Although medication is often a part of the treatment of fibromyalgia, only three have been FDA approved for the condition; for patients, it can be a challenge to find a drug that is both effective and whose side effects don’t outweigh its benefits. One emerging treatment for fibromyalgia is low dose naltrexone (LDN), which has a growing evidence base for off-label use in the treatment of fibromyalgia.
LDN has shown promising results in managing chronic pain, including fibromyalgia, when prescribed at very low doses. We’ll explore how naltrexone works, its clinical evidence, why it may be helpful for fibromyalgia, and risks or side effects associated with its use.
How Naltrexone Works
Naltrexone is an opioid receptor antagonist, which means it works by blocking the effects of opioid receptors in the brain. At typical therapeutic doses (50 mg or higher), naltrexone is primarily used to help people with substance abuse disorder or opioid addiction; it was approved by the FDA in 1984. By blocking opioid receptors, naltrexone prevents the euphoric effects of opioid drugs or alcohol dependence, which helps reduce the desire to use these substances.
However, when taken in much lower doses (usually 1 to 5 mg per day, but sometimes as low as 0.1 mg), naltrexone exerts a different effect. In low doses, it has been found to work in a unique way as a novel anti-inflammatory; it affects in the central nervous system by acting on cells that can produce inflammation when activated, known as microglial cells.
This modulation of the immune system, along with the stimulation of endorphin release, is thought to help treat conditions like fibromyalgia, chronic pain, and autoimmune diseases.
What LDN is Used For
Low dose naltrexone (LDN) is not indicated in FDA drug labeling for most of the conditions it is used to treat, but multiple clinical studies1,2,3 have investigated its potential benefits in a range of chronic conditions. LDN is typically used as an off-label treatment for conditions associated with pain, inflammation, and immune system dysregulation. Some of the conditions that LDN has been explored for include:
- Fibromyalgia: As a treatment for chronic pain associated with fibromyalgia.
- Multiple Sclerosis (MS): LDN has been used to manage symptoms of MS, including fatigue and cognitive dysfunction.
- Crohn’s Disease and Ulcerative Colitis: LDN has shown promise in treating inflammatory bowel diseases.
- Chronic Fatigue Syndrome (CFS): LDN may help alleviate the debilitating fatigue and cognitive symptoms associated with CFS.
- Autoimmune Diseases: LDN has been used to manage autoimmune diseases like rheumatoid arthritis, lupus, and Hashimoto’s thyroiditis.
Though it is not yet FDA approved for these conditions, physicians prescribe LDN off-label for fibromyalgia and other chronic conditions due to its positive safety profile and the growing body of evidence supporting its efficacy.
Why LDN is Helpful in Fibromyalgia
Fibromyalgia is a multifaceted condition with no known cure. It is characterized by widespread musculoskeletal pain, fatigue, sleep disturbances, and cognitive dysfunction, often referred to as “fibro fog.”
Below are some of the ways LDN may help those with fibromyalgia:
1. Reduction of Central Sensitization
One of the main features of fibromyalgia is central sensitization, a process in which the central nervous system becomes hyper-reactive to pain signals, amplifying the sensation of pain and making individuals more sensitive to stimuli that would not normally be felt as painful.4
LDN may help counteract central sensitization by reducing the activity of the immune system and decreasing neuroinflammation. A study published in 2021 found that LDN helped reduce hyperalgesia (increased pain sensitivity) in individuals with fibromyalgia; participants in the study doubled their pain tolerance after using the drug, suggesting that LDN could have a protective effect on the nervous system.1
2. Modulation of Immune System Function
Fibromyalgia is not classified as a rheumatic and primarily inflammatory condition, but several studies have shown that individuals with fibromyalgia often exhibit elevated levels of pro-inflammatory cytokines, which are molecules that help regulate the immune response and inflammation in the body. LDN appears to have an immunomodulatory effect, meaning that it can help balance the immune system, reducing inflammation and preventing an overactive immune response.
This immune regulation could play a role in managing the pain and inflammation often experienced by fibromyalgia patients. A study published in Arthritis and Rheumatology in 2013 found that LDN reduced pain and improved quality of life in patients with fibromyalgia.2 The researchers hypothesized that LDN’s immunomodulatory effects contributed to these improvements by reducing inflammatory markers that were elevated in fibromyalgia patients.
3. Endorphin Release and Pain Relief
Endorphins are released in response to pain, stress, and exercise; the body’s natural painkillers and mood elevators, their primary function is to block pain signals in the brain.
LDN is believed to work by briefly blocking opioid receptors, which stimulates the body to increase production of endorphins. When opioid receptors are blocked, the body perceives a temporary “lack” of endorphins, which triggers an overproduction of these pain-relieving substances.
In people with fibromyalgia, the brain may not produce enough endorphins to adequately control pain, contributing to the chronic pain experienced in the condition.3 This increase in endorphins may help alleviate the widespread pain associated with fibromyalgia.
4. Improvement of Sleep and Fatigue
Many people with fibromyalgia experience disrupted sleep, which can worsen the pain and fatigue that are fibromyalgia hallmarks. Some studies on chronic fatigue syndrome (CFS) suggest that LDN may help improve sleep quality and reduce fatigue; a 2019 study showed that 74% of patients with CFS experienced improved alertness and cognitive performance.5 However, insomnia was also a side effect in this study, suggesting more research may be needed for the improvement of sleep symptoms, particularly in fibromyalgia rather than CFS.
