Opioid antagonists are medications people can take to treat opioid use disorder. They help by reducing withdrawal symptoms, addressing cravings, and managing overdoses.

Doctors prescribe opioid receptor agonist medications to treat chronic pain in some people. These drugs attach to proteins in the brain called opioid receptors, which help block pain signals and send dopamine, a feel-good chemical, through the body.

However, dopamine triggers the brain’s reward system and can be highly addictive, leading an individual to want to take opioids for a “high” feeling rather than pain reduction. Some opiate street drugs, such as heroin and fentanyl, work in the same way.

A class of medications called opioid antagonists can cancel out the effects of opioids and support an individual’s recovery from opioid use disorder in several ways.

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Opioid antagonists are medications that block one or several opioid receptors. Two different types are available, and they vary depending on whether the medication can pass from the blood into the brain, also known as crossing the blood-brain barrier:

  • Centrally acting opioid antagonists: These can readily cross the blood-brain barrier and act directly on receptors in the brain. Naloxone and naltrexone, two of the most commonly prescribed opioid antagonists, act centrally.
  • Peripherally acting opioid antagonist: These act on opioid receptors elsewhere in the body, such as the digestive system and the tubes in the lungs. Methylnaltrexone and nalmefene are two peripherally acting opioid antagonists.

Opioid antagonists work by bonding with opioid receptors in place of opioids. Opioid agonists activate the nerve cells to respond, but antagonists do not trigger a response in the attached cell.

They act as competitive inhibitors, meaning they take the place of the opioid agonists and stop them from reaching the receptor. If an antagonist blocks more receptors, a person feels fewer effects of an opioid. Some antagonists, such as naloxone, act extremely quickly. Others work more slowly to manage opioid use disorder in the long term.

Opioid antagonists bring on precipitated withdrawal, which means that the body rapidly responds to a sudden absence of opioids and quickly causes withdrawal symptoms. According to a 2023 study, this resolves within 2 hours for most people. However, it can be highly uncomfortable.

For this reason, where possible, healthcare professionals provide opioid antagonists in a clinical setting so that they can manage precipitated withdrawal.

Opioid antagonists treat various symptoms of opioid addiction, including the following:

Naloxone

This quickly reverses an opioid overdose and can help a person who has taken too many opioid medications breathe normally if the overdose has affected breathing. Doctors can inject naloxone into the muscle or veins or under the skin. Alternatively, it is available as a nasal spray that untrained family members or bystanders can use instantly in an emergency.

However, naloxone does not treat opioid use disorder in the long term and is only effective for people who have opioids in their system. Naloxone nasal spray is the only option that is currently available over the counter.

Naltrexone

A doctor may prescribe naltrexone along with social support and counseling to help a person continue with recovery in the long term. It can help reduce cravings for opioid drugs or alcohol. People take naltrexone as a pill at home, in a clinic, or at a treatment center.

However, it is only helpful for people who have already stopped taking opioids and does not treat withdrawal symptoms.

Nalmefene

Nalmefene can reverse an opioid overdose. It is available as injections or a nasal spray.

However, according to a 2023 position statement from the American College of Medical Toxicology and the American Academy of Clinical Toxicology, nalmefene bonds with opioid receptors more aggressively than naloxone, and its effects last longer.

A 2021 review maintains that nalmefene could lead to shorter stays in hospital than naloxone for people experiencing an overdose, as it is four times as effective at targeting opioid receptors.

However, the 2023 position statement above argues that nalmefene may lead to longer and more severe periods of precipitated withdrawal than naloxone and should not replace it.

Methylnaltrexone

This is an oral tablet that treats opioid-induced constipation, a common side effect of using opioid pain medications. Methylnaltrexone is a peripheral opioid receptor antagonist that protects receptors in the bowel from the effects of opioids.

People who need methylnaltrexone should take a single pill daily with water around 30 minutes before their first meal of the day. They may also need to stop taking other laxative medications. However, if methylnaltrexone is not effective within 3 days, the prescribing doctor may advise an individual to continue their usual course of laxatives.

Opioid antagonists can save lives, as some can normalize breathing during an overdose. Naloxone and nalmefene can reverse an overdose and are available in a widely usable form, such as a nasal spray. It is a good idea for people living with opioid use disorder and their loved ones to have naloxone or nalmefene nasal spray on hand in case of an emergency.

Naltrexone can block the actions of opioids, helping reduce cravings and assisting with recovery from addiction as part of a long-term program.

Addiction is a complex, multifaceted health problem with physical, psychological, and social factors to consider. Naltrexone can support the physical side of addiction while an individual seeks care around the psychological and social aspects.

The main risk of opioid antagonists is precipitated withdrawal, which causes a rapid onset of withdrawal symptoms, including:

For this reason, precipitated withdrawal must usually occur in a clinical setting to allow for observation. If a person receives naloxone or nalmefene to reverse an overdose in a nonclinical setting, a loved one or bystander should call 911 immediately after giving someone these medications.

Doctors may administer a partial opioid antagonist called buprenorphine along with naloxone to help manage mild to moderate precipitated withdrawal.

Multiple doses of naloxone or nalmefene may be necessary, and they are only effective for people who overdose on opioids. They do not affect those who have taken too much cocaine, methamphetamines, or other illicit drugs.

Some people may have allergic reactions to opioid antagonists.

People with opioid or alcohol use disorders may use opioid antagonists for different reasons. Each antagonist works by blocking opioid receptors and the effects of opioids, opiates, and alcohol. Some act on the brain and central nervous system directly, while others affect receptors in the gut or lungs.

Naloxone and nalmefene can reverse an overdose, naltrexone can reduce cravings as part of long-term recovery management, and methylnaltrexone can treat opioid-induced constipation.

These drugs can bring on a rapid form of withdrawal called precipitated withdrawal, which requires medical supervision. People who use naloxone or nalmefene nasal sprays to treat an overdose outside of a clinical setting should call 911 and wait with the individual until trained help arrives.