Opioid Antagonists: How Naloxone, Naltrexone and Similar Medicines Work
Updated: 6 days ago
Written and medically reviewed by Dr. Baraa Alnahhal, MD · Last reviewed: October 2026 · How we review
Quick Answer: What is an opioid antagonist?
An opioid antagonist is a medicine that attaches to opioid receptors without switching them on, which blocks or reverses the effects of opioids. Naloxone and nalmefene reverse overdoses and restore breathing, naltrexone treats opioid and alcohol use disorder, and methylnaltrexone eases opioid-induced constipation. Given promptly, naloxone can save the life of someone having an opioid overdose. [1][2]
What the research says
Naltrexone helps people with alcohol use disorder avoid drinking again. A review of 118 clinical trials with 20,976 participants found that 18 people needed to take oral naltrexone (50 mg a day) for one to avoid returning to any drinking, and 11 for one to avoid returning to heavy drinking. (McPheeters et al., JAMA, 2023) [5]
Monthly naltrexone injections work as well as buprenorphine-naloxone once started. In a trial of 570 adults with opioid use disorder, fewer people managed to start naltrexone (72% vs 94%), but among those who started, relapse rates over 24 weeks were similar. (Lee et al., Lancet, 2018) [6]
Methylnaltrexone relieves opioid-induced constipation quickly. Across 8 trials with 2,034 participants, people given methylnaltrexone were 3.74 times more likely than those given a placebo to have a bowel movement within 4 hours, with abdominal pain as the most common side effect. (Zhang et al., Pain and Therapy, 2021) [7]
Key takeaways
Opioid antagonists block opioid receptors, mainly the mu receptor, so opioids cannot act on them.
The four main medicines are naloxone, nalmefene, naltrexone and methylnaltrexone.
Naloxone and nalmefene reverse overdoses. Naltrexone supports long-term recovery. Methylnaltrexone treats constipation caused by opioids.
The main side effect of naloxone, nalmefene and naltrexone is sudden opioid withdrawal.
If no opioids are in the body, these medicines generally have little effect.
How do opioid antagonists work?
Opioid antagonists work by binding to opioid receptors without activating them. Because they sit in the receptor, opioids cannot attach and switch it on. [1][2]
They act mainly on mu receptors. These are the receptors opioids use to relieve pain and cause their other effects. [1]
When an antagonist is given, it can stop or reverse opioid effects that are already happening. If there are no opioids in the body, it generally has little effect. [1]
What do opioids do that antagonists block?
Opioids relieve pain, but they also cause other effects. Antagonists can block all of them. [1]
Opioid effect | What it means |
Pain relief | Reduced feeling of pain |
Euphoria | A strong sense of pleasure or "high" |
Respiratory depression | Slow, shallow breathing — the main danger in an overdose |
Cough suppression | Reduced urge to cough |
Constipation | Slowed movement of the bowel |
Over time, tolerance and euphoria can lead to dependence and opioid use disorder. [1] Learn more in our guide to drug addiction (substance use disorder).
What are the main types of opioid antagonists?
The four main opioid antagonists are naloxone, nalmefene, naltrexone and methylnaltrexone. Each one has a different job. [1]
Medicine | Main use | Forms | Where it acts | Brand names |
Naloxone | Reverses opioid overdose | Nasal spray, injection | Brain and spinal cord | Narcan, Kloxxado, Zimhi, Evzio |
Nalmefene | Reverses opioid overdose | Injection | Brain and spinal cord | Revex |
Naltrexone | Long-term treatment of opioid and alcohol use disorder | Tablets, monthly injection | Brain and spinal cord | Vivitrol, ReVia, Depade |
Methylnaltrexone | Opioid-induced constipation | Tablets, injection | Mainly the gut | Relistor |
What is naloxone used for?
