Low-dose naltrexone

updated

Low-dose naltrexone (LDN) is naltrexone, an FDA-approved drug for alcohol dependence and opioid blockade, taken off label at 4.5 to 6 mg a day for fibromyalgia, autoimmune conditions and mood. The low-dose trials are mostly null: one 31-woman fibromyalgia trial was positive, but larger and longer fibromyalgia trials, a multiple sclerosis trial and a depression trial found no meaningful benefit over placebo. The A reflects the approved drug, not the low-dose claims.

Opioid receptor antagonist

  • LDN is the same molecule as the approved naltrexone tablets, given at 4.5 or 6 mg a day in the trials reviewed.
  • FDA first approved oral naltrexone as REVIA on 20 November 1984; the current tablet label covers alcohol dependence and opioid blockade only.
  • No FDA application lists a single-ingredient naltrexone product below 25 mg.
  • In fibromyalgia, a 31-woman crossover trial was positive, but parallel trials in 99 and 98 women found no meaningful pain benefit over placebo.
  • A depression trial in 37 adults and a multiple sclerosis trial in 96 people found no difference from placebo.
  • The label's liver and withdrawal warnings describe 50 mg and higher doses, not LDN.

What is low-dose naltrexone, and is it approved?

LDN is naltrexone taken at a few milligrams a day, not a separate molecule. FDA approved naltrexone tablets in 1984, and the current label covers alcohol dependence and opioid blockade; no application covers fibromyalgia, autoimmune disease or mood, and none lists a single-ingredient product below 25 mg.

Naltrexone free base is PubChem CID 5360515, C20H23NO4, 341.4 g/mol, CAS 16590-41-3. The approved tablets contain naltrexone hydrochloride, CID 5485201, C20H24ClNO4, 377.9 g/mol, CAS 16676-29-2. The trials on this page gave 4.5 mg or 6 mg a day. Their abstracts say naltrexone without stating whether the dose is expressed as the salt or the free base, and whether a compounded LDN product matches a trial formulation is not established.

FDA first approved oral naltrexone as REVIA under NDA 018932 on 20 November 1984, and the record now marks it discontinued. Generic tablets followed from 1998, for example ANDA 074918 on 8 May 1998. Related applications are VIVITROL, an extended-release injection (NDA 021897, 13 April 2006), and CONTRAVE, naltrexone with bupropion (NDA 200063, 10 September 2014).

The single-ingredient tablets in the FDA records are 50 mg, with 25 mg and 100 mg strengths added for one generic (ANDA 076264); no application lists a single-ingredient product below 25 mg. The SpecGx tablet label (version effective 4 September 2026) covers alcohol dependence and blockade of the effects of exogenously administered opioids, with no indication for pain, fibromyalgia, autoimmune disease or mood.

PubChem: naltrexone and naltrexone hydrochloride identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 5360515 (naltrexone) and CID 5485201 (naltrexone hydrochloride).

Naltrexone free base: C20H23NO4, 341.4 g/mol, CAS 16590-41-3. Naltrexone hydrochloride, the salt in the approved tablets: C20H24ClNO4, 377.9 g/mol, CAS 16676-29-2. LDN is not a separate molecule.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule and salt
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Trial abstracts do not say whether doses are expressed as the salt or the free base.

Read the original source
Drugs@FDA: naltrexone approvals, 1984 to 2014

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 018932 (REVIA), with related applications ANDA 074918, ANDA 076264, NDA 021897 (VIVITROL) and NDA 200063 (CONTRAVE). Dates read from the openFDA Drugs@FDA records on 11 October 2026.

FDA first approved oral naltrexone as REVIA under NDA 018932 on 20 November 1984 (marked discontinued). Generic tablets followed from 1998 (ANDA 074918, 8 May 1998). VIVITROL (NDA 021897) was approved on 13 April 2006 and CONTRAVE (NDA 200063) on 10 September 2014. Single-ingredient tablets are 50 mg, with 25 mg and 100 mg strengths for one generic (ANDA 076264); no application lists a single-ingredient product below 25 mg, and none covers fibromyalgia, autoimmune disease or mood.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1984 to 2014
Study design
FDA application records
Funding
not stated in the source

These records give approval dates and strengths. Indications come from the tablet label.

Read the original source
Naltrexone tablet label, version effective 4 September 2026: indication, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Naltrexone hydrochloride film-coated oral tablets, 50 mg (SpecGx), prescribing information, label version effective 4 September 2026. Set ID 06ff2d5a-e62b-4fa4-bbdb-01938535bc65.

The label covers alcohol dependence and blockade of the effects of exogenously administered opioids, with no indication for pain, fibromyalgia, autoimmune disease or mood. It contraindicates naltrexone in patients receiving opioid analgesics and in those currently dependent on opioids, and warns it can precipitate withdrawal. It reports hepatitis and clinically significant liver dysfunction; doses above the recommended range (up to 300 mg per day in studies) caused hepatocellular injury in a substantial proportion of patients, and single doses above 50 mg carry a higher risk. Oral bioavailability is estimated at 5 to 40%, with half-lives of 4 hours for naltrexone and 13 hours for 6-beta-naltrexol.

Participants / model
Adults with alcohol dependence or opioid dependence; label PK participants
Treatment
Naltrexone hydrochloride film-coated oral tablets, 50 mg
Follow-up
Label version effective 4 September 2026
Study design
FDA prescribing information
Funding
not stated in the source

The PK and safety statements describe 50 mg and higher doses, not LDN.

Read the original source

What did the fibromyalgia trials find?

One small crossover trial in 31 women found less pain on LDN than placebo. Two larger parallel-group trials, in 99 women for 12 weeks and 98 women for 12 months, found no meaningful pain benefit over placebo.

In a randomized, double-blind, counterbalanced crossover trial, 31 women with fibromyalgia took naltrexone 4.5 mg a day or placebo. Pain fell 28.8% from baseline on naltrexone versus 18.0% on placebo (P = 0.016). Satisfaction with life (P = 0.045) and mood (P = 0.039) improved, but fatigue and sleep did not. A response, defined as a significant pain reduction plus a significant reduction in fatigue or sleep problems, occurred in 32% versus 11% (P = 0.05). The title calls the trial small, and the authors call for parallel-group trials.

In a single-centre Danish trial (NCT04270877), 99 women were randomized to naltrexone 6 mg a day (n=49) or placebo (n=50) for 12 weeks. Pain intensity on a 0 to 10 scale changed -1.3 (95% CI -1.7 to -0.8) with naltrexone and -0.9 (-1.4 to -0.5) with placebo, a between-group difference of -0.34 (-0.95 to 0.27; p=0.27). The authors concluded it was not shown to be superior to placebo for pain.

