Low-dose naltrexone (LDN) is naltrexone, an opioid-blocking drug, prescribed at a small fraction of its usual dose for chronic pain and inflammatory conditions. The FDA-approved naltrexone tablet is indicated for alcohol dependence and opioid blockade, so every low-dose use is off-label.1 The best-studied use is fibromyalgia, where one small crossover trial found less pain and two larger trials found no benefit over placebo.3-5 If you are considering it, a physician can weigh it against your medications, liver markers and goals.
What Low-Dose Naltrexone Is
Naltrexone is a pure opioid antagonist, which means it binds opioid receptors and blocks the effects of opioid drugs.1 At its labeled dose it is used in addiction treatment. At a much lower dose it is prescribed for an entirely different purpose.
A 2020 review describes the low-dose effects as distinct from those at the dose approved for alcohol and opioid dependence.2 The same review lists fibromyalgia, inflammatory bowel conditions and multiple sclerosis as the chronic pain conditions where LDN has shown promise.2 Promise in a review is a reason to study a drug. It is a weaker basis than a trial in the condition you have.
If you have read about LDN for one of these conditions, the useful next question is which trials tested it there, and what they found. The strength of evidence differs by condition, so your own reason for asking decides which trials matter to you.
FDA Status and Off-Label Use
The naltrexone tablet label lists two indications: the treatment of alcohol dependence and the blockade of the effects of opioids taken from outside the body.1 No other use appears on the label. The authors of a 2026 fibromyalgia trial state plainly that LDN has been used off-label for fibromyalgia for over a decade.5
Off-label means the FDA has not reviewed LDN for the condition you want to treat. Your physician's job is to match the evidence to your situation and explain that reasoning to you.
The Proposed Mechanism in Pain and Inflammation
The leading explanation for LDN's effect is modulation of neuro-inflammation. A 2020 review describes it as modulation of glial cells, the support cells of the nervous system, and of the inflammatory chemicals they release in the brain and spinal cord.2 The review frames this as how the mechanism "appears" to work, so it remains a proposal under study.
This mechanism is why LDN is often grouped with inflammation-focused care. Chronic low-grade inflammation is its own topic, covered in inflammaging. For your decision, the mechanism matters less than the outcome trials, because a plausible mechanism does not guarantee a result in people.
Fibromyalgia Trial Results
Fibromyalgia has been tested in three randomized LDN trials and one meta-analysis, and their results point in different directions.
A 2013 crossover trial enrolled 31 women with fibromyalgia, and each woman took LDN and placebo in separate phases.3 Pain fell by 28.8% from baseline on LDN versus 18.0% on placebo. Life satisfaction and mood improved, while fatigue and sleep did not.3 The authors called for larger parallel-group trials to settle the question.
Two such trials have since been published:
- Due Bruun 2024: 99 women in Denmark were randomized to LDN or placebo for 12 weeks. LDN was not superior to placebo for pain. The authors reported a possible effect on memory problems and suggested future trials look at it.4
- INNOVA 2026: 98 women were randomized and followed for 12 months. LDN was well tolerated but showed no clinically meaningful benefit over placebo for pain-related outcomes.5
A 2025 meta-analysis pooled eight studies. Pain and symptom severity fell from baseline on LDN, but the reductions were not superior to placebo.6 All three trials enrolled women only, so none of them tells you how men with fibromyalgia respond.
Practical takeaway: the larger fibromyalgia trials found no benefit over placebo. If you and your physician still decide to try LDN, run it as a measured trial against a clear pain score, with an agreed point to stop if the score does not move.
Crohn's Disease and Multiple Sclerosis Evidence
Outside fibromyalgia, the LDN evidence comes from a handful of small trials. Each one gives a narrow signal you can weigh against your own diagnosis.
Crohn's Disease
A 2018 Cochrane review found two randomized studies with 46 participants in total.7 In the adult study, 30% of the LDN group reached clinical remission at 12 weeks versus 18% on placebo, a difference that did not reach statistical significance.7 Clinical response was higher, and this difference reached statistical significance: 83% of the LDN group versus 38% on placebo.7
The Cochrane authors rated the overall evidence as low certainty because the numbers were so small.7 If you have Crohn's disease, LDN is a question for your gastroenterologist alongside your established treatment.
