Naloxone

Naloxone (often known by the brand name Narcan) is a medication that works as an opioid antagonist, meaning it blocks the effects of opioids and can reverse or lessen them. Its main use is to restart breathing during an opioid overdose. How quickly it works depends on how it's given: about two minutes if injected into a vein, five minutes if injected into a muscle, and ten minutes if sprayed into the nose (some sources note a 3–7 minute onset for the nasal spray). Once administered, naloxone keeps opioids from working for 30 to 90 minutes.

Giving naloxone to someone who is dependent on opioids can trigger withdrawal symptoms, such as restlessness, agitation, nausea, vomiting, a fast heart rate, and sweating. To avoid this, small doses can be given every few minutes until the overdose is reversed. People with existing heart disease or those on heart-affecting medications may face additional heart problems. There isn't much data on naloxone's safety during pregnancy. The drug works by non-selectively and competitively blocking opioid receptors, which reverses the depression of the central nervous system and breathing caused by opioids.

Naloxone was patented in 1961 and approved in the United States for opioid overdose in 1971. It is listed on the World Health Organization's List of Essential Medicines and is available over the counter.

**Medical uses**

**Opioid overdose** Naloxone is effective for treating both acute opioid overdose and the slowed breathing or mental depression that opioids cause. It's unclear if it helps in cases of cardiac arrest from an overdose. It's included in emergency overdose kits given to users of heroin, fentanyl, and other opioids, as well as to first responders—this has been shown to lower overdose death rates. A prescription for naloxone is recommended for people on high opioid doses (over 100 mg morphine equivalent per day), those taking any opioid with a benzodiazepine, or those suspected of using opioids non-medically. Prescribing should come with education on preventing, identifying, and responding to an overdose, including rescue breathing and calling emergency services. Distributing naloxone to people likely to witness an overdose is part of harm reduction. However, for opioids with longer half-lives, breathing problems can return after naloxone wears off, so ongoing monitoring and repeat dosing may be needed.

**Clonidine overdose** Naloxone can also be used as an antidote for an overdose of clonidine, a blood pressure medication. This is especially important for children, where even small clonidine doses can be dangerous. But its effectiveness for clonidine overdose symptoms—like slow heart rate, low blood pressure, and confusion—is debated. Case reports using doses of 0.1 mg/kg (up to 2 mg per dose) repeated every 1–2 minutes (up to 10 mg total) have shown inconsistent results. Because the doses in studies vary widely, it's hard to draw firm conclusions. The reason naloxone might help in clonidine overdose isn't clear, but it may involve opioid receptors in the brain and body that affect the sympathetic nervous system.

**Preventing recreational opioid use** Naloxone is poorly absorbed when taken by mouth or under the tongue, so it's often added to oral or sublingual opioid preparations (like buprenorphine or pentazocine). When taken as intended, only the opioid has an effect. If the combination is injected (by dissolving a pill or strip), the naloxone is supposed to block the other opioid's effects, discouraging misuse. However, SAMHSA guidelines note that if someone who regularly uses buprenorphine injects a buprenorphine/naloxone combination, the buprenorphine still produces an opioid effect because the amount of naloxone in the pill or strip is too small to block it. For someone not physically dependent on opioids, injecting the combination may slightly lessen the effects, but they would still likely feel euphoria.

**Other uses** A 2003 meta-analysis found that naloxone improved blood flow in patients with shock (septic, cardiogenic, hemorrhagic, or spinal), but it couldn't confirm whether this reduced deaths. Oral naloxone has been tried for opioid-induced constipation. A 2018 meta-analysis reviewed five studies on this, finding that treatment for constipation could be more effective than placebo, but it didn't isolate naloxone's effect, so no conclusion on its specific benefit is possible. Naloxone and other opioid antagonists have been studied for dissociative disorders, based on the idea that these disorders disrupt the body's natural opioid pathways. A 2023 meta-analysis found some evidence they might help, but possible publication bias and differing testing methods mean more research is needed.

**Special populations**

**Pregnancy and breastfeeding** There are no adequate, well-controlled studies on naloxone use in pregnant women. Most information on naloxone in pregnancy comes from limited data.