In the INNOVA trial, 98 women were randomized to naltrexone 4.5 mg a day (n=48) or placebo (n=50) for 12 months. At 3 months, pain intensity changed -0.33 points with naltrexone and -0.64 with placebo, an adjusted between-group difference of 0.49 (p = 0.236, d = 0.19). Secondary outcomes at 3, 6 and 12 months showed minor and inconsistent changes, and the authors found no clinically meaningful benefit over placebo.

Crossover trial: 31 women, pain down 28.8% versus 18.0%

Randomized controlled trial

Younger J et al. Arthritis Rheum. 2013;65(2):529-38. PMID 23359310.

Pain fell 28.8% from baseline on naltrexone versus 18.0% on placebo (P = 0.016). Satisfaction with life (P = 0.045) and mood (P = 0.039) improved; fatigue and sleep did not. Response occurred in 32% versus 11% (P = 0.05). Tolerability matched placebo and no serious side effects were reported.

Participants / model
31 women with fibromyalgia
Treatment
Oral naltrexone 4.5 mg a day or placebo
Follow-up
not stated in the source
Study design
Randomized, double-blind, counterbalanced crossover trial
Funding
not stated in the source

The title calls the trial small, and the authors call for parallel-group trials.

Read the original source
Danish trial: 99 women, 12 weeks, no significant pain difference

Randomized controlled trial

Due Bruun K et al. Lancet Rheumatol. 2024;6(1):e31-e39. PMID 38258677.

Pain intensity (0 to 10) changed -1.3 (95% CI -1.7 to -0.8) with naltrexone and -0.9 (-1.4 to -0.5) with placebo; between-group difference -0.34 (-0.95 to 0.27; p=0.27). Adverse events occurred in 41 of 49 (84%) versus 43 of 50 (86%), and 4 (8%) versus 3 (6%) stopped for adverse events. Not shown superior to placebo for pain.

Participants / model
99 women with fibromyalgia
Treatment
Oral naltrexone 6 mg a day (n=49) or placebo (n=50)
Follow-up
12 weeks
Study design
Single-centre randomized trial (NCT04270877)
Funding
not stated in the source

The authors suggested testing an effect on memory problems.

Read the original source
INNOVA: 98 women, 12 months, no meaningful benefit

Randomized controlled trial

Rodríguez-Freire C et al. Eur J Pain. 2026;30(6):e70321. PMID 42385209.

At 3 months, pain intensity changed -0.33 points with naltrexone and -0.64 with placebo, an adjusted between-group difference of 0.49 (p = 0.236, d = 0.19). Secondary outcomes at 3, 6 and 12 months showed minor and inconsistent changes. Adverse events were reported by 33 (68.8%) on naltrexone and 36 (72%) on placebo, with no treatment-related serious events.

Participants / model
98 women with fibromyalgia
Treatment
Oral naltrexone 4.5 mg a day (n=48) or placebo (n=50)
Follow-up
12 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The authors concluded LDN was well tolerated but gave no clinically meaningful benefit over placebo.

Read the original source

Why is the 2024 fibromyalgia meta-analysis disputed?

A 2024 meta-analysis of 4 trials in 222 patients reported lower pain scores with LDN, but it has a published corrigendum and a letter from authors of the Danish trial saying it inflated their responder counts. Their re-analysis found no significant difference from placebo, and the meta-analysis predates the 12-month INNOVA trial.

The meta-analysis pooled 4 randomized trials in 222 patients and reported lower pain scores with LDN than placebo (mean difference -0.86, 95% CI -1.20 to -0.51) and a higher pressure pain threshold. It found no difference on the revised Fibromyalgia Impact Questionnaire, more vivid dreams and nausea, and no difference in serious adverse events.

A corrigendum was later published (PMID 41469220); its content is not described here. In a letter in the same journal (PMID 41469218), authors of the Danish trial reported that the meta-analysis listed their responders as 32 of 49 and 20 of 50, where their publication supports 20 of 49 and 13 of 50. They also said it pooled different pain scales as raw mean differences and handled crossover data inconsistently. Their re-analysis found no significant difference between LDN and placebo, with a standardized mean difference of -0.25 (95% CI -0.59 to 0.09) in the 12-week studies. The letter's authors disclose having published an LDN trial.

2024 meta-analysis: 4 trials, 222 patients; corrigendum and disputing letter

Systematic review and meta-analysis

Vatvani AD et al. Korean J Pain. 2024;37(4):367-378. PMID 39344363.

Lower pain scores with LDN than placebo (mean difference -0.86, 95% CI -1.20 to -0.51) and a higher pressure pain threshold; no difference on the revised Fibromyalgia Impact Questionnaire; more vivid dreams and nausea; no difference in serious adverse events. A later letter by authors of the Danish trial reported inflated responder counts, pooling of different pain scales as raw mean differences and inconsistent handling of crossover data, and their re-analysis found no significant difference (standardized mean difference -0.25, 95% CI -0.59 to 0.09, in the 12-week studies).

Participants / model
Patients with fibromyalgia in 4 pooled randomized trials (222 patients)
Treatment
Oral LDN versus placebo
Follow-up
Pooled trials
Study design
Meta-analysis of randomized trials, with a published corrigendum and a disputing letter
Funding
not stated in the source

The corrigendum's content is not described here. The letter's authors disclose having published an LDN trial. The meta-analysis predates the INNOVA trial.

Read the original source
Danish trial: 99 women, 12 weeks, no significant pain difference

Randomized controlled trial

Due Bruun K et al. Lancet Rheumatol. 2024;6(1):e31-e39. PMID 38258677.

Pain intensity (0 to 10) changed -1.3 (95% CI -1.7 to -0.8) with naltrexone and -0.9 (-1.4 to -0.5) with placebo; between-group difference -0.34 (-0.95 to 0.27; p=0.27). Adverse events occurred in 41 of 49 (84%) versus 43 of 50 (86%), and 4 (8%) versus 3 (6%) stopped for adverse events. Not shown superior to placebo for pain.

Participants / model
99 women with fibromyalgia
Treatment
Oral naltrexone 6 mg a day (n=49) or placebo (n=50)
Follow-up
12 weeks
Study design
Single-centre randomized trial (NCT04270877)
Funding
not stated in the source

The authors suggested testing an effect on memory problems.

Read the original source

What did studies in Crohn's disease, multiple sclerosis and depression find?

