Does low-dose naltrexone actually reduce fibromyalgia pain?
The short answer is: it might, but the strongest evidence says it does not work better than a placebo. A 2025 meta-analysis that combined results from five randomized controlled trials (the gold standard of medical research) found that LDN was superior to placebo for reducing pain, with a moderate effect size (standardized mean difference -0.61) [1]. Another 2013 crossover trial in 31 women reported a 28.8% reduction in daily pain with LDN compared to 18.0% with placebo [6]. These numbers sound promising, but they come from smaller, older studies.
The picture changes when you look at the largest, most rigorous trial to date. In 2023, a placebo-controlled trial of 99 women with fibromyalgia found that after 12 weeks, pain dropped by 1.3 points on an 11-point scale with LDN and by 0.9 points with placebo—a difference that was not statistically significant (p=0.27) [2]. This means the improvement could easily be due to chance or the placebo effect. The same trial also noted that LDN might improve memory problems, but that was a secondary finding [2]. So while some patients may benefit, the best current evidence suggests LDN is not reliably better than a sugar pill for pain.
Who is most likely to get relief from LDN?
Not everyone with fibromyalgia responds the same way to LDN, and the evidence points to a few patterns. A 2024 retrospective review of 136 patients at a VA hospital found that, on average, pain scores dropped from 7.1 to 6.4 on a 10-point scale after starting LDN—a small but statistically significant reduction [5]. However, only about 17% of patients experienced a 30% or greater reduction in pain, meaning the majority saw little benefit [5]. Another 2024 study of 31 chronic pain patients found that while average pain scores improved slightly, 87% of patients stopped taking LDN, mostly because it didn't help enough [3].
The type of pain may matter. A 2023 case series of 70 patients who actually took LDN found that 64% reported some relief, but those with neuropathic pain (nerve-related pain) or complex regional pain syndrome were significantly more likely to respond than those with spondylosis (a type of arthritis) [7]. For fibromyalgia specifically, a 2021 open-label study of 21 patients found that LDN doubled pain tolerance on a cold pressor test (a measure of how long you can keep your hand in ice water), suggesting it may help with central pain sensitivity [4]. The bottom line: LDN seems to work best for people with nerve-related pain, and even then, many don't get enough relief to keep taking it.
Is LDN safe, and what are the side effects?
LDN is generally safe and well-tolerated, but it does have side effects. The 2025 meta-analysis found no increase in headaches with LDN compared to placebo, but it did find a significantly higher rate of vivid dreams—about 2.4 times more common with LDN [1]. In the 2023 large trial, 84% of patients on LDN reported some adverse event (versus 86% on placebo), and 8% stopped the drug due to side effects, compared to 6% in the placebo group [2]. No serious adverse events were linked to LDN in any of the studies reviewed [1][2][6].
The most common reasons people stop LDN are lack of benefit (52% in one study) and loss of benefit over time (23%) [3]. Only about 10% stopped due to side effects [3]. A 2023 review noted that LDN is as effective as amitriptyline for painful diabetic neuropathy but has a better safety profile [8]. For fibromyalgia, doses as low as 4.5 mg per day are typical, and the medication is inexpensive and widely available [6]. The takeaway: LDN is low-risk, but it's not a magic bullet—most people who try it stop because it doesn't help enough.
About These Sources
This answer is built on 8 peer-reviewed studies — published from 2013 to 2025, 3 from 2024 or later, 3 in Q1–Q2 journals, collectively cited 77 times — selected as the most relevant from 13 studies that passed quality screening, drawn from 46 papers retrieved from a database of over 500 million.
Sources used in this answer
Efficacy and safety of low-dose naltrexone (LDN) in fibromyalgia: a systematic review and meta-analysis
This 2025 meta-analysis of five RCTs found LDN superior to placebo for pain reduction (SMD -0.61) but not for mechanical pain threshold; vivid dreams were more common with LDN (RR 2.41).
Naltrexone 6 mg once daily versus placebo in women with fibromyalgia: a randomised, double-blind, placebo-controlled trial.
This 2023 placebo-controlled trial in 99 women found no significant difference between LDN and placebo for pain reduction (between-group difference -0.34, p=0.27); LDN may improve memory problems.
Efficacy and Safety of Low Dose Naltrexone for Chronic Pain
This 2024 retrospective cohort study of 31 patients found a statistically significant but small reduction in pain scores with LDN; 87% discontinued, mostly due to lack of benefit.
The Effects of Low Dose Naltrexone on Opioid Induced Hyperalgesia and Fibromyalgia
This 2021 open-label case series of 21 fibromyalgia patients found LDN doubled pain tolerance on the cold pressor test, with a large effect size (r=0.63).
A Utilization Review of Patients That Respond to Low-Dose Naltrexone (LDN) for Chronic Pain at a Single Institution
This 2024 retrospective review of 136 patients (including those with fibromyalgia) found a small but significant reduction in pain scores (from 7.1 to 6.4) with LDN; 17% had ≥30% pain reduction.
Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels.
This 2013 crossover RCT in 31 women found LDN reduced daily pain by 28.8% versus 18.0% with placebo (p=0.016) and improved mood and life satisfaction.
Low-Dose Naltrexone (LDN) for Chronic Pain at a Single Institution: A Case Series
This 2023 case series of 70 patients who took LDN found 64% reported relief; those with neuropathic pain or CRPS were more likely to respond than those with spondylosis.
Is low-dose naltrexone effective in chronic pain management?
This 2023 review states LDN is as effective as amitriptyline for painful diabetic neuropathy with a superior safety profile, and doses as low as 5.4 mg reduced pain in 95% of fibromyalgia patients in one study.