Compare notes on r/BodyHackGuideCompare notes with other researchers. Join r/BodyHackGuide

Low-Dose Naltrexone (LDN)

Status: Approved (prescription)
Evidence: Not graded on a research bench yet

Low-dose naltrexone (LDN) is naltrexone, an opioid receptor antagonist approved by the FDA for alcohol and opioid dependence, prescribed off-label at a few milligrams a day, a dose not approved for any condition (US prescribing information for naltrexone tablets and for extended-release injectable naltrexone; PMID: 42060160).

Reviewed 27 October 2026

01Overview

What Low-Dose Naltrexone (LDN) is

Most of the evidence on low-dose naltrexone consists of case reports and small studies, and a 2026 review of 105 studies, 15 of them randomized, found that early positive results from uncontrolled studies were rarely replicated in placebo-controlled trials (PMID: 42060160). In fibromyalgia, a 31-woman crossover trial at Stanford reported less daily pain on low-dose naltrexone than on placebo, but the two largest placebo-controlled trials, in 99 women in Denmark and 98 women in Spain, found no significant difference in pain (PMID: 23359310, PMID: 38258677, PMID: 42385209). Naltrexone blocks opioid drugs and can bring on withdrawal in people who use or depend on opioids, and its label lists people taking opioid pain medicines or dependent on opioids among its contraindications (US prescribing information for naltrexone tablets).

How it works

What low dose means

Naltrexone blocks opioid receptors without activating them (a pure opioid antagonist) and does so by competing with opioids for the same receptors (competitive antagonism) (US prescribing information for naltrexone tablets). Reviews define low-dose naltrexone as about 1 to 5 mg a day (PMID: 30248938, PMID: 40962192), and a 2026 review found that most low-dose studies gave 4.5 mg a day (PMID: 42060160). A 2018 review separates this range from very low doses (1 microgram to 1 mg a day), used mainly to make methadone tapers easier to tolerate, and ultra-low doses (under 1 microgram a day), used mainly to lower opioid needs after surgery (PMID: 30248938). The smallest single-ingredient naltrexone tablet approved in the US is 25 mg (Drugs@FDA), and low-dose naltrexone is commonly prepared by compounding pharmacies (PMID: 40962192). Bernard Bihari described low-dose naltrexone as an immune stabilizing agent in HIV/AIDS in a 1995 letter (PMID: 11361353).

Read the full mechanismShow less

Proposed mechanism 1: brief blockade and an opioid rebound (hypothesis)

One proposed mechanism is that a low dose blocks opioid receptors only briefly, and that the body responds by raising its own opioid signaling, with more of its own opioids (endogenous opioids such as enkephalins and endorphins) and more opioid receptors (PMID: 30248938, PMID: 40962192). This is a hypothesis built mostly on cell and animal work. Much of that work comes from Ian Zagon and Patricia McLaughlin at Penn State, whose 2015 review argued that the duration of opioid receptor blockade, not the dose itself, decides the biological response: intermittent blockade with low doses depressed cell replication, while continuous blockade with high doses enhanced growth (PMID: 26119823). Their model centers on an enkephalin they call opioid growth factor ([Met5]-enkephalin) and its receptor (the OGF-OGFr axis) (PMID: 26119823, PMID: 21807817).

Cell data: in human cancer cell lines, naltrexone raised levels of opioid growth factor and its receptor at the protein level, and brief exposure slowed cell growth (PMID: 21807817). Animal data: in mice with experimental autoimmune encephalomyelitis, a model of multiple sclerosis, daily naltrexone at 0.1 mg/kg reduced disease severity while 10 mg/kg did not, and the authors attributed the effect to endogenous opioids acting in the rebound period after each dose (PMID: 19855075). Human data are indirect: in an uncontrolled 6-month pilot in 40 people with primary progressive multiple sclerosis, blood beta-endorphin rose during treatment (PMID: 18728058).