Naloxone is used to reverse an opioid overdose and the slowed breathing it causes. It usually restores normal breathing within about two to five minutes. Always call 911 and stay with the person, because naloxone can wear off before the opioid does; give another dose if they don't respond within 2 to 3 minutes. [1]
It comes as a nasal spray or an injection. First responders carry it, and in most places you can buy it over the counter. [1][4]
What is nalmefene used for?
Nalmefene is used to treat an acute opioid overdose. It is given as an injection or a nasal spray. [1]
It works like naloxone but lasts longer. It is used less often, and it can cause rapid withdrawal in people who are dependent on opioids. [1]
What is naltrexone used for?
Naltrexone is used as long-term (maintenance) treatment for opioid use disorder and alcohol use disorder. It blocks the sedating and euphoric effects of these substances. [1]
It does not treat withdrawal symptoms, though it can reduce cravings, especially for alcohol. It comes as daily tablets or a monthly injection. You must be off opioids for about 7 to 10 days before starting, and after stopping it the risk of a fatal overdose is higher because tolerance is lost. [1]
Naltrexone works best as part of a full treatment plan. This includes talk therapy, detox, rehabilitation and support for cravings. [1] Read more in our alcohol use disorder guide, or learn how an addiction counselor supports recovery.
What is methylnaltrexone used for?
Methylnaltrexone is used to treat constipation caused by opioids. It acts mainly on receptors in the gut, so it does not reduce opioid pain relief. [1]
It is usually prescribed for people who take prescription opioids for severe long-term pain. It comes as an injection or tablets. [1] For other causes, see our guide to constipation.
What are the side effects of opioid antagonists?
The main side effect of naloxone, nalmefene and naltrexone is opioid withdrawal. This happens because the medicine suddenly removes the opioid's effect in someone who is dependent on opioids. [1][3]
Runny nose and watery eyes
Yawning
Fast breathing
Fever
Fast heart rate
Muscle aches
Nausea, vomiting and diarrhea
Anxiety
How severe withdrawal feels depends on the person and on the opioid they used. [1]
What are the side effects of methylnaltrexone?
Methylnaltrexone does not usually cause withdrawal, because it acts mainly in the gut. Its side effects are different. [1]
Side effects of methylnaltrexone |
Stomach pain |
Gas and bloating |
Mild nausea or diarrhea |
Headache |
Muscle spasms |
Dizziness |
How is withdrawal after an opioid antagonist managed?
Withdrawal after an opioid antagonist is managed in hospital with close monitoring, IV fluids and medicines such as methadone or buprenorphine. [1]
How effective are opioid antagonists?
Naloxone and nalmefene are highly effective at reversing an overdose. Given promptly and correctly, they can save lives. [1]
Naltrexone helps people with alcohol or opioid use disorder. It works best alongside other treatment, not on its own. [1][5][6]
Medicine | How well it works |
Naloxone | Highly effective for overdose; breathing usually returns in 2–5 minutes |
Nalmefene | Highly effective for overdose; longer-lasting than naloxone |
Naltrexone | Helps recovery from opioid and alcohol use disorder, best as part of a full plan |
Methylnaltrexone | Relieves opioid-induced constipation without reducing pain relief |
Conclusion
Opioid antagonists are medicines that block opioid receptors. Naloxone and nalmefene can reverse an overdose within minutes, naltrexone supports long-term recovery from opioid and alcohol use disorder, and methylnaltrexone eases constipation without reducing pain relief.
The main thing to expect after naloxone, nalmefene or naltrexone is withdrawal. It can feel severe, but healthcare teams know how to manage it.
Keep learning. If you or someone close to you uses opioids, knowing how these medicines work is a strong first step. Read our complete guide to drug addiction, and talk with a doctor about which treatment fits your situation.
FAQ
What is the difference between naloxone and naltrexone?
Naloxone is a fast-acting medicine used to reverse an opioid overdose, while naltrexone is a long-term treatment for opioid and alcohol use disorder. Naloxone is given in an emergency as a nasal spray or injection; naltrexone is taken as daily tablets or a monthly injection. [1]
Is naloxone the same as Narcan?