A Cochrane review of 2 Crohn's disease trials with 46 participants found better clinical and endoscopic response but no significant difference in remission, and rated the evidence low quality. A multiple sclerosis trial in 96 people and a depression trial in 37 adults found no meaningful difference from placebo.

The Cochrane review found 2 randomized trials: 12 weeks of 4.5 mg a day in 34 adults and 8 weeks of 0.1 mg/kg a day (maximum 4.5 mg) in 12 children. In adults, clinical remission was 30% (5 of 18) versus 18% (3 of 16) on placebo (RR 1.48, 95% CI 0.42 to 5.24, not significant). A 70-point clinical response was 83% (15 of 18) versus 38% (6 of 16) (RR 2.22, 1.14 to 4.32), and endoscopic response 72% (13 of 18) versus 25% (4 of 16) (RR 2.89, 1.18 to 7.08). The evidence was rated low quality because of serious imprecision, and the authors found it insufficient for firm conclusions.

A 17-week randomized, double-blind, placebo-controlled trial in 96 people aged 15 to 65 with relapsing-remitting or secondary progressive multiple sclerosis found no meaningful difference between LDN and placebo on pain, energy, emotional well-being, social, cognitive or sexual function, role limitations, health distress or overall quality of life. Health perception scores differed between groups at baseline, mid-study and the end. The abstract does not state the dose.

Thirty-seven adults with major depressive disorder and moderate symptoms who were taking antidepressants were randomized to LDN (up to 4.5 mg a day) or placebo for 12 weeks (ACTRN12622000881730). MADRS scores fell 10.5 (SD 5.6) with LDN and 9.8 (SD 5.9) with placebo (p = 0.97). LDN did not change high-sensitivity C-reactive protein or exploratory measures of depression, behavioral activation, quality of life, sickness symptoms or mood.

Cochrane review: 2 trials, 46 participants, low-quality evidence

Systematic review and meta-analysis

Parker CE et al. Cochrane Database Syst Rev. 2018;4(4):CD010410. PMID 29607497.

In adults, clinical remission was 30% (5 of 18) versus 18% (3 of 16) on placebo (RR 1.48, 95% CI 0.42 to 5.24, not significant); 70-point clinical response 83% (15 of 18) versus 38% (6 of 16) (RR 2.22, 1.14 to 4.32); endoscopic response 72% (13 of 18) versus 25% (4 of 16) (RR 2.89, 1.18 to 7.08). Adverse events did not differ and no serious adverse events were reported. Evidence rated low quality because of serious imprecision and insufficient for firm conclusions.

Participants / model
34 adults and 12 children with active Crohn's disease
Treatment
Oral LDN 4.5 mg a day (adults); 0.1 mg/kg a day up to 4.5 mg (children)
Follow-up
12 weeks (adults) and 8 weeks (children)
Study design
Cochrane systematic review of 2 randomized trials
Funding
not stated in the source

Two small trials; the review rated the evidence low quality.

Read the original source
MS trial: 96 people, 17 weeks, no meaningful difference

Randomized controlled trial

Sharafaddinzadeh N et al. Mult Scler. 2010;16(8):964-9. PMID 20534644.

No meaningful difference between LDN and placebo on pain, energy, emotional well-being, social, cognitive or sexual function, role limitations, health distress or overall quality of life (MSQoL-54). Health perception scores differed between groups at baseline, mid-study and the end. The authors called LDN relatively safe but its efficacy under question.

Participants / model
96 people aged 15 to 65 with relapsing-remitting or secondary progressive multiple sclerosis
Treatment
Oral LDN or placebo; dose not stated in the abstract
Follow-up
17 weeks
Study design
Randomized, double-blind, placebo-controlled trial (crossover design per the abstract)
Funding
not stated in the source

Quality-of-life outcomes only.

Read the original source
Depression trial: 37 adults, 12 weeks, no difference (p = 0.97)

Randomized controlled trial

Moloney BD et al. Front Pharmacol. 2026;17:1767654. PMID 41868116.

MADRS scores fell 10.5 (SD 5.6) with LDN and 9.8 (SD 5.9) with placebo, with no difference between groups (p = 0.97). LDN did not change high-sensitivity C-reactive protein or exploratory measures of depression, behavioral activation, quality of life, sickness symptoms or mood.

Participants / model
37 adults with major depressive disorder and moderate symptoms taking antidepressants
Treatment
Oral LDN up to 4.5 mg a day or placebo, added to antidepressants
Follow-up
12 weeks
Study design
Randomized placebo-controlled trial (ACTRN12622000881730)
Funding
not stated in the source

The one randomized mood trial reviewed for this page.

Read the original source

Does low-dose naltrexone help fibromyalgia, autoimmune conditions or mood?

Not on the larger trials. Fibromyalgia benefit is not supported by the larger and longer trials, autoimmune benefit rests on a Cochrane review of 46 people rated low quality, and mood benefit is not supported by the one randomized depression trial reviewed.

Sellers promote naltrexone at a few milligrams a day for fibromyalgia, autoimmune conditions and mood. The only positive fibromyalgia trial had 31 women in a crossover design; the parallel-group trials in 99 and 98 women were null. In Crohn's disease, 2 small trials showed better response but not remission, with evidence rated low quality. In multiple sclerosis and in depression added to antidepressants, LDN did not differ from placebo.

These are off-label uses: no FDA application covers low-dose naltrexone or any of these conditions.

Crossover trial: 31 women, pain down 28.8% versus 18.0%

Randomized controlled trial

Younger J et al. Arthritis Rheum. 2013;65(2):529-38. PMID 23359310.

Pain fell 28.8% from baseline on naltrexone versus 18.0% on placebo (P = 0.016). Satisfaction with life (P = 0.045) and mood (P = 0.039) improved; fatigue and sleep did not. Response occurred in 32% versus 11% (P = 0.05). Tolerability matched placebo and no serious side effects were reported.

Participants / model
31 women with fibromyalgia
Treatment
Oral naltrexone 4.5 mg a day or placebo
Follow-up
not stated in the source
Study design
Randomized, double-blind, counterbalanced crossover trial
Funding
not stated in the source

The title calls the trial small, and the authors call for parallel-group trials.

Read the original source
Danish trial: 99 women, 12 weeks, no significant pain difference

Randomized controlled trial

Due Bruun K et al. Lancet Rheumatol. 2024;6(1):e31-e39. PMID 38258677.

Pain intensity (0 to 10) changed -1.3 (95% CI -1.7 to -0.8) with naltrexone and -0.9 (-1.4 to -0.5) with placebo; between-group difference -0.34 (-0.95 to 0.27; p=0.27). Adverse events occurred in 41 of 49 (84%) versus 43 of 50 (86%), and 4 (8%) versus 3 (6%) stopped for adverse events. Not shown superior to placebo for pain.

