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For those with fibromyalgia, it’s not uncommon to use medications off label. That essentially means the medicine is being used in a way that’s different from what’s described in the licence. One such drug is naltrexone, or to be more specific, taking it at a much lower dosage than normal. Finding effective treatment options has always been an issue for those with fibro, often filled with trial and error. There’s been a lot of talk on the block lately about LDN, so today’s article is all about what it is, what it does, and what the evidence actually says about it.
What is Naltrexone?
Naltrexone was originally used to treat people with alcohol and opioid dependence. Over the last ten years or so though, it’s been explored for its potential benefits in managing fibromyalgia symptoms. In doses significantly lower than those used for addiction treatment, low dose naltrexone (LDN) has actually shown some promise across a variety of conditions, including chronic pain and autoimmune diseases. LDN is generally given in doses ranging from 1.5mg to 4.5mg per day, compared to the standard 50mg dose for addiction.
What does it do, and what does it help?
Unsurprisingly, the exact mechanism by which LDN helps with fibro symptoms isn’t fully understood. That’s largely down to the fact that fibromyalgia itself isn’t fully understood. Researchers think LDN potentially works through a few different pathways:
- Modulating immune response: LDN may reduce inflammation by modulating the activity of microglial cells in the central nervous system. These cells play a key role in neuroinflammation, which is thought to contribute to fibromyalgia pain.
- Increasing endorphin production: LDN temporarily blocks opioid receptors, prompting the body to produce more endorphins once the blockade wears off. Endorphins are natural painkillers that can reduce pain and improve mood.
- Balancing the immune system: LDN is also believed to help balance the immune system, which may be useful in conditions like fibromyalgia where there’s immune dysregulation in the picture.
So, we have a rough idea of how it’s likely working, but what does it actually help with?
Well, when it comes to LDN and fibro, the research is lacking, as you’ll see further down. But early research and anecdotal evidence point to several potential benefits of using naltrexone at a lower dose.
Pain Reduction
One of the main reasons those with fibromyalgia turn to LDN is for pain relief. Several clinical trials suggest LDN can meaningfully reduce the widespread pain associated with fibromyalgia.
Clinical trials have shown notable reductions in pain and other fibromyalgia symptoms when using LDN [1]. One study found a significant drop in daily pain, peak pain levels, fatigue, and stress in participants taking 4.5mg of LDN daily compared to placebo.
Improved Sleep
Sleep disturbances are a common issue in fibromyalgia, and the relationship between sleep and pain has been widely studied [2]. Most of the research shows that an increase in sleep disturbance comes with a sharp increase in pain (which is why amitriptyline is so often prescribed for fibromyalgia and sleep in the first place).
It’s well established that poor sleep directly drives more pain, and also causes a swift decline in physical functioning and mood, especially during the early parts of the next day, often making other symptoms like pain and fatigue worse [3]. Anecdotal reports and smaller studies suggest that those on LDN tend to experience better sleep quality [4]. Better sleep then loops back into reduced pain and better daytime functioning. By helping people achieve more restful sleep, LDN indirectly helps manage fibromyalgia symptoms more effectively.
Improved Quality of Life
Beyond reducing pain and improving sleep, LDN has been reported to improve the overall quality of life for those with fibromyalgia. That includes improvements in mood, energy, and day to day functioning.
In one study evaluating the effects of LDN, participants noted significant improvements in mood and life satisfaction [4]. Another observed a significant decrease in inflammatory cytokine levels, which correlated with subjective improvements in pain, mood, and satisfaction. That suggests LDN’s anti inflammatory effects may be part of the picture when it comes to quality of life.
What does the research say about a low dose?
So, it’s looking decent from a proposed benefits point of view. When it comes to side effects and dangers, LDN is pretty safe, much more so than a lot of other drugs given to those with fibro. While traditional medications like opioids or certain antidepressants come with a slew of side effects (drowsiness, dependency, gut issues), LDN used in low doses tends to present only mild side effects like occasional nausea or vivid dreams. It also doesn’t carry the risk of addiction, which makes it a more appealing option for long term management. Its impact on liver health is negligible compared to other high dose treatments, making it a safer choice for continuous use than some other fibro drugs.
The research into low dose naltrexone as a treatment is still in its early stages. The initial findings are promising, but the research is fraught with challenges. The main issue is the lack of large scale, rigorous clinical trials. Most studies so far have been small pilot trials or case studies, which are informative, but don’t give the robust data needed for broad clinical recommendations.
A systematic review out of the Mayo Clinic highlighted the general safety and efficacy of LDN for fibromyalgia. It noted that side effects are typically mild (insomnia, vivid dreams), but larger, more comprehensive studies are needed to fully understand the benefits and risks. One thing to flag, that review excluded people with chronic fatigue syndrome (CFS), a condition that often co occurs with fibromyalgia, which limits how well the findings apply to the broader fibromyalgia population.
