MVIIIHealth The MVIII app
← Back

Research · Medication

Low-dose naltrexone

Fibromyalgia meta-analyses disagree. Two report less pain than placebo, one found no difference, and two newer trials found no difference. In Crohn's disease, one trial of 34 adults found more clinical response and no difference in remission. A long COVID review found no randomized trials. Vivid dreams were more common than on placebo.

Add to Bio HackChecked 2026-11-09
Status
Prescription drug in the US. Naltrexone is FDA-approved at 50 mg a day for alcohol dependence and for blocking the effects of opioids in opioid dependence. Low-dose use, about 1 to 4.5 mg a day, is off-label and not FDA-approved for any condition.
Also called
LDN, low dose naltrexone, naltrexone, naltrexone hydrochloride, ReVia
Taken for
fibromyalgia, chronic pain, Crohn's disease, multiple sclerosis, long COVID, autoimmune conditions, inflammation, joint pain

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help1

Reported risks3

What people take it for, and what was found

Shown to help1

Limited

Long COVID

Limited evidence: fatigue, brain fog, sleep and pain improved from baseline in uncontrolled studies of long COVID. No randomized trials were found.

The numbers and sources
Effect
A 2026 systematic review screened 397 records and found no randomized trials. In 4 pre-post studies (155 people) at 1 to 6 mg a day, fatigue (Hedges' g -0.74, 95% CI -1.11 to -0.37), brain fog (g -0.53), sleep (g -0.60), pain (g -0.93) and daily function (g -0.93) improved from baseline [12].
Population
155 people with long COVID in the US and Ireland in uncontrolled studies [12].
Sources
[12]
Caveats
The review rated certainty as low, and its studies had no control group [12]. No peer-reviewed randomized trial was located.

Mixed results3

Moderate

Fibromyalgia pain

Mixed results: two meta-analyses found less fibromyalgia pain than placebo, while a third and two later trials found no difference.

The numbers and sources
Effect
In 4 RCTs (222 patients), pain scores fell more than on placebo (MD -0.86, 95% CI -1.20 to -0.51, I² 33%), while the revised Fibromyalgia Impact Questionnaire did not differ [1]. A meta-analysis of 5 RCTs found less pain than placebo (SMD -0.61, 95% CI -1.14 to -0.08) and no change in mechanical pain threshold [2]. A third meta-analysis of 8 trials found no difference from placebo in pain (SMD -0.50, 95% CI -1.19 to 0.19, I² 91%) or symptom severity [3]. In a crossover trial of 58 patients, 4.5 mg a day did not differ from placebo in pain ratings or questionnaire scores [4]. In 98 women followed for 12 months, pain at 3 months fell 0.33 points on LDN and 0.64 on placebo (difference 0.49, p 0.236) [5].
Population
Adults with fibromyalgia in small RCTs [1][2][3], 58 patients in a crossover trial with treatment periods of about 3 weeks [4], and 98 women over 12 months [5].
Sources
[1], [2], [3], [4], [5]
Caveats
The meta-analyses reach different answers from overlapping trials. Most trials were crossover designs with fewer than 60 people. The two trials published after the meta-analyses found no difference [4][5].
Limited

Crohn's disease

Small trials found more clinical and endoscopic responses than placebo in Crohn's disease, while remission did not differ significantly. Evidence was rated low quality.

The numbers and sources
Effect
A Cochrane review found 2 RCTs (46 participants). In 34 adults, 4.5 mg a day for 12 weeks led to clinical remission in 30% against 18% on placebo (RR 1.48, 95% CI 0.42 to 5.24). A 70-point clinical response occurred in 83% against 38% (RR 2.22, 95% CI 1.14 to 4.32), and endoscopic response in 72% against 25% (RR 2.89, 95% CI 1.18 to 7.08). Endoscopic remission did not differ significantly [9].
Population
34 adults with active Crohn's disease and 12 children [9].
Sources
[9]
Caveats
The review rated the evidence as low quality because of sparse data and found it insufficient for firm conclusions [9].
Limited

Multiple sclerosis

Small trials found mixed results in multiple sclerosis: one saw better mental health and pain scores, another no difference from placebo.

The numbers and sources
Effect
In a crossover trial of 80 people, 4.5 mg nightly for 8 weeks raised the SF-36 mental component score by 3.3 points (p 0.04) and the Mental Health Inventory by 6 points (p < 0.01), and improved pain effects by 1.6 points (p 0.04) [10]. In a 17-week crossover trial of 96 people, pain, energy, emotional well-being, cognitive function and overall quality of life did not differ from placebo [11].
Population
Adults with relapsing-remitting or secondary progressive multiple sclerosis, 80 at one center [10] and 96 at two universities [11].
Sources
[10], [11]
Caveats
Only 60 of 80 completed the first trial, and its authors state dropouts and data errors cut its statistical power [10]. Neither trial measured relapses or disability as a main outcome.