Participants / model
99 women with fibromyalgia
Treatment
Oral naltrexone 6 mg a day (n=49) or placebo (n=50)
Follow-up
12 weeks
Study design
Single-centre randomized trial (NCT04270877)
Funding
not stated in the source

The authors suggested testing an effect on memory problems.

Read the original source
INNOVA: 98 women, 12 months, no meaningful benefit

Randomized controlled trial

Rodríguez-Freire C et al. Eur J Pain. 2026;30(6):e70321. PMID 42385209.

At 3 months, pain intensity changed -0.33 points with naltrexone and -0.64 with placebo, an adjusted between-group difference of 0.49 (p = 0.236, d = 0.19). Secondary outcomes at 3, 6 and 12 months showed minor and inconsistent changes. Adverse events were reported by 33 (68.8%) on naltrexone and 36 (72%) on placebo, with no treatment-related serious events.

Participants / model
98 women with fibromyalgia
Treatment
Oral naltrexone 4.5 mg a day (n=48) or placebo (n=50)
Follow-up
12 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The authors concluded LDN was well tolerated but gave no clinically meaningful benefit over placebo.

Read the original source
Cochrane review: 2 trials, 46 participants, low-quality evidence

Systematic review and meta-analysis

Parker CE et al. Cochrane Database Syst Rev. 2018;4(4):CD010410. PMID 29607497.

In adults, clinical remission was 30% (5 of 18) versus 18% (3 of 16) on placebo (RR 1.48, 95% CI 0.42 to 5.24, not significant); 70-point clinical response 83% (15 of 18) versus 38% (6 of 16) (RR 2.22, 1.14 to 4.32); endoscopic response 72% (13 of 18) versus 25% (4 of 16) (RR 2.89, 1.18 to 7.08). Adverse events did not differ and no serious adverse events were reported. Evidence rated low quality because of serious imprecision and insufficient for firm conclusions.

Participants / model
34 adults and 12 children with active Crohn's disease
Treatment
Oral LDN 4.5 mg a day (adults); 0.1 mg/kg a day up to 4.5 mg (children)
Follow-up
12 weeks (adults) and 8 weeks (children)
Study design
Cochrane systematic review of 2 randomized trials
Funding
not stated in the source

Two small trials; the review rated the evidence low quality.

Read the original source
MS trial: 96 people, 17 weeks, no meaningful difference

Randomized controlled trial

Sharafaddinzadeh N et al. Mult Scler. 2010;16(8):964-9. PMID 20534644.

No meaningful difference between LDN and placebo on pain, energy, emotional well-being, social, cognitive or sexual function, role limitations, health distress or overall quality of life (MSQoL-54). Health perception scores differed between groups at baseline, mid-study and the end. The authors called LDN relatively safe but its efficacy under question.

Participants / model
96 people aged 15 to 65 with relapsing-remitting or secondary progressive multiple sclerosis
Treatment
Oral LDN or placebo; dose not stated in the abstract
Follow-up
17 weeks
Study design
Randomized, double-blind, placebo-controlled trial (crossover design per the abstract)
Funding
not stated in the source

Quality-of-life outcomes only.

Read the original source
Depression trial: 37 adults, 12 weeks, no difference (p = 0.97)

Randomized controlled trial

Moloney BD et al. Front Pharmacol. 2026;17:1767654. PMID 41868116.

MADRS scores fell 10.5 (SD 5.6) with LDN and 9.8 (SD 5.9) with placebo, with no difference between groups (p = 0.97). LDN did not change high-sensitivity C-reactive protein or exploratory measures of depression, behavioral activation, quality of life, sickness symptoms or mood.

Participants / model
37 adults with major depressive disorder and moderate symptoms taking antidepressants
Treatment
Oral LDN up to 4.5 mg a day or placebo, added to antidepressants
Follow-up
12 weeks
Study design
Randomized placebo-controlled trial (ACTRN12622000881730)
Funding
not stated in the source

The one randomized mood trial reviewed for this page.

Read the original source
Drugs@FDA: naltrexone approvals, 1984 to 2014

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 018932 (REVIA), with related applications ANDA 074918, ANDA 076264, NDA 021897 (VIVITROL) and NDA 200063 (CONTRAVE). Dates read from the openFDA Drugs@FDA records on 11 October 2026.

FDA first approved oral naltrexone as REVIA under NDA 018932 on 20 November 1984 (marked discontinued). Generic tablets followed from 1998 (ANDA 074918, 8 May 1998). VIVITROL (NDA 021897) was approved on 13 April 2006 and CONTRAVE (NDA 200063) on 10 September 2014. Single-ingredient tablets are 50 mg, with 25 mg and 100 mg strengths for one generic (ANDA 076264); no application lists a single-ingredient product below 25 mg, and none covers fibromyalgia, autoimmune disease or mood.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1984 to 2014
Study design
FDA application records
Funding
not stated in the source

These records give approval dates and strengths. Indications come from the tablet label.

Read the original source

How does naltrexone act in the body?

Naltrexone blocks the effects of opioids, which is its labeled use. The sources reviewed give no tested mechanism for a benefit at low doses, and the label's absorption and half-life figures describe 50 mg tablets, not LDN.

The tablet label covers blockade of the effects of exogenously administered opioids and contraindicates naltrexone in people taking opioid analgesics or dependent on opioids. No source reviewed here tests how a dose of 4.5 or 6 mg would produce the benefits claimed for it.

At label doses, oral bioavailability is estimated at 5 to 40% because of first-pass metabolism, and the half-lives are 4 hours for naltrexone and 13 hours for its metabolite 6-beta-naltrexol. These figures describe 50 mg tablets and were not measured at low doses.

Naltrexone tablet label, version effective 4 September 2026: indication, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Naltrexone hydrochloride film-coated oral tablets, 50 mg (SpecGx), prescribing information, label version effective 4 September 2026. Set ID 06ff2d5a-e62b-4fa4-bbdb-01938535bc65.

The label covers alcohol dependence and blockade of the effects of exogenously administered opioids, with no indication for pain, fibromyalgia, autoimmune disease or mood. It contraindicates naltrexone in patients receiving opioid analgesics and in those currently dependent on opioids, and warns it can precipitate withdrawal. It reports hepatitis and clinically significant liver dysfunction; doses above the recommended range (up to 300 mg per day in studies) caused hepatocellular injury in a substantial proportion of patients, and single doses above 50 mg carry a higher risk. Oral bioavailability is estimated at 5 to 40%, with half-lives of 4 hours for naltrexone and 13 hours for 6-beta-naltrexol.