Narcan is a brand name for naloxone. It is available as a nasal spray and an injection. Other naloxone brands include Kloxxado and Zimhi. [1]
How fast does naloxone work?
Naloxone usually restores normal breathing within about two to five minutes. It works best when given promptly and correctly. [1]
Can an opioid antagonist cause withdrawal?
Naloxone, nalmefene and naltrexone can cause sudden opioid withdrawal in people who are dependent on opioids. Symptoms include a runny nose, yawning, fast heart rate, muscle aches, nausea, vomiting, diarrhea and anxiety. [1][3]
Do opioid antagonists work if no opioids are in the body?
Opioid antagonists generally have little effect if no opioids are in the body. They only block or reverse opioid effects that are present. [1]
Does naltrexone stop cravings?
Naltrexone does not treat withdrawal symptoms, though it can reduce cravings, especially for alcohol. It blocks the sedating and euphoric effects of opioids and alcohol, and it works best as part of a full treatment plan. [1]
Does methylnaltrexone stop opioids from relieving pain?
Methylnaltrexone does not reduce opioid pain relief. It acts mainly on opioid receptors in the gut, where it relieves constipation. [1]
Do you need a prescription for naloxone?
No. Naloxone nasal spray is sold over the counter in the United States, so you can buy it at pharmacies and many other stores.
Should you call 911 after giving naloxone?
Yes. Call 911 right away, because naloxone can wear off before the opioids do and breathing may slow again. Stay with the person until help arrives.
Can you start naltrexone while still using opioids?
No. You usually need to be opioid-free for about 7 to 10 days before starting naltrexone, or it can trigger sudden withdrawal. Your doctor will tell you when it is safe to start.
Related Reading
Understanding Opioid Overdose: Recognition, Emergency Response, and Prevention explains the signs of opioid overdose and how to respond.
What Is Opioid Use Disorder (OUD)? Symptoms, Causes, and Recovery covers opioid use disorder and the treatments that support recovery.
What Is Opioid Withdrawal? Symptoms, Timeline, and Treatment explains withdrawal symptoms, their timeline and how they are managed.
Constipation: Symptoms, Causes, Diagnosis and Treatment — What You Need to Know covers causes of constipation, including medicines, and how to treat it.
References
Cleveland Clinic. Opioid Antagonist. Cleveland Clinic. Last updated April 5, 2023. https://my.clevelandclinic.org/health/treatments/24878-opioid-antagonist
Theriot J, Sabir S, Azadfard M. Opioid Antagonists. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Last updated January 31, 2026. https://www.ncbi.nlm.nih.gov/books/NBK537079/
Shah M, Huecker MR. Opioid Withdrawal. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Last updated July 21, 2023. https://www.ncbi.nlm.nih.gov/books/NBK526012/
National Institute on Drug Abuse. Naloxone DrugFacts. National Institute on Drug Abuse (NIDA). Last updated January 11, 2022. https://nida.nih.gov/publications/drugfacts/naloxone
McPheeters M, O'Connor EA, Riley S, et al. Pharmacotherapy for Alcohol Use Disorder: A Systematic Review and Meta-Analysis. JAMA. 2023;330(17):1653-1665. PMID 37934220. https://doi.org/10.1001/jama.2023.19761
Lee JD, Nunes EV, Novo P, et al. Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet. 2018;391(10118):309-318. PMID 29150198. https://doi.org/10.1016/S0140-6736(17)32812-X
Zhang YY, Zhou R, Gu WJ. Efficacy and Safety of Methylnaltrexone for the Treatment of Opioid-Induced Constipation: A Meta-analysis of Randomized Controlled Trials. Pain Ther. 2021;10(1):165-179. PMID 33575953. https://doi.org/10.1007/s40122-021-00237-0
Medical disclaimer
This article is for general education only and is not a substitute for professional medical advice, diagnosis or treatment. Always talk with a qualified healthcare provider about any questions you have about a medical condition or medicine. If someone may be having an opioid overdose, call your local emergency number right away.
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