Not shown to help2

Moderate

Chronic pain across conditions

Not shown to improve pain or quality of life across chronic pain conditions, with less pain than placebo only in fibromyalgia in one analysis.

The numbers and sources
Effect
In a meta-analysis of 7 RCTs, pain response did not differ from control overall (d -0.11, 95% CI -0.96 to 0.74). Against placebo in fibromyalgia, pain was lower (d -0.34, 95% CI -0.62 to -0.06). Against active drugs, there was no difference [6]. A systematic review of 7 RCTs (406 patients) at 2 to 4.5 mg a day found no improvement in pain or quality of life across chronic pain conditions [7]. In 23 people with osteoarthritis or inflammatory arthritis, 8 weeks of 4.5 mg did not change pain interference (-23 points against -22 on placebo, p 0.90), pain severity or fatigue [8].
Population
Adults with chronic pain conditions, including fibromyalgia [6][7], and 17 people with osteoarthritis and 6 with inflammatory arthritis [8].
Sources
[6], [7], [8]
Caveats
The arthritis trial was a pilot too small to rule out a modest effect [8].
Limited

Other autoimmune conditions

One trial found no change in disease activity over placebo in lichen planopilaris, a scarring hair loss. No trials in other autoimmune conditions were located.

The numbers and sources
Effect
In 34 patients with lichen planopilaris, an autoimmune scarring hair loss, 3 mg a day added to clobetasol cream for 6 months did not change disease activity more than placebo with clobetasol (p 0.813) [13].
Population
34 patients analyzed by intention to treat [13].
Sources
[13]
Caveats
One small trial in one condition. No controlled trials in lupus, rheumatoid arthritis, psoriasis or thyroid disease were located.

Doses studied

Most trials gave 4.5 mg once a day, often at night, for 8 to 16 weeks [4][5][9][10]. The lichen planopilaris trial used 3 mg [13], the pediatric Crohn's trial used 0.1 mg/kg up to 4.5 mg [9], and the long COVID studies used 1 to 6 mg [12]. The FDA label dose for alcohol and opioid dependence is 50 mg once a day [14].

Risks

Reported risks3

ModerateVery common

Adverse events in trials

Shown to raise vivid dreams about 2.4 times over placebo, with adverse events overall 1.4 times as frequent. Serious adverse events did not differ.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
Vivid dreams were more common on LDN than placebo (RR 2.41, 95% CI 1.77 to 3.28), and headache did not differ [2]. Another meta-analysis found more vivid dreams and nausea, with no difference in serious adverse events, headache, diarrhea or dizziness [1]. Across chronic pain trials, adverse events were 1.4 times as frequent as on placebo (IRR 1.4, 95% CI 1.12 to 1.75) [6]. In the 12-month trial, adverse events occurred in 68.8% on LDN and 72% on placebo, with no treatment-related serious events [5]. In Crohn's disease, withdrawals and specific adverse events did not differ [9].
Population
Trial participants with fibromyalgia, chronic pain, Crohn's disease [1][2][5][6][9].
Sources
[1], [2], [5], [6], [9]
Caveats
Most trials were small and lasted under 4 months.
LimitedVery common

Liver enzymes at high doses

The label reports raised liver enzymes in 19% at 300 mg a day against 0% on placebo, a dose more than 60 times a low dose.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
The label reports that at 300 mg a day, 19% (5 of 26) of naltrexone recipients and 0% (0 of 24) on placebo developed raised liver enzymes after 3 to 8 weeks. It lists cases of hepatitis and liver dysfunction from clinical development and postmarketing reports [14].
Population
Placebo-controlled studies at up to 300 mg a day, summarized in the label [14].
Sources
[14]
Caveats
300 mg is more than 60 times a 4.5 mg low dose. The label notes other causes were often present when liver enzymes rose [14].
LimitedHow often is not known

Opioid withdrawal and opioid sensitivity

The 50 mg label warns people on opioids may have severe withdrawal, and after stopping may respond to lower opioid doses, with fatal overdoses reported.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The naltrexone label lists people receiving opioid pain medicines or dependent on opioids as contraindicated. It states withdrawal brought on by an opioid blocker can be severe enough to need hospitalization, with symptoms within 5 minutes lasting up to 48 hours. It also states that after stopping, people may respond to lower opioid doses than before, and fatal overdoses have been reported [14].
Population
Label for 50 mg tablets in alcohol and opioid dependence [14].
Sources
[14]
Caveats
The label describes 50 mg use. The LDN trials above did not report on opioid interactions.

