Naltrexone to Treat Pain
January 17, 2022

Using Low Doses of an Opioid Antagonist (Naltrexone) to Treat Pain

by Xrystina Bicoy

What is Naltrexone?

Naltrexone is an opioid antagonist that primarily acts at the mu opioid receptors. Its action is similar to Naloxone except that it is longer acting and taken orally. Naltrexone is FDA approved for the treatment of alcohol and opioid use disorders, in which cases, it inhibits the pleasure responses from these drugs to prevent continued abuse.

How can Naltrexone be used to help relieve chronic pain?

Though Naltrexone was originally designed as an opioid antagonist, a paradoxical response of analgesia and anti-inflammation is seen when it is used at low doses (1-5 mg daily). The exact mechanism that Naltrexone uses to produce these effects is unclear. However, it is thought that low doses of Naltrexone demonstrate the following actions in the body that lead to decreased neuro-inflammatory pain:

  • Antagonism of Toll-Like Receptor 4 resulting in inhibition of downstream production of pro-inflammatory cytokines

  • Transient opioid blockade leading to a compensatory increase in endogenous opioid production, also known as an opioid rebound effect

  • Neuroprotection via microglial inhibition to decrease neuroinflammatory pain

What types of patients may benefit from treatment of Low-Dose Naltrexone (LDN)?

There is a growing body of evidence that shows LDN provides benefit in chronic pain conditions, especially those involving inflammation. The most well studied conditions include fibromyalgia, inflammatory bowel disease, multiple sclerosis, and complex regional pain syndrome.

There are other benefits of LDN that have been shown and are currently being studied. When in combination with oral opioids, LDN has been associated with lower opioid adverse effects and a lower opioid dose to achieve pain relief via the opioid rebound effect. A systematic literature review published earlier this year has also shown that patients taking LDN for chronic pain relief had experienced additional benefits in increased sleep quality and duration, and improvements in overall emotional wellbeing, mood, anxiety, and depression.


Soin A, Soin Y, Dann T, et al. Low-dose naltrexone use for patients with chronic regional pain syndrome: A Systematic Literature Review. Pain Physician. 2021;24:E393-E406.

Kim PS, Fishman MA. Low-dose naltrexone for chronic pain: update and systemic review. Curr Pain Headache Rep. 2020;24:64.

Naltrexone. Lexi-Drugs. Lexicomp. UpToDate, Inc,; 2021. Updated Dec 16, 2021. Accessed Dec 20, 2021.