Proposed mechanism 2: TLR4 and microglia (hypothesis)

A second, separate hypothesis is that low-dose naltrexone reduces inflammation in the nervous system by acting on the resident immune cells of the brain and spinal cord (microglia) through a receptor that senses bacterial products (toll-like receptor 4, TLR4), apart from any action on opioid receptors (PMID: 24526250, PMID: 30248938). Jarred Younger, who ran the Stanford fibromyalgia trials, reviewed this model in 2014; the review proposed that these effects may be specific to low doses and independent of opioid receptors, and called the use of low-dose naltrexone for chronic disorders highly experimental (PMID: 24526250).

The naltrexone in tablets is the (-) form (PubChem CID 5360515 lists it as (-)-naltrexone), and its mirror-image form, (+)-naltrexone, does not act on opioid receptors (PMID: 26603732). Cell and animal data: Linda Watkins's group at the University of Colorado reported that (+)-naltrexone and both mirror-image forms of naloxone blocked TLR4 in engineered and microglial cell lines and reversed nerve-injury pain in rats on chronic infusion (PMID: 18662331). A 2013 study in TLR4 reporter cells found that opioid agonists and antagonists, naloxone among them, all reduced signaling from bacterial lipopolysaccharide; the two agents tested further did so non-competitively rather than by competing with lipopolysaccharide, which the authors attributed to a separate opioid site in the TLR4 pathway that needs confirmation (PMID: 23083095).

Human data: in 8 women with fibromyalgia, 8 weeks of low-dose naltrexone in a single-blind study was followed by lower blood levels of many signaling proteins of the immune system (cytokines), among them IL-1beta, IL-6 and TNF-alpha (PMID: 28536359). In the Danish FINAL trial, conditioned pain modulation was the only one of five exploratory measures, three of pain processing and two of muscle fatigue, that differed from placebo, and the authors judged that difference a random finding (PMID: 40214857).

Chemistry and pharmacokinetics

Naltrexone (PubChem CID 5360515) has the formula C20H23NO4 and a molecular weight of 341.4 g/mol; tablets contain the salt naltrexone hydrochloride (PubChem CID 5485201, C20H24ClNO4, 377.9 g/mol, CAS 16676-29-2). The naltrexone tablet label gives an oral bioavailability of 5 to 40 percent, because much of each dose is broken down before it reaches the circulation (first-pass metabolism), and peak blood levels within one hour (US prescribing information for naltrexone tablets). The label's mean elimination half-lives are 4 hours for naltrexone and 13 hours for its main metabolite, 6-beta-naltrexol, which is believed to share in its activity (US prescribing information for naltrexone tablets). A 2023 Danish fibromyalgia trial measured blood levels after 4.5 mg and found fast absorption, with 6-beta-naltrexol levels more than 10 times those of naltrexone; the trial did not calculate a half-life (PMID: 38226027).

Studied for

Fibromyalgia
Crohn's disease
Multiple sclerosis
Chronic pain
Long COVID
Neuroinflammation
Opioid pharmacology
Painful diabetic neuropathy

Benefits listed

Daily pain in a 31-woman fibromyalgia crossover trial at Stanford (PMID: 23359310)
Crohn's disease activity (70-point CDAI response) and endoscopic response in a 34-patient trial (PMID: 21380937)
Fatigue scores in a Dutch Crohn's disease trial that found no clinical or endoscopic benefit (PMID: 42701992)
Mental health quality-of-life scores in a multiple sclerosis crossover trial that enrolled 80 people (PMID: 20695007)

Show 3 moreShow less

Spasticity in an uncontrolled 40-person pilot in primary progressive multiple sclerosis (PMID: 18728058)
Fatigue, sleep and pain in uncontrolled long COVID studies (PMID: 42463201)
Pain in painful diabetic neuropathy compared with amitriptyline, without a placebo group (PMID: 34014028)

02Research

Free with email

What the research shows

No research bench grades Low-Dose Naltrexone (LDN) yet. Benches compare compounds people pair, with the evidence for each.