Multiple Sclerosis
A 2010 pilot crossover trial enrolled 80 people with multiple sclerosis, and 60 completed it.8 LDN improved several mental health quality-of-life scores and was well tolerated, with no serious adverse events.8 The authors noted that dropouts and data errors reduced the trial's statistical power.8 The trial measured quality of life, so it says nothing about relapses or disease progression. Any LDN discussion for MS belongs with the neurologist who manages your disease.
Long COVID Research
A 2026 systematic review searched for LDN studies in long COVID and found no randomized controlled trials.9 It pooled four observational before-and-after studies with 155 people. Fatigue, brain fog, sleep, pain and daily functioning improved after LDN.9 The authors rated the certainty of evidence as low. A before-and-after study has no placebo group, so it cannot separate the drug's effect from natural recovery.9
If long COVID symptoms are your reason for asking, a physician can first look for measurable contributors to your fatigue, such as hormones, thyroid function and nutritional deficiencies, before adding an off-label drug.
Safety Record and Label Warnings
Naltrexone has a reassuring overall safety record in trials. A 2019 meta-analysis of 89 randomized trials with 11,194 participants found no increased risk of serious adverse events with naltrexone compared with placebo.10 The result was consistent across different doses and diseases.10 That analysis excluded people using opioids, and naltrexone's main risks concern that group.
The label lists those risks plainly:1
- Opioid use: naltrexone is contraindicated if you take opioid pain medication, depend on opioids, or are in opioid withdrawal.
- Precipitated withdrawal: in someone dependent on opioids, an opioid blocker can trigger withdrawal severe enough to require hospitalization.
- Opioid sensitivity: after naltrexone stops, a person may respond to lower opioid doses than before, which the label warns could cause life-threatening opioid intoxication.
- Liver injury: cases of hepatitis and clinically meaningful liver dysfunction have been reported.
Tell your physician about every pain medication you take, including tramadol and any prescription you use only occasionally. That disclosure lets your physician screen for the main contraindication on the label.
How a Physician Decides Whether LDN Fits You
A physician deciding on LDN starts with your diagnosis, your medication list and your goal. The evidence differs so much by condition that the reason you are asking shapes the whole conversation.
Your physician will check for any opioid use first, because that is the main contraindication.1 Liver markers belong in your baseline labs given the label's hepatotoxicity warning.1 Inflammation markers can add context when the goal is inflammatory, and the biomarker guide explains what a broad panel measures.
You and your physician should agree on what improvement looks like before you start. A pain score, a symptom diary or a repeat lab gives you a fair test. If the measure does not move over the agreed period, stopping is a reasonable outcome, and it frees you to try the next option on your list.
The Opt Take on Low-Dose Naltrexone
LDN is one more tool, and its value depends on the cause of your symptoms. At Opt Health, the starting point is a blood panel of 55+ biomarkers spanning hormones, inflammation, cardiovascular risk and more. Your existing conditions and current medications are reviewed at your initial consultation, so your physician reviews any opioid use before a prescription is considered.
A physician reads your results with you 1:1 and builds a plan around the pattern in your labs. That plan can include prescriptions, peptides and supplements shipped from our pharmacy to your home. Labs and a physician consultation repeat every 3 to 4 months, so a trial of any medication gets judged against your own numbers and symptoms, and your plan is adjusted on what changed.
Get started: Begin with Opt Health, where a physician reads your labs, builds your plan, and adjusts it over the loop.
Frequently Asked Questions
Low-dose naltrexone is prescribed off-label for chronic pain and inflammatory conditions. The conditions with published trials include fibromyalgia, Crohn's disease and multiple sclerosis, with early observational data in long COVID.2,7-9 The evidence differs by condition, so the right question for you is what the trials found for your specific diagnosis.