Claims tested and not found

  1. That LDN lowers fibromyalgia pain more than placebo. Two trials, of 58 people over 3 weeks and 98 women over 12 months, found no difference [4][5], and one meta-analysis found none [3].
  2. That LDN reduces chronic pain across conditions. Pain response did not differ from control across 7 RCTs [6].
  3. That LDN improves quality of life in multiple sclerosis. A 17-week trial of 96 people found no difference from placebo [11].
  4. That LDN puts active Crohn's disease into remission. Clinical remission at 12 weeks did not differ significantly from placebo [9].

Sources

  1. Vatvani AD, Patel P, Hariyanto TI, Yanto TA. Efficacy and safety of low-dose naltrexone for the management of fibromyalgia: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis. The Korean Journal of Pain. 2024. https://doi.org/10.3344/kjp.24202
  2. Nazir MH, Mehboob U, Farhan M, et al. Efficacy and safety of low-dose naltrexone (LDN) in fibromyalgia: a systematic review and meta-analysis. Annals of Medicine and Surgery. 2025. https://doi.org/10.1097/MS9.0000000000003203
  3. Ologunowa A, Otoo MN, Caffrey AR, et al. Efficacy of Low-Dose Naltrexone in Treating Patients with Fibromyalgia: systematic Review and Meta-Analysis. Journal of Pain and Palliative Care Pharmacotherapy. 2025. https://doi.org/10.1080/15360288.2025.2496526
  4. Bested K, Jensen LM, Andresen T, et al. Low-dose naltrexone for treatment of pain in patients with fibromyalgia: a randomized, double-blind, placebo-controlled, crossover study. Pain Reports. 2023. https://doi.org/10.1097/PR9.0000000000001080
  5. Rodríguez-Freire C, Navarrete J, Rozadilla-Sacanell A, 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). European Journal of Pain. 2026. https://doi.org/10.1002/ejp.70321
  6. Hegde NC, Mishra A, V D, et al. Low Dose Naltrexone In The Management Of Chronic Pain Syndrome: A Meta-Analysis Of Randomized Controlled Clinical Trials. Current Pain and Headache Reports. 2025. https://doi.org/10.1007/s11916-025-01411-1
  7. Rassi-Mariani V, Barreto ESR, Antunes CR, et al. The use of naltrexone in the treatment of chronic pain: a systematic review. Pain Management. 2024. https://doi.org/10.1080/17581869.2024.2401769
  8. Beaudette-Zlatanova B, Lew RA, Otis JD, et al. Pilot Study of Low-dose Naltrexone for the Treatment of Chronic Pain Due to Arthritis: A Randomized, Double-blind, Placebo-controlled, Crossover Clinical Trial. Clinical Therapeutics. 2023. https://doi.org/10.1016/j.clinthera.2023.03.013
  9. Parker CE, Nguyen TM, Segal D, et al. Low dose naltrexone for induction of remission in Crohn's disease. Cochrane Database of Systematic Reviews. 2018. https://doi.org/10.1002/14651858.CD010410.pub3
  10. Cree BA, Kornyeyeva E, Goodin DS. Pilot trial of low-dose naltrexone and quality of life in multiple sclerosis. Annals of Neurology. 2010. https://doi.org/10.1002/ana.22006
  11. Sharafaddinzadeh N, Moghtaderi A, Kashipazha D, et al. The effect of low-dose naltrexone on quality of life of patients with multiple sclerosis: a randomized placebo-controlled trial. Multiple Sclerosis Journal. 2010. https://doi.org/10.1177/1352458510366857
  12. Byambasuren O, Atkins T, Baptista S, et al. Effect of low-dose naltrexone for long COVID: a systematic review and meta-analysis. BMJ Open. 2026. https://doi.org/10.1136/bmjopen-2025-111253
  13. Lajevardi V, Salarvand F, Ghiasi M, et al. The efficacy and safety of oral low dose naltrexone versus placebo in the patients with lichen planopilaris: a randomized controlled clinical trial. Journal of Dermatological Treatment. 2022. https://doi.org/10.1080/09546634.2020.1774488
  14. U.S. Food and Drug Administration. Naltrexone hydrochloride tablets, USP, prescribing information (SpecGx LLC). 2026. DailyMed. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=06ff2d5a-e62b-4fa4-bbdb-01938535bc65

Everything in the library