Key research findings

Overview

A 2026 narrative review identified 105 human studies of naltrexone at doses of 12.5 mg or less, including 15 randomized controlled trials across chronic pain, autoimmune and neuroimmune disorders, gastrointestinal disease, skin conditions, post-infectious syndromes, mental health and cancer (PMID: 42060160). In that review, early positive findings from uncontrolled studies were rarely replicated in placebo-controlled trials, and the authors concluded that the evidence does not support routine clinical use (PMID: 42060160). The early fibromyalgia trials came from Jarred Younger's laboratory at Stanford, and the early Crohn's disease trials and the opioid growth factor work from Penn State (Jill Smith, Ian Zagon and Patricia McLaughlin) (PMID: 19453963, PMID: 23359310, PMID: 17222320, PMID: 21380937, PMID: 26119823).

Read all the findingsShow less

Fibromyalgia

FINAL trial, Denmark, published 2024. A single-center, double-blind trial randomized 99 women aged 18 to 64 to low-dose naltrexone 6 mg a day or placebo for 12 weeks. The primary endpoint, change in pain on a 0 to 10 scale, was not met: pain fell by 1.3 points with low-dose naltrexone and 0.9 points with placebo, a between-group difference of -0.34 points (95% CI -0.95 to 0.27, p=0.27). Adverse events affected 84 and 86 percent, and the authors suggested that low-dose naltrexone might help memory problems and called for trials to test this (PMID: 38258677). The share with at least 30 percent less pain was 20 of 49 against 13 of 50, a difference that was not significant (risk ratio 1.57, 95% CI 0.88 to 2.79) (PMID: 41469218). A 2026 exploratory analysis of the same trial found no significant difference in the share of women with a 30 percent improvement in memory problems or five other symptoms (PMID: 42586891).
INNOVA trial, Spain, published 2026. A single-center, double-blind trial randomized 98 women to low-dose naltrexone 4.5 mg a day (48) or placebo (50), added to their usual treatment, with follow-up to 12 months. The primary endpoint, change in pain on a 0 to 10 scale at 3 months, was not met: pain fell 0.33 points with low-dose naltrexone and 0.64 points with placebo (adjusted difference 0.49, p=0.236). Secondary outcomes changed little and inconsistently, and the authors found no clinically meaningful benefit over placebo at short- or long-term follow-up (PMID: 42385209). The protocol described INNOVA as a phase III trial (PMID: 34992118).
Bested and colleagues, Denmark, 2023. A double-blind, placebo-controlled crossover trial randomized 58 patients with fibromyalgia to low-dose naltrexone 4.5 mg a day and placebo in treatment periods of about three weeks. Neither primary endpoint differed, the revised Fibromyalgia Impact Questionnaire (p=0.3) and summed pain intensity ratings (p=0.4), and the authors found no clinically relevant pain relief (PMID: 38226027).
Younger and colleagues, Stanford, 2013. A randomized, double-blind, placebo-controlled, counterbalanced crossover trial in 31 women gave low-dose naltrexone 4.5 mg a day. Daily self-reported pain fell 28.8 percent from baseline on low-dose naltrexone against 18.0 percent on placebo (p=0.016). Satisfaction with life and mood improved while fatigue and sleep did not, and 32 percent met the response criteria on low-dose naltrexone against 11 percent on placebo (p=0.05) (PMID: 23359310).
Younger and Mackey, Stanford, 2009. In a single-blind pilot, 10 women had 2 weeks of baseline, 2 weeks of placebo, 8 weeks of low-dose naltrexone 4.5 mg and 2 weeks of washout. Symptoms fell by more than 30 percent compared with placebo, mechanical and heat pain thresholds improved, and baseline erythrocyte sedimentation rate predicted more than 80 percent of the variance in response, with the largest gains in women with higher rates (PMID: 19453963).
Brazil, factorial trial. Eighty-six women with fibromyalgia were randomized to low-dose naltrexone or placebo for 26 days, with active or sham transcranial direct current stimulation in the last five sessions. Pain fell within both low-dose naltrexone groups and also in the placebo group with sham stimulation, and the authors noted a placebo effect (PMID: 35988815).
Pooled analyses. Meta-analyses published before the INNOVA results disagreed. One pooled five randomized trials and found lower pain with low-dose naltrexone (standardized mean difference -0.61, 95% CI -1.14 to -0.08) (PMID: 40337423), and another, which included eight clinical trials, found no significant difference in pain between low-dose naltrexone and placebo (standardized mean difference -0.50, 95% CI -1.19 to 0.19) (PMID: 40272382). The FINAL investigators reanalyzed pain scores from four randomized trials and found no significant effect after 3 or 12 weeks (12-week standardized mean difference -0.25, 95% CI -0.59 to 0.09); re-pooling the two trials that reported a 30 percent pain response gave more responders on low-dose naltrexone (odds ratio 2.47, 95% CI 1.10 to 5.54) (PMID: 41469218).

