Low-dose naltrexone (LDN) is an off-label treatment some doctors prescribe for fibromyalgia. Small early studies looked hopeful, but two larger placebo-controlled trials, published in 2023 and 2026, found it did not lower pain more than a placebo. The research on low dose naltrexone for fibromyalgia is still mixed, so it is best seen as an unproven option to discuss with your doctor, not a sure thing.
You may have seen LDN talked about in online groups as a breakthrough. Let’s look at what the studies actually found, so you can have an informed talk with your care team.
What Is Low-Dose Naltrexone?
Naltrexone is an FDA-approved medicine used to help people recover from alcohol or opioid use disorder. At its usual dose, it blocks the effects of opioids in the body.
“Low-dose” naltrexone uses a much smaller amount, usually just a few milligrams a day. In fibromyalgia studies, doses have ranged from about 4.5 mg to 6 mg once a day. Because these small doses are not sold as standard tablets, LDN is often made by a compounding pharmacy.
LDN Is Off-Label for Fibromyalgia
The FDA has not approved naltrexone for fibromyalgia. When a doctor prescribes a medicine for something other than its approved use, it is called “off-label” use. This is legal and common, but it means the drug has not gone through the full review for that purpose.
Off-label use also has practical effects:
- Insurance may not cover it.
- Doses and quality can vary between compounding pharmacies.
- There is less research on long-term safety for this use.
How LDN Might Work (The Theory)
No one knows for sure how LDN might help fibromyalgia. The main theories are:
- Calming immune cells in the nervous system. Some researchers think low doses may quiet glial cells, which are support cells in the brain and spinal cord that can release substances linked to pain and inflammation.
- A rebound in the body’s own painkillers. Briefly blocking opioid receptors might lead the body to make more of its natural pain-relieving chemicals, called endorphins.
These ideas are interesting, but they are still theories. A 2026 review in Clinical and Experimental Rheumatology described LDN as still showing potential for calming nervous system inflammation and pain sensitivity. But potential is not proof, and research is ongoing.
The Early Studies
The first LDN studies in fibromyalgia came from Stanford University.
- 2009 pilot study: Ten women with fibromyalgia took part. The researchers reported pain and fatigue dropped by an average of about 30 percent compared with placebo. They called the results preliminary.
- 2013 crossover study: Thirty-one women took 4.5 mg of naltrexone daily and also took a placebo at a different time. Pain dropped 28.8 percent on LDN versus 18 percent on placebo. About a third of women met the study’s definition of a response on LDN, compared with 11 percent on placebo. LDN was rated about as tolerable as placebo.
These results caught a lot of attention. But both studies were very small, and small studies can give results that do not hold up in larger trials.
The 2023 Danish Randomized Trial
To test LDN more carefully, researchers in Denmark ran a larger trial called FINAL. Results were published in The Lancet Rheumatology in December 2023.
Here is what they did and found:
- Who: 99 women with fibromyalgia
- What: Naltrexone 6 mg once a day or a placebo, for 12 weeks
- Design: Randomized and double-blind, meaning neither patients nor researchers knew who got which pill
- Main result: Both groups had some drop in pain. But the LDN group did not improve significantly more than the placebo group.
- Side effects: Side effects were reported at similar rates in both groups.
The authors noted LDN might help memory problems related to fibromyalgia and said more study is needed. A follow-up paper in 2025, in the journal CNS Drugs, looked at other measures, like pain tolerance and muscle endurance. It also did not find clear benefits, and one positive finding was judged likely to be due to chance.
This trial included only women, so the results may not apply equally to men.
A 12-Month Trial From Spain (2026)
A second, longer trial was published in the European Journal of Pain in 2026. Researchers in Spain gave 98 women with fibromyalgia either LDN 4.5 mg or a placebo every evening for 12 months.
- Main result: At 3 months, pain did not improve more with LDN than with placebo. There was also no clear difference at 6 or 12 months.
- Other measures: Changes in daily function, mood, thinking and disability were small and similar in both groups.
- Side effects: LDN was generally well tolerated, though nervous system side effects were reported more often in the LDN group.
The authors concluded that their results do not support routine use of LDN 4.5 mg for fibromyalgia. Like the Danish trial, it included only women.
What Newer Reviews Say (2025 to 2026)
Researchers have also tried to pool the results of all the LDN studies together. The findings point in different directions:
- 2025 meta-analysis: A review of five randomized trials in Annals of Medicine and Surgery concluded LDN reduced pain compared with placebo and had no serious side effects. It also found vivid dreams were more than twice as common with LDN.
- 2026 re-analysis: A letter in The Korean Journal of Pain re-checked the data from an earlier review and corrected some errors. It found more people on LDN had at least a 30 percent drop in pain, but the overall difference in pain scores was not statistically significant. The authors said the benefit was smaller than the earlier review had reported.