Participants / model
Adults with alcohol dependence or opioid dependence; label PK participants
Treatment
Naltrexone hydrochloride film-coated oral tablets, 50 mg
Follow-up
Label version effective 4 September 2026
Study design
FDA prescribing information
Funding
not stated in the source

The PK and safety statements describe 50 mg and higher doses, not LDN.

Read the original source

What safety warnings apply, and do they cover low doses?

The label contraindicates naltrexone with opioid analgesics or current opioid dependence, warns it can precipitate withdrawal, and reports liver injury, but these warnings describe 50 mg and higher doses, not LDN. In the low-dose trials, adverse events were about as common as on placebo.

The label contraindicates naltrexone in patients receiving opioid analgesics and in those currently dependent on opioids, and warns that it can precipitate withdrawal. It reports cases of hepatitis and clinically significant liver dysfunction, says doses above the recommended range (up to 300 mg a day in studies) caused hepatocellular injury in a substantial proportion of patients, and says single doses above 50 mg carry a higher risk. These are 50 mg and higher-dose data, not LDN data.

In the Danish fibromyalgia trial, adverse events occurred in 41 of 49 (84%) on naltrexone versus 43 of 50 (86%) on placebo, and 4 (8%) versus 3 (6%) stopped for adverse events. In INNOVA, adverse events were reported by 33 (68.8%) on naltrexone and 36 (72%) on placebo, with no treatment-related serious events. In the 31-woman crossover trial, tolerability matched placebo with no serious side effects reported. The 2024 meta-analysis reported more vivid dreams and nausea with LDN and no difference in serious adverse events, and the Crohn's review found no difference in adverse events.

No source on the quality or content of compounded LDN capsules was reviewed, so whether a given product matches a trial formulation is not established.

Naltrexone tablet label, version effective 4 September 2026: indication, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Naltrexone hydrochloride film-coated oral tablets, 50 mg (SpecGx), prescribing information, label version effective 4 September 2026. Set ID 06ff2d5a-e62b-4fa4-bbdb-01938535bc65.

The label covers alcohol dependence and blockade of the effects of exogenously administered opioids, with no indication for pain, fibromyalgia, autoimmune disease or mood. It contraindicates naltrexone in patients receiving opioid analgesics and in those currently dependent on opioids, and warns it can precipitate withdrawal. It reports hepatitis and clinically significant liver dysfunction; doses above the recommended range (up to 300 mg per day in studies) caused hepatocellular injury in a substantial proportion of patients, and single doses above 50 mg carry a higher risk. Oral bioavailability is estimated at 5 to 40%, with half-lives of 4 hours for naltrexone and 13 hours for 6-beta-naltrexol.

Participants / model
Adults with alcohol dependence or opioid dependence; label PK participants
Treatment
Naltrexone hydrochloride film-coated oral tablets, 50 mg
Follow-up
Label version effective 4 September 2026
Study design
FDA prescribing information
Funding
not stated in the source

The PK and safety statements describe 50 mg and higher doses, not LDN.

Read the original source
Danish trial: 99 women, 12 weeks, no significant pain difference

Randomized controlled trial

Due Bruun K et al. Lancet Rheumatol. 2024;6(1):e31-e39. PMID 38258677.

Pain intensity (0 to 10) changed -1.3 (95% CI -1.7 to -0.8) with naltrexone and -0.9 (-1.4 to -0.5) with placebo; between-group difference -0.34 (-0.95 to 0.27; p=0.27). Adverse events occurred in 41 of 49 (84%) versus 43 of 50 (86%), and 4 (8%) versus 3 (6%) stopped for adverse events. Not shown superior to placebo for pain.

Participants / model
99 women with fibromyalgia
Treatment
Oral naltrexone 6 mg a day (n=49) or placebo (n=50)
Follow-up
12 weeks
Study design
Single-centre randomized trial (NCT04270877)
Funding
not stated in the source

The authors suggested testing an effect on memory problems.

Read the original source
INNOVA: 98 women, 12 months, no meaningful benefit

Randomized controlled trial

Rodríguez-Freire C et al. Eur J Pain. 2026;30(6):e70321. PMID 42385209.

At 3 months, pain intensity changed -0.33 points with naltrexone and -0.64 with placebo, an adjusted between-group difference of 0.49 (p = 0.236, d = 0.19). Secondary outcomes at 3, 6 and 12 months showed minor and inconsistent changes. Adverse events were reported by 33 (68.8%) on naltrexone and 36 (72%) on placebo, with no treatment-related serious events.

Participants / model
98 women with fibromyalgia
Treatment
Oral naltrexone 4.5 mg a day (n=48) or placebo (n=50)
Follow-up
12 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The authors concluded LDN was well tolerated but gave no clinically meaningful benefit over placebo.

Read the original source
Crossover trial: 31 women, pain down 28.8% versus 18.0%

Randomized controlled trial

Younger J et al. Arthritis Rheum. 2013;65(2):529-38. PMID 23359310.

Pain fell 28.8% from baseline on naltrexone versus 18.0% on placebo (P = 0.016). Satisfaction with life (P = 0.045) and mood (P = 0.039) improved; fatigue and sleep did not. Response occurred in 32% versus 11% (P = 0.05). Tolerability matched placebo and no serious side effects were reported.

Participants / model
31 women with fibromyalgia
Treatment
Oral naltrexone 4.5 mg a day or placebo
Follow-up
not stated in the source
Study design
Randomized, double-blind, counterbalanced crossover trial
Funding
not stated in the source

The title calls the trial small, and the authors call for parallel-group trials.

Read the original source
2024 meta-analysis: 4 trials, 222 patients; corrigendum and disputing letter

Systematic review and meta-analysis

Vatvani AD et al. Korean J Pain. 2024;37(4):367-378. PMID 39344363.

Lower pain scores with LDN than placebo (mean difference -0.86, 95% CI -1.20 to -0.51) and a higher pressure pain threshold; no difference on the revised Fibromyalgia Impact Questionnaire; more vivid dreams and nausea; no difference in serious adverse events. A later letter by authors of the Danish trial reported inflated responder counts, pooling of different pain scales as raw mean differences and inconsistent handling of crossover data, and their re-analysis found no significant difference (standardized mean difference -0.25, 95% CI -0.59 to 0.09, in the 12-week studies).