Crohn's disease and inflammatory bowel disease

Smith and colleagues, Penn State, 2011. Of 40 adults with active Crohn's disease enrolled, 34 were randomized to low-dose naltrexone 4.5 mg a day or placebo for 12 weeks, double-blind. The primary endpoint was met: 88 percent on low-dose naltrexone had at least a 70-point fall in the Crohn's Disease Activity Index against 40 percent on placebo (p=0.009). Endoscopic response was 78 percent against 28 percent (p=0.008), and 33 percent against 8 percent reached an endoscopy score under 6, a difference that was not statistically significant (PMID: 21380937). In the Cochrane review's intention-to-treat analysis, the 70-point response was 15 of 18 against 6 of 16 (risk ratio 2.22, 95% CI 1.14 to 4.32), while clinical remission at 12 weeks, 5 of 18 against 3 of 16, did not differ significantly (PMID: 29607497).
Smith and colleagues, Penn State, 2007. In an open-label pilot, 17 adults with active Crohn's disease took low-dose naltrexone 4.5 mg each evening for 12 weeks alongside their stable existing treatment. Disease activity scores fell (p=0.01), 89 percent responded and 67 percent reached remission, and sleep disturbance in 7 patients was the most common side effect (PMID: 17222320).
Smith and colleagues, Penn State, 2013, children. Fourteen children aged 8 to 17 with moderate to severe Crohn's disease were randomized to naltrexone 0.1 mg/kg or placebo for 8 weeks, followed by 8 weeks of open-label naltrexone. The study's aim was safety and tolerability: there were no serious adverse events, disease activity scores fell from 34.2 to 21.7 after 8 weeks of naltrexone (p=0.005), and 25 percent were in remission at the end of the study (PMID: 23188075).
Cochrane review, 2018. Two randomized trials with 46 participants met the criteria. The reviewers rated the evidence as low quality because of sparse data and found it insufficient for firm conclusions on efficacy or safety in active Crohn's disease (PMID: 29607497).
Erasmus MC Rotterdam, open-label, 2018. In 47 people with inflammatory bowel disease not responding to standard therapy, adding low-dose naltrexone was followed by clinical improvement in 74.5 percent and remission in 25.5 percent over 12 weeks; in the same paper, naltrexone improved wound healing and reduced endoplasmic reticulum stress in intestinal cell cultures and organoids (PMID: 29523156).
Netherlands multicenter trial, published 2026. The Rotterdam group then ran a double-blind trial at 7 Dutch hospitals that randomized adults with mild to moderate active Crohn's disease to low-dose naltrexone 4.5 mg a day or placebo for 12 weeks. The trial stopped early for futility after 41 patients. The primary endpoint, endoscopic remission at week 12, was not met: 5.6 percent against 18.8 percent (p=0.233). Clinical remission was higher with placebo, 70.0 percent against 22.2 percent (p=0.037). Fatigue scores improved more with low-dose naltrexone (p=0.012), and no serious adverse events occurred (PMID: 42701992). The protocol had planned 61 patients per group (PMID: 35396307).

