Leigh|editor-last1=Lamont|editor-first2=Kurt|editor-last2=Grimm|editor-first3=Sheilah|editor-last3=Robertson|editor-first4=Lydia|editor-last4=Love|editor-first5=Carrie|editor-last5=Schroeder|chapter=Opioids|first1=Bradley T.|last1=Simon|first2=Ignacio|last2=Lizarraga|page=384|publisher=Wiley Blackwell}} Naxlone administration has been reported to result in altered mental status and blepharospasm.{{cite journal | last=Rzasa Lynn | first=Rachael | last2=Galinkin | first2=Jl | title=Naloxone dosage for opioid reversal: current evidence and clinical implications | journal=Therapeutic Advances in Drug Safety | volume=9 | issue=1 | date=2018 | issn=2042-0986 | pmid=29318006 | pmc=5753997 | doi=10.1177/2042098617744161 | doi-access=free | pages=63–88 | url=https://journals.sagepub.com/doi/pdf/10.1177/2042098617744161}}{{cite journal | last=Rzasa Lynn | first=Rachael | last2=Galinkin | first2=Jl | title=Naloxone dosage for opioid reversal: current evidence and clinical implications | journal=Therapeutic Advances in Drug Safety | volume=9 | issue=1 | date=2018 | issn=2042-0986 | pmid=29318006 | pmc=5753997 | doi=10.1177/2042098617744161 | doi-access=free | pages=63–88 | url=https://journals.sagepub.com/doi/pdf/10.1177/2042098617744161}} Aetiology of this is unknown but could be due to either withdrawal, systemic hypertension, or rapid changes to the cerebral vascular tone. One study in horses reported that naloxone administration reduced increases in right ventricular pressure and heart rate caused by endotoxic shock.{{cite journal | last=JM | first=Weld | last2=SG | first2=Kamerling | last3=JD | first3=Combie | last4=TE | first4=Nugent | last5=WE | first5=Woods | last6=P | first6=Oeltgen | last7=T | first7=Tobin | title=The effects of naloxone on endotoxic and hemorrhagic shock in horses | journal=Research communications in chemical pathology and pharmacology | publisher=Res Commun Chem Pathol Pharmacol | volume=44 | issue=2 | issn=0034-5164 | pmid=6739953}}

{{Reflist}}

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• {{cite book | title=Naloxone, Flumazenil and Dantrolene as Antidotes | publisher=Cambridge University Press | year=1993 | url=http://www.inchem.org/documents/antidote/antidote/ant01.htm | volume=1 | id=EUR 14797 EN | isbn=0-521-45459-X | series=IPCS/CEC Evaluation of Antidotes Series | access-date=15 February 2004 | archive-date=15 December 2003 | archive-url=https://web.archive.org/web/20031215213521/http://inchem.org/documents/antidote/antidote/ant01.htm | url-status=live }}

{{refend}}

• {{cite web | title=Naloxone Nasal Spray | publisher=MedlinePlus | url=https://medlineplus.gov/druginfo/meds/a616003.html }}
• {{cite web | title= Opioid Overdose Reversal Medications (OORM) | website=U.S. Substance Abuse and Mental Health Services Administration (SAMHSA | date=26 March 2024 | url=https://www.samhsa.gov/medications-substance-use-disorders/medications-counseling-related-conditions/opioid-overdose-reversal-medications }}

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