In plain terms: the evidence is mixed. Some people in studies did better on LDN, but the two largest placebo-controlled trials did not find a clear benefit over placebo. Larger, longer trials that include men are still needed.
Possible Side Effects
In studies, LDN has generally been well tolerated. Side effects that have been reported include:
- Vivid or unusual dreams
- Trouble sleeping
- Headache
- Nausea or upset stomach
MedlinePlus also lists signs of possible liver problems as serious side effects of naltrexone. These include yellow skin or eyes, dark urine, light-colored stools, and pain in the upper right belly. Call your doctor right away if you notice any of these.
Who Should Not Take LDN
LDN is not safe for people who take opioid pain medicine. This includes tramadol, oxycodone, hydrocodone, codeine, and others. Naltrexone blocks opioids. Taking it with opioids can:
- Cause sudden opioid withdrawal
- Make your opioid pain medicine stop working
- Lead to dangerous overdose if someone takes more opioids to try to overcome the block
MedlinePlus notes that naltrexone is not given to people who have recently used opioids or are in withdrawal, and that after stopping naltrexone, a person may be more sensitive to opioids.
You should also talk carefully with your doctor about LDN if you:
- Have liver or kidney disease
- Are pregnant, planning pregnancy, or breastfeeding
- Might need surgery or emergency care where opioid pain medicine could be used
Always tell every doctor, dentist, and emergency team that you take naltrexone, even at a low dose.
How to Talk to Your Doctor About LDN
If you are curious about LDN, bring it up with your doctor. It helps to go in prepared. You might ask:
- “Do you think LDN is a reasonable option for me, given what the research shows?”
- “Are any of my current medicines a problem with naltrexone?”
- “What dose would we start with, and how long would we try it?”
- “How will we know if it is working?”
- “Which pharmacy would make it, and what will it cost?”
Bring a full list of your medicines and supplements. Be ready to hear “no” if LDN does not fit your health history. Never start LDN on your own or buy it from an unreliable online source, and never change or stop your other medicines without your doctor’s guidance.
It also helps to keep the bigger picture in mind. Exercise, sleep care, and FDA-approved medicines have stronger evidence for fibromyalgia. LDN, if you try it, is usually one piece of a larger plan.
Frequently Asked Questions
Is low dose naltrexone FDA-approved for fibromyalgia?
No. Naltrexone is FDA-approved for alcohol and opioid use disorder. Using it at low doses for fibromyalgia is off-label, which means your doctor would prescribe it outside its approved use.
Does LDN work for fibromyalgia?
The research is mixed. Small early studies were hopeful, but randomized trials published in 2023 and 2026, each with about 100 women, found LDN did not reduce pain more than placebo. Newer reviews disagree on how much benefit, if any, it offers.
Can I take LDN with tramadol or other opioids?
No. Naltrexone blocks opioids and can cause sudden withdrawal or make your pain medicine stop working. Tell your doctor about every medicine you take before starting LDN.
What are the most common side effects of LDN?
Vivid dreams are the side effect reported most often in studies. Some people also have trouble sleeping, headaches, or nausea. Side effects are usually mild, but tell your doctor about anything that bothers you.
The Bottom Line
Low-dose naltrexone is an off-label option for fibromyalgia with mixed research behind it. Small early studies looked promising, but the two largest trials to date did not show a clear benefit over placebo. It is not safe for anyone taking opioid pain medicine. If you are interested, have an honest talk with your doctor about whether the possible benefits outweigh the costs and risks for you.
Sources
- Naltrexone 6 mg once daily versus placebo in women with fibromyalgia: a randomised, double-blind, placebo-controlled trial (The Lancet Rheumatology, 2023)
- Efficacy of Low-Dose Naltrexone in Women With Fibromyalgia Syndrome: A 12-Month Randomised, Double-Blind, Placebo-Controlled Trial (European Journal of Pain, 2026)
- Efficacy and safety of low-dose naltrexone (LDN) in fibromyalgia: a systematic review and meta-analysis (Annals of Medicine and Surgery, 2025)
- Low-dose naltrexone for fibromyalgia: a re-analysis suggests lower efficacy than previously reported (Korean Journal of Pain, 2026)
- Low-dose naltrexone shows no significant effects in fibromyalgia (Rheumatology Live, 2025)
- Naltrexone (MedlinePlus)
New from Anna Curran, RN
Fibromyalgia: A Nurse’s Guide to Less Pain, Better Sleep and More Good Days
A plain-language guide to medicines, pacing, sleep, gentle movement, flares, work and family life, with trackers and planners. Paperback, hardcover and Kindle.
This article is for general education only and is not medical advice. Talk with your own doctor or licensed provider before you start, stop or change any treatment. In an emergency, call 911. In crisis, call or text 988. See our medical disclaimer.