Multiple sclerosis

Cree and colleagues, UCSF, 2010. A single-center, double-masked, placebo-controlled crossover trial gave low-dose naltrexone 4.5 mg nightly for 8 weeks. Of 80 people enrolled, 60 completed, and dropouts and data errors reduced the trial's statistical power. Low-dose naltrexone improved the SF-36 Mental Component Summary by 3.3 points (p=0.04) and the Mental Health Inventory by 6 points (p<0.01). Pain Effects Scale scores improved by 1.6 points (p=0.04) and Perceived Deficits Questionnaire scores by 2.4 points (p=0.05). No serious adverse events occurred (PMID: 20695007). A 2026 review notes that fatigue and physical function did not improve in this trial (PMID: 42060160).
Sharafaddinzadeh and colleagues, Iran, 2010. A 17-week randomized, double-blind, placebo-controlled trial with a crossover design enrolled 96 adults with relapsing-remitting or secondary progressive multiple sclerosis. The primary outcome, physical and mental health scores on the MSQoL-54 questionnaire, did not differ meaningfully between groups, and the authors judged low-dose naltrexone relatively safe but its efficacy questionable (PMID: 20534644).
Gironi and colleagues, Italy, 2008. A 6-month open-label, multicenter phase II pilot in 40 people with primary progressive multiple sclerosis had safety and tolerability as its primary endpoints. There were 5 dropouts and 2 major adverse events, spasticity fell by the end of the trial and beta-endorphin levels rose, and the authors concluded that low-dose naltrexone was safe and well tolerated in this group (PMID: 18728058). A 2026 review notes that pain increased during treatment and that fatigue and depression did not change (PMID: 42060160).
Norway prescription data, 2017. Among 341 people with multiple sclerosis who started low-dose naltrexone in 2013, use of other multiple sclerosis medicines over the next two years did not change beyond national trends (PMID: 29099849).

Long COVID and post-COVID fatigue

No published randomized trials. A 2026 systematic review that searched to 5 May 2026 found no randomized controlled trials of low-dose naltrexone in long COVID. Four uncontrolled before-and-after studies from the USA and Ireland (155 patients, 1 to 6 mg a day) showed improvements in fatigue, brain fog, sleep, pain and daily functioning, with low certainty of evidence, and no serious adverse events were reported in the two studies that assessed safety (PMID: 42463201).
O'Kelly and colleagues, Dublin, 2022. Of 52 people with post-COVID syndrome enrolled, 38 started low-dose naltrexone (1 mg a day in month one, 2 mg in month two) and 36 completed the follow-up questionnaire. Scores improved in 6 of 7 measures, including energy, pain, concentration and sleep (p of 0.001 or less), with no control group (PMID: 35814187).
British Columbia trial. A double-blind, placebo-controlled trial (NCT05430152) published its design in 2024: 160 adults with post-COVID fatigue syndrome, 16 weeks, with fatigue severity as the primary outcome (PMID: 38740499). ClinicalTrials.gov lists the trial as completed on 28 February 2026 with 160 participants, and no results had been published in PubMed by 21 October 2026 (NCT05430152).