One significant pilot study, published in Pain Medicine, found that LDN reduced fibromyalgia symptoms by over 30% compared to placebo, suggesting a real effect on pain and other symptoms like fatigue and stress. Despite these encouraging results, the study’s single blind, crossover design and small sample size limit how generalisable the findings are [4]. A larger fourteen year retrospective analysis since then has also pointed to LDN as a viable option for chronic pain conditions like fibromyalgia [5]. The authors of the earlier pilot called for larger, double blind, placebo controlled trials to confirm those initial findings and to better understand the underlying mechanisms of LDN’s effects on fibromyalgia symptoms.
Another notable trial conducted in Denmark is currently underway, aiming to evaluate LDN in a more structured and larger sample [6, 7]. This double blind, randomised, placebo controlled trial includes 100 women with fibromyalgia, assessing a range of outcomes from pain intensity to quality of life over a 12 week period. The structured approach of this study promises to add much needed depth to our understanding of LDN’s potential as a treatment option.
In summary, early studies suggest that LDN could be a safe and effective treatment for fibromyalgia, but the current research is limited by small sample sizes, exclusion criteria, and methodological constraints. Larger, well designed trials are essential to validate these findings and to establish LDN as a reliable treatment option for those with fibromyalgia.
— The Fibro Guy Team —
FAQ on Low Dose Naltrexone
What should you avoid when taking LDN?
When taking LDN it’s important to avoid opioid medications and alcohol. Opioids can block the effectiveness of LDN, and using them together can cause withdrawal symptoms. Always check with your healthcare provider about any other medications or supplements you’re on, to avoid potential interactions.
Is long term use of LDN safe?
Long term use of LDN is generally considered safe, with minimal side effects. Unlike higher doses used for addiction treatment, LDN doesn’t pose significant risks of liver damage or dependency. Some people may experience persistent mild side effects like vivid dreams or insomnia, but these are generally manageable. Always discuss long term use with your healthcare provider to make sure it’s safe for your specific health situation.
What are the common side effects of LDN?
Common side effects of LDN include mild symptoms such as insomnia, vivid dreams, headaches, and nausea. These side effects are generally mild and often settle down over time.
How does LDN reduce inflammation?
It reduces inflammation by modulating microglial cell activity in the central nervous system.
How does LDN help fibromyalgia symptoms?
LDN helps fibromyalgia symptoms by reducing inflammation and modulating the immune response, particularly through its effects on microglial cells in the central nervous system. It also boosts the body’s natural painkillers, like endorphins, which can improve mood and reduce pain. On top of that, LDN has been reported to improve sleep quality, reduce fatigue, and improve overall quality of life for many people taking it.
References:
- Australian Journal of General Practice. (2023). Low dose naltrexone in the treatment of fibromyalgia. [online] Available at: https://www1.racgp.org.au/ajgp/2023/april/low-dose-naltrexone-in-the-treatment-of-fibromyalg.
- Andersen, M.L., Araujo, P., Frange, C. and Tufik, S. (2018). Sleep disturbance and pain. Chest, 154(5), pp.1249 to 1259. doi: 10.1016/j.chest.2018.07.019.
- Gerhart, J.I., Burns, J.W., Post, K.M., Smith, D.A., Porter, L.S., Burgess, H.J., Schuster, E., Buvanendran, A., Fras, A.M. and Keefe, F.J. (2017). Relationships between sleep quality and pain related factors for people with chronic low back pain: tests of reciprocal and time of day effects. Annals of Behavioral Medicine, 51(3), pp.365 to 375. doi: 10.1007/s12160-016-9860-2.
- Younger, J. and Mackey, S. (2009). Fibromyalgia symptoms are reduced by low dose naltrexone: a pilot study. Pain Medicine, 10(4), pp.663 to 672. doi: 10.1111/j.1526-4637.2009.00613.x.
- Driver, C.N. and D’Souza, R.S. (2023). Efficacy of low dose naltrexone and predictors of treatment success or discontinuation in fibromyalgia and other chronic pain conditions: a fourteen year, enterprise wide retrospective analysis. Biomedicines, 11(4), p.1087. doi: 10.3390/biomedicines11041087.
- ClinicalTrials.gov. (2025). NCT04270877. [online] Available at: https://clinicaltrials.gov/study/NCT04270877.
- Bruun, K.D., Amris, K., Vaegter, H.B., Blichfeldt-Eckhardt, M.R., Holsgaard-Larsen, A., Christensen, R. and Toft, P. (2021). Low dose naltrexone for the treatment of fibromyalgia: protocol for a double blind, randomised, placebo controlled trial. Trials, 22(1). doi: 10.1186/s13063-021-05776-7.
The Full Body Fibro Tool Box
The tool box brings together education on pain and movement alongside a wide range of practical movement, stretching and sensory based resources. Rather than offering a single plan or set of rules, it gives you options you can return to and use as needed.