The proposed mechanism is modulation of glial cells and the inflammatory chemicals they release in the central nervous system.2 That mechanism is still being studied. In fibromyalgia, one small crossover trial found less pain than placebo, and two larger parallel-group trials did not.3-5 Your physician can help you set a clear measure to judge whether it helps your pain.
No. The FDA-approved naltrexone tablet is indicated for alcohol dependence and for blocking the effects of opioids.1 Low-dose use for pain, autoimmune or inflammatory conditions is off-label, which means a prescriber is using the drug outside its labeled indications.5
No. Naltrexone is a pure opioid antagonist, which means it blocks opioid receptors instead of activating them.1 That is why it is contraindicated if you take opioid pain medication. It can block those drugs, and in someone dependent on opioids it can trigger withdrawal.1
The naltrexone label states that it does not lead to physical or psychological dependence, and tolerance to its opioid-blocking effect is not known to occur.1 You can stop it under your prescriber's direction without the dependence concerns that come with opioid medicines.
Across 89 randomized trials, naltrexone did not raise the risk of serious adverse events compared with placebo.10 Fibromyalgia trials of LDN reported similar adverse event rates in the LDN and placebo groups.4,5 The label's main warnings concern opioid use and liver injury.1 Tell your physician about every pain medication you take so your plan accounts for both.
Whether LDN fits depends on your diagnosis, your medications and what your labs show. An Opt Health membership pairs 55+ biomarkers with a 1:1 physician review, then repeats labs and a physician consultation every 3 to 4 months.
References
- SpecGx LLC. Naltrexone hydrochloride tablets, USP. Prescribing information. DailyMed. Revised May 2026. Accessed October 14, 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06ff2d5a-e62b-4fa4-bbdb-01938535bc65
- Kim PS et al. Low-dose naltrexone for chronic pain: update and systemic review. Curr Pain Headache Rep. 2020;24(10):64. https://pubmed.ncbi.nlm.nih.gov/32845365/
- Younger J et al. Low-dose naltrexone for the treatment of fibromyalgia: findings of a small, randomized, double-blind, placebo-controlled, counterbalanced, crossover trial assessing daily pain levels. Arthritis Rheum. 2013;65(2):529-538. https://pubmed.ncbi.nlm.nih.gov/23359310/
- Due Bruun K et al. Naltrexone 6 mg once daily versus placebo in women with fibromyalgia: a randomised, double-blind, placebo-controlled trial. Lancet Rheumatol. 2024;6(1):e31-e39. https://pubmed.ncbi.nlm.nih.gov/38258677/
- Rodríguez-Freire C et al. Efficacy of low-dose naltrexone in women with fibromyalgia syndrome: a 12-month randomised, double-blind, placebo-controlled single-centre clinical trial (INNOVA study). Eur J Pain. 2026;30(6):e70321. https://pubmed.ncbi.nlm.nih.gov/42385209/
- Ologunowa A et al. Efficacy of low-dose naltrexone in treating patients with fibromyalgia: systematic review and meta-analysis. J Pain Palliat Care Pharmacother. 2025;39(3):363-373. https://pubmed.ncbi.nlm.nih.gov/40272382/
- Parker CE et al. Low dose naltrexone for induction of remission in Crohn's disease. Cochrane Database Syst Rev. 2018;4(4):CD010410. https://pubmed.ncbi.nlm.nih.gov/29607497/
- Cree BA et al. Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis. Ann Neurol. 2010;68(2):145-150. https://pubmed.ncbi.nlm.nih.gov/20695007/
- Byambasuren O et al. Effect of low-dose naltrexone for long COVID: a systematic review and meta-analysis. BMJ Open. 2026;16(7):e111253. https://pubmed.ncbi.nlm.nih.gov/42463201/
- Bolton M et al. Serious adverse events reported in placebo randomised controlled trials of oral naltrexone: a systematic review and meta-analysis. BMC Med. 2019;17(1):10. https://pubmed.ncbi.nlm.nih.gov/30642329/
This content is for informational purposes and does not replace evaluation, diagnosis, or treatment by a qualified medical professional.
This article is part of our guide to longevity. See how longevity medicine works at Opt Health.
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