Other randomized trials

Painful diabetic neuropathy, India, 2021. In a double-blind crossover trial, 67 participants received naltrexone 2 mg a day, raised to 4 mg if pain fell by less than 20 percent, or amitriptyline 10 mg, raised to 25 or 50 mg, for 6 weeks each. The difference in pain change between the drugs was not significant (1.5 points on a visual analog scale, 95% CI -1.11 to 4.13, intention to treat), with 8 adverse events on naltrexone against 52 on amitriptyline (p<0.001), and there was no placebo group (PMID: 34014028).
Depression, University of Auckland, 2026. In a randomized, double-blind trial, 37 adults with at least moderate major depression who were taking antidepressants received added low-dose naltrexone, up to 4.5 mg a day, or placebo for 12 weeks. The primary outcome, the Montgomery-Asberg depression score, fell 10.5 and 9.8 points, with no difference between groups (p=0.97), and low-dose naltrexone did not change C-reactive protein or the exploratory mood and quality-of-life measures (PMID: 41868116). The trial ended before reaching its planned size because of slow recruitment (PMID: 41868116).
Depression, Massachusetts General Hospital, 2017. Twelve adults with major depression relapsing on dopamine-acting antidepressant regimens were randomized to add naltrexone 1 mg twice a day or placebo for 3 weeks. The primary outcome, the 17-item Hamilton depression score, did not differ significantly (p=0.3), while the Montgomery-Asberg depression score fell more with low-dose naltrexone (p=0.035) (PMID: 27736689).
Arthritis pain, VA Boston, 2023. In a double-blind, placebo-controlled crossover pilot, 23 people with osteoarthritis or inflammatory arthritis completed 8 weeks of low-dose naltrexone 4.5 mg and 8 weeks of placebo. Pain interference, the primary outcome, did not differ (change of -23 against -22 points, p=0.90) (PMID: 37045708).
HIV, chronic pain and heavy drinking, Russia, 2024. A 45-person pilot randomized participants to low-dose naltrexone 4.5 mg a day, gabapentin or placebo for 8 weeks, and neither drug reduced pain severity or interference more than placebo (PMID: 38408060).
High-grade glioma, Duke University, 2022. In 110 patients randomized to low-dose naltrexone 4.5 mg at night or placebo for 16 weeks from the start of chemoradiation, quality of life and fatigue did not differ between groups (PMID: 35001215).
Lichen planopilaris, Iran. In 34 patients given topical clobetasol with low-dose naltrexone 3 mg or placebo, disease activity scores did not differ between groups (p=0.813) (PMID: 32449418).

Safety and side effects

In low-dose trials

In the two largest placebo-controlled fibromyalgia trials, adverse events were about as common with low-dose naltrexone as with placebo. In the Danish FINAL trial, 84 percent on low-dose naltrexone and 86 percent on placebo had an adverse event, 8 percent against 6 percent stopped because of one, and the only serious adverse event occurred on placebo (PMID: 38258677). In the Spanish INNOVA trial, 68.8 percent on low-dose naltrexone and 72 percent on placebo had an adverse event, mostly mild and short-lived, and none of five serious adverse events (four on low-dose naltrexone, one on placebo) was judged treatment related (PMID: 42385209). In INNOVA, nervous system disorders made up 21.1 percent of adverse events on low-dose naltrexone and 8.5 percent on placebo (p=0.024) (PMID: 42385209). A 2025 meta-analysis that included seven randomized chronic pain trials found more adverse events with low-dose naltrexone than with placebo (incidence rate ratio 1.4, 95% CI 1.12 to 1.75) (PMID: 40540205).

Read all the safety notesShow less

Sleep and dreams. Sleep disturbance was the most common side effect in the 2007 Crohn's disease pilot, reported by 7 of 17 patients (PMID: 17222320). In the 2009 Stanford fibromyalgia pilot, insomnia and vivid dreams were rare, minor and transient (PMID: 19453963). In the 2011 Crohn's disease trial, insomnia was reported by 5 patients in each group and unusual dreams by 2 on naltrexone and 3 on placebo (PMID: 21380937). A 2025 meta-analysis of fibromyalgia trials found vivid dreams more often with low-dose naltrexone than with placebo (risk ratio 2.41, 95% CI 1.77 to 3.28) (PMID: 40337423). In the 2026 Auckland depression trial, nightmares or abnormal dreams that participants attributed to treatment were reported by 8 of 19 on low-dose naltrexone and 3 of 18 on placebo, and sleep problems by 7 and 5 (PMID: 41868116).

Headache, nausea, fatigue and diarrhea. In a 2023 Danish crossover trial, patient diaries recorded headache in 9 people during low-dose naltrexone and 9 during placebo, fatigue in 9 and 4, nausea in 8 and 5, and dizziness in 7 and 4, all classed as minor; two people dropped out with nausea and vomiting just after starting (PMID: 38226027). The 2025 fibromyalgia meta-analysis found no significant link between low-dose naltrexone and headache (PMID: 40337423). Mild diarrhea was the most common adverse event with naltrexone in a diabetic neuropathy trial (PMID: 34014028), and 2 of 38 people who started low-dose naltrexone in an Irish long COVID study stopped because of new diarrhea (PMID: 35814187). A 2018 Cochrane review of the Crohn's disease trials found no significant differences from placebo in withdrawals for adverse events or in sleep disturbance, unusual dreams, headache, decreased appetite, nausea or fatigue, and no serious adverse events (PMID: 29607497).

