[15] Administration to opioid-dependent individuals may cause symptoms of opioid withdrawal, including restlessness, agitation, nausea, vomiting, a fast heart rate, and sweating.

[23] Prescribing naloxone should be accompanied by standard education that includes preventing, identifying, and responding to an overdose; rescue breathing; and calling emergency services.

[25] 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.

[28] 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.

[13][30] 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.

For children with low blood pressure due to septic shock, naloxone safety and effectiveness are not established.

However, older people often have decreased liver and kidney function which may lead to an increased level of naloxone in their body.

[40] 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.

[52] 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.

[55] 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.

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.

[75] 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.

[77][78][79] Oxymorphone, in turn, was derived from morphine, an opioid analgesic and naturally occurring constituent of the opium poppy.

[86] 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.

[85] 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.

[46] Brand names of naloxone include Narcan, Kloxxado, Nalone, Evzio, Prenoxad Injection, Narcanti, Narcotan, and Zimhi, among others.

[93][94] 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.

[95] 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.

[96] 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.

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.

[111] 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.

Alberta Health Services is increasing the distribution points for naloxone kits at all emergency rooms, and various pharmacies and clinics province-wide.

Some Royal Canadian Mounted Police patrol vehicles also carry the drug, occasionally in excess to help distribute naloxone among users and concerned family/friends.

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.

"[117] In a survey of US laypersons in December 2021, most people believed the scientifically supported idea that trained bystanders can reverse overdoses with naloxone.

[119][120] 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.

[113] In the European Union, take home naloxone pilots were launched in the Channel Islands and in Berlin in the late 1990s.

[127] 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.

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.[129]