Naltrexone is a drug typically given to people with opioid addiction. Opioids like morphine or heroin work by activating the mu receptor.  Naltrexone blocks this receptor, thus blocking the effects of heroin, morphine etc.  Low-dose naltrexone has been demonstrated to reduce symptom severity in conditions such as fibromyalgia, Crohn’s disease, multiple sclerosis, and complex regional pain syndrome.  The effects are, in theory, are not due to working on the opioid receptor but on the microglia.   Microglia are a type of glial cell located throughout the brain and spinal cord. Microglia account for 10–15% of all cells found within the brain. As the resident macrophage cells (macrophages are cells that eat things that aren’t supposed to be there) , they act as the first and main form of active immune defense in the central nervous system. Microglia are distributed in large non-overlapping regions throughout the CNS. Microglia are key cells in overall brain maintenance.

Naltrexone is FDA approved for opioid addiction and prescribed in doses of 50 to 100 mg/day. Low dose naltrexone are provided in less than 1/10 of that dose, i.e. less than 4/5 mg/day. Low doses, strangely enough seem to provide pain relief and is anti-inflammatory.

Fibromyalgia is characterized by diffuse musculoskeletal pain, fatigue, concentration problems and difficulty sleeping. Fibromyalgia does not respond will to typical anti-inflammatory medications.  There are two small clinical trials showing 4.5 mg/day at bedtime reduced the fibromyalgia pain greater than placebo.

Mechanistically, naltrexone works on a receptor, the Toll-like receptor 4 or TLR4 receptor on microglia. This is how it has an anti-inflammatory effect.  Microglia protect the central nervous system by causing inflammation.  However, this chronic inflammation causes sensitivity, fatigue, sleep disruption etc.  Naltrexone has been demonstrated to exert neuroprotective effects and pain relieving effects.  Naltrexone is also thought to have an anti-inflammatory effect in the body by reducing inflammation caused by macrophages (a type of white blood cell that kills bacteria etc).  The science behind how naltrexone works is in the early stages and more research is needed.   Interestingly, a lab test, the erythrocyte sedimentation rate (ESR) was predictive of success with low dose naltrexone.  Individuals with a higher ESR rate were more likely to benefit from low dose naltrexone.

Low dose naltrexone also has efficacy in other known inflammatory disorders such as Crohn’s disease with a response rate of up to 80% in some studies, multiple sclerosis however benefit is weak for multiple sclerosis, and it may be helpful in complex regional pain syndrome. It is important to note that low dose naltrexone and standard dose naltrexone have very different effects.  Caution is also noted in that naltrexone has a long history of safe use in larger doses, very little is known about long term low dose use.  Theoretically, inhibition of the immune system could raise risk of infection or cancer, however to date no such reports exist.

It is noted that low dose naltrexone is not FDA approved and is still under investigation. However, there are advantages: low cost, approximately $35 a month and low risk of side effects or withdrawal symptoms.  Most common  side effects are mild and can include vivid dreams or nightmares which typically get better with time.  People also report headaches but this must be distinguished in fibromyalgia patients as they frequency have headaches.

In summary, low dose naltrexone must be prescribed and should only be taking in consultation with your health care provider. The is promise that low dose naltrexone can help not only fibromyalgia but also other inflammatory conditions.

The Research

Clin Rheumatol. 2014 Apr;33(4):451-9. doi: 10.1007/s10067-014-2517-2. Epub 2014 Feb 15.

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

Younger J¹, Parkitny L, McLain D.

Author information

• ¹Stanford University, Stanford, CA, USA, jyounger@stanford.edu.

Abstract

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.