Serious adverse events across doses. A 2019 meta-analysis of 89 placebo-controlled trials of oral naltrexone at any dose (11,194 participants, with studies in opioid users excluded) found no increase in serious adverse events, risk ratio 0.84 (95% CI 0.66 to 1.06) (PMID: 30642329). The result was consistent across doses and conditions, and 26 of the trials, with 4,960 participants, reported serious adverse events by group (PMID: 30642329).

At standard doses

In an open-label safety study of about 570 people with alcoholism taking naltrexone tablets, new adverse reactions in 2 percent or more were nausea (10 percent), headache (7 percent), dizziness (4 percent), nervousness (4 percent), fatigue (4 percent), insomnia (3 percent), vomiting (3 percent), anxiety (2 percent) and somnolence (2 percent) (US prescribing information for naltrexone tablets). The label also reports depression, suicide, suicide attempts and suicidal thinking after marketing in people treated for opioid dependence, with no causal relationship shown (US prescribing information for naltrexone tablets).

Liver

The naltrexone tablet label warns that hepatitis and clinically significant liver dysfunction were seen during clinical development and after marketing, often alongside other possible causes such as alcoholic liver disease, hepatitis B or C, or other liver-toxic drugs (US prescribing information for naltrexone tablets). The label describes the liver injury as dose related: at 300 mg a day, 5 of 26 obese people (19 percent) and none of 24 on placebo developed raised transaminases after three to eight weeks (US prescribing information for naltrexone tablets). Naltrexone exposure (AUC) was about 5 and 10 times higher in compensated and decompensated cirrhosis (US prescribing information for naltrexone tablets).

The boxed warning for hepatotoxicity has been removed from oral and injectable naltrexone labeling (PMID: 26717532), and a hospital medicine review on alcohol use disorder stated that earlier hepatotoxicity concerns had been disproven and that recent studies showed naltrexone to be safe in people with cirrhosis (PMID: 39655573). Liver data at low doses are limited. The 2007 Crohn's disease pilot noted no laboratory abnormalities (PMID: 17222320). The 2011 Crohn's disease trial excluded people with abnormal liver enzymes and recorded transient transaminase rises in 2 patients on naltrexone that resolved within a month, one of them during a respiratory infection (PMID: 21380937). A Penn State chart review of 54 people with multiple sclerosis found no significant differences in standard blood test values over follow-up of up to 50 months after diagnosis (PMID: 28607740).

Opioids

Naltrexone can bring on opioid withdrawal in anyone who is not free of opioids; the label describes symptoms within five minutes of a dose, lasting up to 48 hours, and postmarketing cases severe enough for hospital or intensive care admission (US prescribing information for naltrexone tablets). The label also warns that people may be more sensitive to opioids, even at lower doses, after naltrexone is stopped, that fatal overdoses have been reported after treatment ended, and that trying to overcome the blockade with large opioid doses can cause life-threatening or fatal overdose; the label does not address low doses (US prescribing information for naltrexone tablets). A 2017 case report described the opposite problem: a man taking low-dose naltrexone for multiple sclerosis became unresponsive after a single 5 mg dose of oxycodone and needed naloxone and a night in intensive care, and the authors suggested that low-dose naltrexone may make people more sensitive to opioids (PMID: 28410920).

Pregnancy, breastfeeding and children

The naltrexone label states that there are no adequate and well-controlled studies in pregnant women, that naltrexone increased early fetal loss in rats and rabbits at doses well above human doses, that it is unknown whether naltrexone passes into human milk, and that safe use under 18 years of age has not been established (US prescribing information for naltrexone tablets). A pilot trial of low-dose naltrexone in 14 children with Crohn's disease reported no serious adverse events (PMID: 23188075).

