Ask CLYR: Early small studies of LDN in fibromyalgia were encouraging, but the two largest placebo-controlled trials, published in 2024 and 2026, did not find a meaningful benefit over placebo for pain. LDN is still prescribed off-label in some cases, and a provider weighs that mixed evidence with you.
Fibromyalgia is the condition where low-dose naltrexone (LDN) has been studied most. LDN is a compounded capsule, not FDA-approved at this dose, and any use for fibromyalgia is off-label. The story of the research is a familiar one in medicine: small early studies looked encouraging, and larger, longer trials did not confirm them. This article lays out that evidence in order. For the basics, see what low-dose naltrexone is.
The short answer
The evidence is mixed. Small early studies reported lower pain scores. The two largest and longest placebo-controlled trials, a 2024 trial of 6 mg and a 12-month 2026 trial of 4.5 mg, did not find a meaningful benefit over placebo.
Timeline of studies
| Study | Design | Dose | What it found |
|---|---|---|---|
| Younger and Mackey, 2009 | Single-blind pilot, small | 4.5 mg | Symptoms down more than 30% vs placebo period |
| Younger et al., 2013 | Crossover randomized trial, 31 people | 4.5 mg | Daily pain down 28.8% vs 18.0% on placebo |
| Bruun-Plesner et al., 2020 | Dose-finding, 25 evaluable | 0.75 to 6 mg | Estimated response at 3.88 mg (half of people) and 5.40 mg (95%); not an efficacy test |
| Due Bruun et al., 2024 | Parallel randomized trial, 99 women, 12 weeks | 6 mg | Not better than placebo for pain (difference 0.34 points, p=0.27) |
| Rodríguez-Freire et al., 2026 | Randomized trial, 12 months | 4.5 mg | No clinically meaningful benefit over placebo (p=0.236) |
The negative trials are the largest and the longest. The 2026 trial is the most recent and ran for a full year.
What the meta-analyses say, and why they disagree
Three recent pooled analyses reached different conclusions, partly because they included different studies.
- Vatvani et al., 2024: four randomized trials, 222 people. Pain was lower with LDN than placebo on average. More vivid dreams and nausea were reported with LDN.
- Hegde et al., 2025: chronic pain trials. For fibromyalgia, a small effect compared with placebo (effect size 0.34). Adverse events were more frequent with LDN (incidence rate ratio 1.4).
- Ologunowa et al., 2025: eight studies. People improved from where they started, but LDN was not superior to placebo.
None of these analyses includes the 12-month trial published in 2026, which was negative. Side effects across these studies are covered in LDN side effects: what the studies reported.
Why early results may not hold
Early studies were small, short and often used crossover designs, where each person takes both LDN and placebo in turn. Those designs are useful for a first look but can overstate an effect. Fibromyalgia symptoms also go up and down on their own, and placebo responses in pain trials are large. Larger parallel trials with separate placebo groups give more reliable answers. The same pattern, early uncontrolled reports followed by a need for controlled trials, shows up in the long COVID research.
Is it still prescribed?
Yes. LDN may be prescribed off-label when a licensed provider judges it appropriate, after a clear conversation about this mixed evidence. That is a clinical judgment for one person, not a promise that it will help. Most fibromyalgia trials used 4.5 mg; how that dose was chosen is explained in LDN dosing: why 4.5 mg.
Talking to a provider, and cost
If you want to discuss LDN, be ready to share your full medicine list and health history, including any liver problems. At CLYR, a licensed provider reviews your screening and decides whether LDN is appropriate for you. At CLYR, low-dose naltrexone 4.5 mg is $119 for 30 capsules or $169 for 90 capsules. Each order is billed once and nothing renews. Provider review and shipping are included, and your provider sets the days of supply. See the LDN page for details.
Frequently asked questions
Does LDN work for fibromyalgia?
The evidence is mixed. Small early trials reported less pain, but larger trials in 2024 and 2026 did not show a meaningful benefit over placebo.
What dose was used in fibromyalgia trials?
Most used 4.5 mg; one large trial used 6 mg. A dose-finding study estimated 3.88 mg as the dose where half of people responded.
Why do some studies disagree?
Early studies were small and short. Larger, longer trials with placebo groups give more reliable answers, and they were negative.
Can a provider still prescribe it?
Yes. LDN may be prescribed off-label when a provider judges it appropriate, with a clear conversation about the evidence.
Important safety information
Compounded low-dose naltrexone is a prescription capsule dispensed only after a licensed provider independently reviews your intake and determines it is appropriate for you. Do not take naltrexone if you take any opioid medicine or have taken one in the last 14 days, including tramadol, codeine, methadone or buprenorphine, because naltrexone blocks them and can cause sudden withdrawal; do not take it if you currently take or need opioid medicines, have liver disease, hepatitis or abnormal liver tests, or are allergic to naltrexone. Tell your provider about kidney disease, pregnancy, breastfeeding or plans for pregnancy, and about every medication and supplement you take. Side effects may include vivid dreams, trouble sleeping, headache, nausea, dizziness or anxiety. Carry a note that you take naltrexone, because opioid pain medicines may not work normally while it is in your system. Compounded medications are made by a licensed U.S. 503A pharmacy to a provider's prescription; they are not FDA-approved and have not been reviewed by the FDA for safety or effectiveness. Individual results vary. Not everyone qualifies. This page is informational and is not medical advice. Call 911 in an emergency.
The same text appears in the Important Safety Information on the LDN page.