Review Article

Clinical Rheumatology

, Volume 33, Issue 4, pp 451-459

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain

  • Jarred YoungerAffiliated withStanford UniversityDepartment of Anesthesia, Pain and Perioperative Medicine, Stanford University Email author 
  • , Luke ParkitnyAffiliated withDepartment of Anesthesia, Pain and Perioperative Medicine, Stanford University
  • , David McLainAffiliated withMcLain Medical Associates


Low-dose naltrexone (LDN) has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn’s disease, multiple sclerosis, and complex regional pain syndrome. We review the evidence that LDN may operate as a novel anti-inflammatory agent in the central nervous system, via action on microglial cells. These effects may be unique to low dosages of naltrexone and appear to be entirely independent from naltrexone’s better-known activity on opioid receptors. As a daily oral therapy, LDN is inexpensive and well-tolerated. Despite initial promise of efficacy, the use of LDN for chronic disorders is still highly experimental. Published trials have low sample sizes, and few replications have been performed. We cover the typical usage of LDN in clinical trials, caveats to using the medication, and recommendations for future research and clinical work. LDN may represent one of the first glial cell modulators to be used for the management of chronic pain disorders.


Anti-inflammatory Chronic pain Fibromyalgia Glial cell modulators Low-dose naltrexone Microglia