Risks and Side Effects of LDN
LDN is generally considered safe, particularly when used at low doses; in a systematic review of studies on LDN in fibromyalgia in 2023, no severe adverse events were reported.6 For fibromyalgia patients, this can be a major source of relief, since people who have used FDA-approved medications for the condition may have experienced side effects.
The side effects of LDN are typically mild and transient, but some patients may experience the following,7:
- Initial Increase in Symptoms: Some patients report a temporary worsening of symptoms when they first start LDN, which is often referred to as the “LDN paradoxical effect.” This effect typically occurs within the first few days to weeks of treatment and can include an increase in pain or irritability. This phase usually resolves as the body adjusts to the medication.
- Insomnia: LDN can sometimes cause difficulty sleeping, particularly when taken in the evening. To minimize this effect, some individuals take LDN in the morning or early afternoon.
- Digestive Upset: Some patients may experience mild gastrointestinal symptoms, such as nausea, bloating, or constipation, particularly when the dosage is increased too quickly.
- Headaches: Mild headaches can occur in some individuals, especially when starting the medication or adjusting the dose.
Although these side effects are generally mild, patients should monitor for any adverse effects and report them to their healthcare provider. It is also important to note that since LDN is not FDA-approved for the treatment of fibromyalgia, it is essential to work closely with a healthcare provider to determine the appropriate dose and monitor for any potential interactions with other medications.
Prescribing LDN for Fibromyalgia
While LDN has shown promise in alleviating chronic pain and improving energy levels in fibromyalgia sufferers, it is not FDA-approved for this use. As a result, patients may face reluctance from healthcare providers unfamiliar with LDN’s benefits or unsure about its efficacy in treating fibromyalgia.
Prescriptions for LDN can also be harder for pharmacies to fill, since the low doses required are not standard for conditions like opioid use disorder. Compounding pharmacies play a vital role in this process, as they can create personalized doses of LDN tailored to individual patient needs. However, not all pharmacies offer this service, so patients need to ensure they find a reliable compounding pharmacy that works with their healthcare provider.
To discuss LDN as a treatment option, it is essential to work with a provider who understands fibromyalgia and is open to working with their patients long-term to explore the dosage that works best for their unique symptoms. A fibromyalgia specialist who is familiar with the condition, like those at Swing Care, will be better equipped to evaluate the potential benefits and risks of LDN and help patients navigate the challenges of obtaining the medication.
Summary
Low dose naltrexone (LDN) represents a promising treatment option for fibromyalgia, particularly for individuals struggling with chronic pain and fatigue. The medication’s unique ability to stimulate endorphin release and reduce neuroinflammation makes it an appealing option for managing the complex symptoms of fibromyalgia. Although more research is needed to fully understand the long-term effects and optimal dosing of LDN, early clinical studies and anecdotal reports suggest that it can significantly improve the quality of life for fibromyalgia patients.
While LDN is generally considered safe, patients should consult with a healthcare provider before starting treatment, as there are potential side effects and interactions with other medications. With continued research and patient-centered care, LDN may become an important tool in the management of fibromyalgia and other chronic pain conditions.
Sources
1 Jackson D, Singh S, Zhang-James Y, Faraone S, Johnson B. The Effects of Low Dose Naltrexone on Opioid Induced Hyperalgesia and Fibromyalgia. Front Psychiatry. 2021 Feb 16;12:593842. doi: 10.3389/fpsyt.2021.593842. PMID: 33664680; PMCID: PMC7921161.
2 Younger J, Noor N, McCue R, Mackey S. Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis Rheum. 2013 Feb;65(2):529-38. doi: 10.1002/art.37734. PMID: 23359310.
3 Younger J, Noor N, McCue R, Mackey S. Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis Rheum. 2013 Feb;65(2):529-38. doi: 10.1002/art.37734. PMID: 23359310.
4 Williams DA. Phenotypic Features of Central Sensitization. J Appl Biobehav Res. 2018 Jun;23(2):e12135. doi: 10.1111/jabr.12135. Epub 2018 Jun 27. PMID: 30479469; PMCID: PMC6251410.
5 Polo, O., Pesonen, P., & Tuominen, E. (2019). Low-dose naltrexone in the treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Fatigue: Biomedicine, Health & Behavior, 7(4), 207–217. https://doi.org/10.1080/21641846.2019.1692770
6 Yang J, Shin KM, Do A, Bierle DM, Abu Dabrh AM, Yin Z, Bauer BA, Mohabbat AB. The Safety and Efficacy of Low-Dose Naltrexone in Patients with Fibromyalgia: A Systematic Review. J Pain Res. 2023 Mar 21;16:1017-1023. doi: 10.2147/JPR.S395457. PMID: 36974308; PMCID: PMC10039621.
7 Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheumatol. 2014 Apr;33(4):451-9. doi: 10.1007/s10067-014-2517-2. Epub 2014 Feb 15. PMID: 24526250; PMCID: PMC3962576.