Participants / model
Patients with fibromyalgia in 4 pooled randomized trials (222 patients)
Treatment
Oral LDN versus placebo
Follow-up
Pooled trials
Study design
Meta-analysis of randomized trials, with a published corrigendum and a disputing letter
Funding
not stated in the source

The corrigendum's content is not described here. The letter's authors disclose having published an LDN trial. The meta-analysis predates the INNOVA trial.

Read the original source
Cochrane review: 2 trials, 46 participants, low-quality evidence

Systematic review and meta-analysis

Parker CE et al. Cochrane Database Syst Rev. 2018;4(4):CD010410. PMID 29607497.

In adults, clinical remission was 30% (5 of 18) versus 18% (3 of 16) on placebo (RR 1.48, 95% CI 0.42 to 5.24, not significant); 70-point clinical response 83% (15 of 18) versus 38% (6 of 16) (RR 2.22, 1.14 to 4.32); endoscopic response 72% (13 of 18) versus 25% (4 of 16) (RR 2.89, 1.18 to 7.08). Adverse events did not differ and no serious adverse events were reported. Evidence rated low quality because of serious imprecision and insufficient for firm conclusions.

Participants / model
34 adults and 12 children with active Crohn's disease
Treatment
Oral LDN 4.5 mg a day (adults); 0.1 mg/kg a day up to 4.5 mg (children)
Follow-up
12 weeks (adults) and 8 weeks (children)
Study design
Cochrane systematic review of 2 randomized trials
Funding
not stated in the source

Two small trials; the review rated the evidence low quality.

Read the original source

Why does low-dose naltrexone sit in A tier?

A reflects naltrexone as an old, well-characterized FDA-approved drug used off label, not an endorsement of LDN. The LDN-specific trials are mostly null, and the low-dose claims on their own would grade lower.

Approved drugs promoted for uses outside their labels are graded A on this site, and the grade rests on the approved molecule and its label. For the low-dose claims, the positive evidence is one 31-woman crossover trial and two small Crohn's trials rated low quality, against null results in fibromyalgia trials of 99 and 98 women, a multiple sclerosis trial of 96 people and a depression trial of 37 adults.

Naltrexone tablet label, version effective 4 September 2026: indication, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Naltrexone hydrochloride film-coated oral tablets, 50 mg (SpecGx), prescribing information, label version effective 4 September 2026. Set ID 06ff2d5a-e62b-4fa4-bbdb-01938535bc65.

The label covers alcohol dependence and blockade of the effects of exogenously administered opioids, with no indication for pain, fibromyalgia, autoimmune disease or mood. It contraindicates naltrexone in patients receiving opioid analgesics and in those currently dependent on opioids, and warns it can precipitate withdrawal. It reports hepatitis and clinically significant liver dysfunction; doses above the recommended range (up to 300 mg per day in studies) caused hepatocellular injury in a substantial proportion of patients, and single doses above 50 mg carry a higher risk. Oral bioavailability is estimated at 5 to 40%, with half-lives of 4 hours for naltrexone and 13 hours for 6-beta-naltrexol.

Participants / model
Adults with alcohol dependence or opioid dependence; label PK participants
Treatment
Naltrexone hydrochloride film-coated oral tablets, 50 mg
Follow-up
Label version effective 4 September 2026
Study design
FDA prescribing information
Funding
not stated in the source

The PK and safety statements describe 50 mg and higher doses, not LDN.

Read the original source
Drugs@FDA: naltrexone approvals, 1984 to 2014

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 018932 (REVIA), with related applications ANDA 074918, ANDA 076264, NDA 021897 (VIVITROL) and NDA 200063 (CONTRAVE). Dates read from the openFDA Drugs@FDA records on 11 October 2026.

FDA first approved oral naltrexone as REVIA under NDA 018932 on 20 November 1984 (marked discontinued). Generic tablets followed from 1998 (ANDA 074918, 8 May 1998). VIVITROL (NDA 021897) was approved on 13 April 2006 and CONTRAVE (NDA 200063) on 10 September 2014. Single-ingredient tablets are 50 mg, with 25 mg and 100 mg strengths for one generic (ANDA 076264); no application lists a single-ingredient product below 25 mg, and none covers fibromyalgia, autoimmune disease or mood.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1984 to 2014
Study design
FDA application records
Funding
not stated in the source

These records give approval dates and strengths. Indications come from the tablet label.

Read the original source
Crossover trial: 31 women, pain down 28.8% versus 18.0%

Randomized controlled trial

Younger J et al. Arthritis Rheum. 2013;65(2):529-38. PMID 23359310.

Pain fell 28.8% from baseline on naltrexone versus 18.0% on placebo (P = 0.016). Satisfaction with life (P = 0.045) and mood (P = 0.039) improved; fatigue and sleep did not. Response occurred in 32% versus 11% (P = 0.05). Tolerability matched placebo and no serious side effects were reported.

Participants / model
31 women with fibromyalgia
Treatment
Oral naltrexone 4.5 mg a day or placebo
Follow-up
not stated in the source
Study design
Randomized, double-blind, counterbalanced crossover trial
Funding
not stated in the source

The title calls the trial small, and the authors call for parallel-group trials.

Read the original source
Danish trial: 99 women, 12 weeks, no significant pain difference

Randomized controlled trial

Due Bruun K et al. Lancet Rheumatol. 2024;6(1):e31-e39. PMID 38258677.

Pain intensity (0 to 10) changed -1.3 (95% CI -1.7 to -0.8) with naltrexone and -0.9 (-1.4 to -0.5) with placebo; between-group difference -0.34 (-0.95 to 0.27; p=0.27). Adverse events occurred in 41 of 49 (84%) versus 43 of 50 (86%), and 4 (8%) versus 3 (6%) stopped for adverse events. Not shown superior to placebo for pain.

Participants / model
99 women with fibromyalgia
Treatment
Oral naltrexone 6 mg a day (n=49) or placebo (n=50)
Follow-up
12 weeks
Study design
Single-centre randomized trial (NCT04270877)
Funding
not stated in the source

The authors suggested testing an effect on memory problems.

Read the original source
INNOVA: 98 women, 12 months, no meaningful benefit

Randomized controlled trial

Rodríguez-Freire C et al. Eur J Pain. 2026;30(6):e70321. PMID 42385209.

At 3 months, pain intensity changed -0.33 points with naltrexone and -0.64 with placebo, an adjusted between-group difference of 0.49 (p = 0.236, d = 0.19). Secondary outcomes at 3, 6 and 12 months showed minor and inconsistent changes. Adverse events were reported by 33 (68.8%) on naltrexone and 36 (72%) on placebo, with no treatment-related serious events.

