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How Opioid Antagonists Work

Published on March 5, 2021
How Opioid Antagonists Work | Naloxone & Naltrexone

An opioid antagonist is a substance that blocks or reverses the effects of opioids. They are often given to patients suffering from a life-threatening opioid overdose, or to manage opioid withdrawal symptoms.

Opioid antagonists affect the same parts of the brain as opioids, but have different effects.

How Opioid Antagonists Affect The Brain

Opioid receptor antagonists (or simply opioid antagonists) bind to opioid receptors in the central nervous system, including the brain. They bind to specific receptors known as kappa or mu receptors, depending on the type of antagonist used.

Opioids also bind to opioid receptors, but how they affect the body is generally different.

Opioids vs. Opioid Agonists vs. Opioid Antagonists

An agonist is any drug that activates receptors in the brain. They are separated into partial agonists and full agonists. Partial agonists do not affect receptors in the brain as strongly as full agonists do.

When opioids bind to opioid receptors, they cause numbing or analgesic effects. Popular opioid drugs that cause these effects include oxycodone, hydrocodone, codeine, and fentanyl. These drugs can help with chronic pain and pain management, but can also come with many side effects.

Opioid antagonists have opposite effects to opioids.  Antagonists increase breathing activity, reduce analgesia (numbing), and reduce sedation.

Types Of Opioid Antagonists

Naltrexone, naloxone, and nalbuphine are some well-known opioid antagonists. They are usually prescribed for different reasons.


Naloxone can treat opiate and opioid overdoses, which often cause severe respiratory depression (extremely slowed breathing). It is available as a nasal spray and as an intravenous injectable formulation. Naloxone can save a person’s life by restoring normal breathing.

When combined with buprenorphine (a partial opioid agonist), naloxone can also treat withdrawal symptoms and reduce cravings. Prescriptions for these naloxone/buprenorphine combinations include Suboxone and Zubsolv.

As of 2020, healthcare professionals who are prescribing opioids should also recommend naloxone 


Naltrexone may be prescribed as a part of medication-assisted treatment (MAT) for opioid withdrawal. It can reduce opioid cravings and reduce the chances of a relapse. Vivitrol is one commonly prescribed brand of naltrexone.

Naltrexone can be prescribed along with buprenorphine. Medication-assisted treatment may be more effective when combined with other treatment services, such as therapy or counseling.


Nalbuphine is not a true opioid antagonist. It is classified as a partial agonist, or an opioid agonist/antagonist. On its own, it can cause numbing and sedation similar to actual opioids. 

Nalbuphine is usually not prescribed as a treatment for opioid dependence or overdose. However, it can reduce the severity of respiratory depression when combined with other opioids, slightly reducing their risks when taken.

Other Antagonists

Other opioid antagonists may be prescribed for more specific uses. Methylnaltrexone is one such antagonist that can treat opioid-induced constipation. It works by removing opioids from receptors in the stomach, bladder, and skin.

Methadone, which can also treat opioid withdrawal, is not an opioid antagonist. It is itself an opioid, and it may be more addictive than most antagonists.

Are Opioid Antagonists Safe?

All drugs have some sort of risk. Opioid antagonists can make withdrawal symptoms worse in some cases, or even cause withdrawal of their own. 

Compared to the risks of opioid dependence and overdose these antagonists treat, however, opioid antagonists are usually safer even if you do experience side effects. 

If you’re taking an opioid antagonist, your doctor should be managing your dosings to reduce the risks that higher doses bring.

Opioid Use & Addiction

Long-term opiate or opioid use can cause long-term damage to your health. While they can help treat pain, their negative effects can start to outweigh their positive ones, especially in the long-term.

Opioid antagonists can help treat these negative effects, even in the case of an overdose. To learn more about the effects of opioids and how treatment can help, please contact us today.

Written by Ark Behavioral Health Editorial Team
This page does not provide medical advice.

Indian Health Service - Pharmacological Treatment | Medication Assisted Recovery
National Centers for Biotechnology Information - Nalbuphine - StatPearls - NCBI Bookshelf
National Centers for Biotechnology Information - Opioid Antagonists - StatPearls - NCBI Bookshelf
National Institute on Drug Abuse - Opioid Overdose Reversal with Naloxone (Narcan, Evzio) | National Institute on Drug Abuse (NIDA)
National Library of Medicine - Methylnaltrexone | C21H26NO4+ - PubChem
U.S. Food and Drug Administration - New Recommendations for Naloxone | FDA

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