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LDN3.8

Low-Dose Naltrexone (LDN) Research

Mostly mechanism / observationalLimited safety

7 peer-reviewed studies

What the evidence says

Mostly mechanism / observational

Most Low-Dose Naltrexone (LDN) studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.

Most evidence is from mixed-quality meta-analyses and randomised trials published 2007–2025 with a typical study size of 31 participants.

Based on 7 studies · 1 meta-analysis · 3 RCTs · 234 total participants

Confidence

Moderate

By outcome

Pain & fibromyalgia
Mostly mechanism / observational4 studies
Inflammation & autoimmune
Mostly mechanism / observational3 studies
Autoimmune & neurological conditions
Mostly mechanism / observational3 studies
Safety profile
Too few graded studies1 study

Steady research

2 studies in the last 5 years · Latest meta-analysis: 2025

200720162025

1Systematic Review2025

LDN reduced pain and symptom severity from baseline, but these effects were not superior to placebo.

Ologunowa, Otoo, Caffrey, Buchanan, Eze, Vyas · Journal of pain & palliative care pharmacotherapy (2025)

Systematic review and meta-analysis of 8 fibromyalgia studies
LDN lowered pain and symptom severity versus baseline, but pooled change was NOT statistically superior to placebo
Best contradicting evidence — tempers the single-trial pain signal

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2Meta-Analysis2025

LDN was better than placebo in fibromyalgia pain, but showed no overall difference across chronic-pain syndromes.

Hegde, Mishra, V, Maiti, Hota, Srinivasan · Current pain and headache reports (2025)

Meta-analysis of 7 randomized trials of LDN across chronic-pain conditions
No significant overall pain benefit vs control, but a significant subgroup benefit in fibromyalgia (d = -0.34, P = 0.019)
Adverse events were modestly higher on LDN than placebo (IRR 1.4)

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3RCTn=31 · small study2013

Low-dose naltrexone produced a significantly greater reduction in fibromyalgia pain than placebo (28.8% vs 18.0%).

Younger, Noor, McCue, Mackey · Arthritis and rheumatism (2013)

Randomized, double-blind, placebo-controlled crossover trial of 4.5 mg/day naltrexone in 31 women with fibromyalgia
Significantly greater baseline pain reduction on LDN than placebo (28.8% vs 18.0%, P = 0.016); improved mood and life satisfaction
The strongest randomized human evidence for an LDN pain effect

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4RCTn=96 · small study2010

Quality-of-life measures did not differ meaningfully between low-dose naltrexone and placebo in MS.

Sharafaddinzadeh, Moghtaderi, Kashipazha, Majdinasab, Shalbafan · Multiple sclerosis (Houndmills, Basingstoke, England) (2010)

Randomized, double-blind, placebo-controlled trial of LDN in 96 MS patients using the MSQoL-54
Most quality-of-life domains showed NO statistically significant difference vs placebo
Best counter-evidence for the autoimmune QoL claim — a larger MS trial that was null

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5RCTn=80 · small study2010

Low-dose naltrexone significantly improved mental-health quality-of-life indices in multiple sclerosis.

Cree, Kornyeyeva, Goodin · Annals of neurology (2010)

Double-masked, placebo-controlled crossover pilot of 4.5 mg nightly naltrexone in MS (80 enrolled, 60 completed)
Significant improvement on mental-health QoL measures (SF-36 mental component, Mental Health Inventory, Pain Effects Scale)
Outcome anchor for the MS/autoimmune use

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6Pilotn=10 · very small study2009

Low-dose naltrexone reduced fibromyalgia symptoms by more than 30% over placebo.

Younger, Mackey · Pain medicine (Malden, Mass.) (2009)

Single-blind crossover pilot of 4.5 mg naltrexone in 10 women with fibromyalgia
>30% symptom reduction over placebo; improved mechanical and heat pain thresholds
Foundational human study; higher baseline ESR predicted greater response (an inflammatory rationale)

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7Observationaln=17 · very small study2007

Low-dose naltrexone therapy appeared effective and safe in subjects with active Crohn's disease.

Smith, Stock, Bingaman, Mauger, Rogosnitzky, Zagon · The American journal of gastroenterology (2007)

Open-label pilot prospective trial of 4.5 mg/day naltrexone in 17 patients with active Crohn's disease
Crohn's Disease Activity Index fell significantly; 89% responded and 67% reached remission
Foundational autoimmune/inflammatory-bowel signal for LDN

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View in Research Library

Low-Dose Naltrexone (LDN) Research

Mostly mechanism / observational

Efficacy of Low-Dose Naltrexone in Treating Patients with Fibromyalgia: systematic Review and Meta-Analysis.

Low Dose Naltrexone In The Management Of Chronic Pain Syndrome: A Meta-Analysis Of Randomized Controlled Clinical Trials.

Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels.

The effect of low-dose naltrexone on quality of life of patients with multiple sclerosis: a randomized placebo-controlled trial.

Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis.

Fibromyalgia symptoms are reduced by low-dose naltrexone: a pilot study.

Low-dose naltrexone therapy improves active Crohn's disease.