Participants / model
98 women with fibromyalgia
Treatment
Oral naltrexone 4.5 mg a day (n=48) or placebo (n=50)
Follow-up
12 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The authors concluded LDN was well tolerated but gave no clinically meaningful benefit over placebo.

Read the original source
Cochrane review: 2 trials, 46 participants, low-quality evidence

Systematic review and meta-analysis

Parker CE et al. Cochrane Database Syst Rev. 2018;4(4):CD010410. PMID 29607497.

In adults, clinical remission was 30% (5 of 18) versus 18% (3 of 16) on placebo (RR 1.48, 95% CI 0.42 to 5.24, not significant); 70-point clinical response 83% (15 of 18) versus 38% (6 of 16) (RR 2.22, 1.14 to 4.32); endoscopic response 72% (13 of 18) versus 25% (4 of 16) (RR 2.89, 1.18 to 7.08). Adverse events did not differ and no serious adverse events were reported. Evidence rated low quality because of serious imprecision and insufficient for firm conclusions.

Participants / model
34 adults and 12 children with active Crohn's disease
Treatment
Oral LDN 4.5 mg a day (adults); 0.1 mg/kg a day up to 4.5 mg (children)
Follow-up
12 weeks (adults) and 8 weeks (children)
Study design
Cochrane systematic review of 2 randomized trials
Funding
not stated in the source

Two small trials; the review rated the evidence low quality.

Read the original source
MS trial: 96 people, 17 weeks, no meaningful difference

Randomized controlled trial

Sharafaddinzadeh N et al. Mult Scler. 2010;16(8):964-9. PMID 20534644.

No meaningful difference between LDN and placebo on pain, energy, emotional well-being, social, cognitive or sexual function, role limitations, health distress or overall quality of life (MSQoL-54). Health perception scores differed between groups at baseline, mid-study and the end. The authors called LDN relatively safe but its efficacy under question.

Participants / model
96 people aged 15 to 65 with relapsing-remitting or secondary progressive multiple sclerosis
Treatment
Oral LDN or placebo; dose not stated in the abstract
Follow-up
17 weeks
Study design
Randomized, double-blind, placebo-controlled trial (crossover design per the abstract)
Funding
not stated in the source

Quality-of-life outcomes only.

Read the original source
Depression trial: 37 adults, 12 weeks, no difference (p = 0.97)

Randomized controlled trial

Moloney BD et al. Front Pharmacol. 2026;17:1767654. PMID 41868116.

MADRS scores fell 10.5 (SD 5.6) with LDN and 9.8 (SD 5.9) with placebo, with no difference between groups (p = 0.97). LDN did not change high-sensitivity C-reactive protein or exploratory measures of depression, behavioral activation, quality of life, sickness symptoms or mood.

Participants / model
37 adults with major depressive disorder and moderate symptoms taking antidepressants
Treatment
Oral LDN up to 4.5 mg a day or placebo, added to antidepressants
Follow-up
12 weeks
Study design
Randomized placebo-controlled trial (ACTRN12622000881730)
Funding
not stated in the source

The one randomized mood trial reviewed for this page.

Read the original source

Studies and sources

PubChem: naltrexone and naltrexone hydrochloride identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 5360515 (naltrexone) and CID 5485201 (naltrexone hydrochloride).

Naltrexone free base: C20H23NO4, 341.4 g/mol, CAS 16590-41-3. Naltrexone hydrochloride, the salt in the approved tablets: C20H24ClNO4, 377.9 g/mol, CAS 16676-29-2. LDN is not a separate molecule.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule and salt
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Trial abstracts do not say whether doses are expressed as the salt or the free base.

Read the original source
Naltrexone tablet label, version effective 4 September 2026: indication, warnings, PK

FDA prescribing information

DailyMed, U.S. National Library of Medicine. Naltrexone hydrochloride film-coated oral tablets, 50 mg (SpecGx), prescribing information, label version effective 4 September 2026. Set ID 06ff2d5a-e62b-4fa4-bbdb-01938535bc65.

The label covers alcohol dependence and blockade of the effects of exogenously administered opioids, with no indication for pain, fibromyalgia, autoimmune disease or mood. It contraindicates naltrexone in patients receiving opioid analgesics and in those currently dependent on opioids, and warns it can precipitate withdrawal. It reports hepatitis and clinically significant liver dysfunction; doses above the recommended range (up to 300 mg per day in studies) caused hepatocellular injury in a substantial proportion of patients, and single doses above 50 mg carry a higher risk. Oral bioavailability is estimated at 5 to 40%, with half-lives of 4 hours for naltrexone and 13 hours for 6-beta-naltrexol.

Participants / model
Adults with alcohol dependence or opioid dependence; label PK participants
Treatment
Naltrexone hydrochloride film-coated oral tablets, 50 mg
Follow-up
Label version effective 4 September 2026
Study design
FDA prescribing information
Funding
not stated in the source

The PK and safety statements describe 50 mg and higher doses, not LDN.

Read the original source
Drugs@FDA: naltrexone approvals, 1984 to 2014

Regulatory record

U.S. Food and Drug Administration. Drugs@FDA application record for NDA 018932 (REVIA), with related applications ANDA 074918, ANDA 076264, NDA 021897 (VIVITROL) and NDA 200063 (CONTRAVE). Dates read from the openFDA Drugs@FDA records on 11 October 2026.

FDA first approved oral naltrexone as REVIA under NDA 018932 on 20 November 1984 (marked discontinued). Generic tablets followed from 1998 (ANDA 074918, 8 May 1998). VIVITROL (NDA 021897) was approved on 13 April 2006 and CONTRAVE (NDA 200063) on 10 September 2014. Single-ingredient tablets are 50 mg, with 25 mg and 100 mg strengths for one generic (ANDA 076264); no application lists a single-ingredient product below 25 mg, and none covers fibromyalgia, autoimmune disease or mood.

Participants / model
Not a clinical population
Treatment
Drug applications
Follow-up
Approvals from 1984 to 2014
Study design
FDA application records
Funding
not stated in the source

These records give approval dates and strengths. Indications come from the tablet label.

Read the original source
Crossover trial: 31 women, pain down 28.8% versus 18.0%

Randomized controlled trial

Younger J et al. Arthritis Rheum. 2013;65(2):529-38. PMID 23359310.

Pain fell 28.8% from baseline on naltrexone versus 18.0% on placebo (P = 0.016). Satisfaction with life (P = 0.045) and mood (P = 0.039) improved; fatigue and sleep did not. Response occurred in 32% versus 11% (P = 0.05). Tolerability matched placebo and no serious side effects were reported.

Participants / model
31 women with fibromyalgia
Treatment
Oral naltrexone 4.5 mg a day or placebo
Follow-up
not stated in the source
Study design
Randomized, double-blind, counterbalanced crossover trial
Funding
not stated in the source

The title calls the trial small, and the authors call for parallel-group trials.

Read the original source
Danish trial: 99 women, 12 weeks, no significant pain difference

Randomized controlled trial

Due Bruun K et al. Lancet Rheumatol. 2024;6(1):e31-e39. PMID 38258677.

Pain intensity (0 to 10) changed -1.3 (95% CI -1.7 to -0.8) with naltrexone and -0.9 (-1.4 to -0.5) with placebo; between-group difference -0.34 (-0.95 to 0.27; p=0.27). Adverse events occurred in 41 of 49 (84%) versus 43 of 50 (86%), and 4 (8%) versus 3 (6%) stopped for adverse events. Not shown superior to placebo for pain.

Participants / model
99 women with fibromyalgia
Treatment
Oral naltrexone 6 mg a day (n=49) or placebo (n=50)
Follow-up
12 weeks
Study design
Single-centre randomized trial (NCT04270877)
Funding
not stated in the source

The authors suggested testing an effect on memory problems.

Read the original source
INNOVA: 98 women, 12 months, no meaningful benefit

Randomized controlled trial

Rodríguez-Freire C et al. Eur J Pain. 2026;30(6):e70321. PMID 42385209.

At 3 months, pain intensity changed -0.33 points with naltrexone and -0.64 with placebo, an adjusted between-group difference of 0.49 (p = 0.236, d = 0.19). Secondary outcomes at 3, 6 and 12 months showed minor and inconsistent changes. Adverse events were reported by 33 (68.8%) on naltrexone and 36 (72%) on placebo, with no treatment-related serious events.

Participants / model
98 women with fibromyalgia
Treatment
Oral naltrexone 4.5 mg a day (n=48) or placebo (n=50)
Follow-up
12 months
Study design
Randomized placebo-controlled trial
Funding
not stated in the source

The authors concluded LDN was well tolerated but gave no clinically meaningful benefit over placebo.

Read the original source
2024 meta-analysis: 4 trials, 222 patients; corrigendum and disputing letter

Systematic review and meta-analysis

Vatvani AD et al. Korean J Pain. 2024;37(4):367-378. PMID 39344363.

Lower pain scores with LDN than placebo (mean difference -0.86, 95% CI -1.20 to -0.51) and a higher pressure pain threshold; no difference on the revised Fibromyalgia Impact Questionnaire; more vivid dreams and nausea; no difference in serious adverse events. A later letter by authors of the Danish trial reported inflated responder counts, pooling of different pain scales as raw mean differences and inconsistent handling of crossover data, and their re-analysis found no significant difference (standardized mean difference -0.25, 95% CI -0.59 to 0.09, in the 12-week studies).

Participants / model
Patients with fibromyalgia in 4 pooled randomized trials (222 patients)
Treatment
Oral LDN versus placebo
Follow-up
Pooled trials
Study design
Meta-analysis of randomized trials, with a published corrigendum and a disputing letter
Funding
not stated in the source

The corrigendum's content is not described here. The letter's authors disclose having published an LDN trial. The meta-analysis predates the INNOVA trial.

Read the original source
Cochrane review: 2 trials, 46 participants, low-quality evidence

Systematic review and meta-analysis

Parker CE et al. Cochrane Database Syst Rev. 2018;4(4):CD010410. PMID 29607497.

In adults, clinical remission was 30% (5 of 18) versus 18% (3 of 16) on placebo (RR 1.48, 95% CI 0.42 to 5.24, not significant); 70-point clinical response 83% (15 of 18) versus 38% (6 of 16) (RR 2.22, 1.14 to 4.32); endoscopic response 72% (13 of 18) versus 25% (4 of 16) (RR 2.89, 1.18 to 7.08). Adverse events did not differ and no serious adverse events were reported. Evidence rated low quality because of serious imprecision and insufficient for firm conclusions.

Participants / model
34 adults and 12 children with active Crohn's disease
Treatment
Oral LDN 4.5 mg a day (adults); 0.1 mg/kg a day up to 4.5 mg (children)
Follow-up
12 weeks (adults) and 8 weeks (children)
Study design
Cochrane systematic review of 2 randomized trials
Funding
not stated in the source

Two small trials; the review rated the evidence low quality.

Read the original source
MS trial: 96 people, 17 weeks, no meaningful difference

Randomized controlled trial

Sharafaddinzadeh N et al. Mult Scler. 2010;16(8):964-9. PMID 20534644.

No meaningful difference between LDN and placebo on pain, energy, emotional well-being, social, cognitive or sexual function, role limitations, health distress or overall quality of life (MSQoL-54). Health perception scores differed between groups at baseline, mid-study and the end. The authors called LDN relatively safe but its efficacy under question.

Participants / model
96 people aged 15 to 65 with relapsing-remitting or secondary progressive multiple sclerosis
Treatment
Oral LDN or placebo; dose not stated in the abstract
Follow-up
17 weeks
Study design
Randomized, double-blind, placebo-controlled trial (crossover design per the abstract)
Funding
not stated in the source

Quality-of-life outcomes only.

Read the original source
Depression trial: 37 adults, 12 weeks, no difference (p = 0.97)

Randomized controlled trial

Moloney BD et al. Front Pharmacol. 2026;17:1767654. PMID 41868116.

MADRS scores fell 10.5 (SD 5.6) with LDN and 9.8 (SD 5.9) with placebo, with no difference between groups (p = 0.97). LDN did not change high-sensitivity C-reactive protein or exploratory measures of depression, behavioral activation, quality of life, sickness symptoms or mood.

Participants / model
37 adults with major depressive disorder and moderate symptoms taking antidepressants
Treatment
Oral LDN up to 4.5 mg a day or placebo, added to antidepressants
Follow-up
12 weeks
Study design
Randomized placebo-controlled trial (ACTRN12622000881730)
Funding
not stated in the source

The one randomized mood trial reviewed for this page.

Read the original source

Why is Low-dose naltrexone in A tier?

A reflects an old, well-characterized FDA-approved drug used outside its label, which is how approved drugs used off label are graded here. It does not endorse the low-dose claims, which on their own would sit lower: the larger and longer fibromyalgia trials were null, the Crohn's disease evidence covers 46 people and is rated low quality, and the depression and multiple sclerosis trials found no difference from placebo.