On PubMed

The search "low-dose naltrexone"[Title/Abstract] OR "low dose naltrexone"[Title/Abstract] on PubMed.

Browse studies on PubMed

Unlock the research summary

Enter your email to keep reading. It is free, and it opens these sections on every compound page in this browser.

A summary of the key research
Safety and side effects
A link to the PubMed results

You also get the free peptide cheat sheet by email. Unsubscribe anytime.

Have an account? Sign in

03Safety

Low-Dose Naltrexone side effects and interactions

Side effects

Common

Vivid or unusual dreams
Sleep disturbance or insomnia
Headache
Nausea
Fatigue
Mild diarrhea
Dizziness

Serious events

Precipitated opioid withdrawal in people using or dependent on opioids
Opioid overdose risk after stopping naltrexone or when trying to overcome the blockade (labeled warning)
Blocked opioid pain relief; one case report of unresponsiveness after a small oxycodone dose
Dose-related liver injury (labeled warning for naltrexone)
Depression and suicidal thinking reported after marketing in opioid dependence, with no causal link shown

Who should not use it

Contraindications

Opioid use. The naltrexone label lists as contraindications people receiving opioid pain medicines, people currently dependent on opioids, including those maintained on methadone or buprenorphine, people in acute opioid withdrawal, anyone who has failed a naloxone challenge test or has a positive urine screen for opioids, and anyone with a history of sensitivity to naltrexone (US prescribing information for naltrexone tablets).

Read all the contraindications and cautionsShow less

Precipitated withdrawal. For people previously dependent on short-acting opioids, the label calls for an opioid-free interval of at least 7 to 10 days before naltrexone is started, and it says people coming off buprenorphine or methadone may be vulnerable to precipitated withdrawal for as long as two weeks (US prescribing information for naltrexone tablets).

Opioid overdose after stopping. The label warns that people may be more sensitive to opioids, even at lower doses, after naltrexone is stopped, that fatal overdoses have been reported after treatment ended, and that attempts to overcome the blockade with large opioid doses are especially dangerous; the label does not address low doses (US prescribing information for naltrexone tablets).

Emergency pain care. The label states that in an emergency needing opioid pain relief, people on fully blocking doses may need more opioid than usual, with deeper and longer depression of breathing, and that reactions such as facial swelling, itching and bronchoconstriction may occur; the label does not address low doses (US prescribing information for naltrexone tablets). A case report described unresponsiveness after a small oxycodone dose in a person on low-dose naltrexone (PMID: 28410920).

Liver disease. The label warns of hepatitis and clinically significant liver dysfunction, reports about 5- and 10-fold higher naltrexone exposure in compensated and decompensated cirrhosis, and notes that adequate studies in severe liver or kidney impairment have not been done (US prescribing information for naltrexone tablets).

Kidney impairment. Naltrexone and its main metabolite leave the body mainly in urine, and the label advises caution in kidney impairment (US prescribing information for naltrexone tablets).

Depression. The label reports depression and suicidal thinking after marketing in people treated for opioid dependence, with no causal relationship shown, and calls for monitoring (US prescribing information for naltrexone tablets).

Pregnancy, breastfeeding and children. The label reports no adequate human studies in pregnancy, unknown passage into human milk, and no established safe use under 18 years of age (US prescribing information for naltrexone tablets).

Interactions

7 pairings in our record: 3 to avoid, 3 with a caution and 1 to monitor.

Opioid pain medicines
Avoid

Naltrexone blocks opioid receptors, so opioid pain relief may be blocked, and the naltrexone label lists people receiving opioid pain medicines as a contraindication. In an emergency, the label says people on fully blocking doses may need more opioid than usual and breathing may be depressed more deeply and for longer; the label does not address low doses (US prescribing information for naltrexone tablets). A 2017 case report described the reverse: a man on low-dose naltrexone became unresponsive after a single 5 mg dose of oxycodone and needed naloxone (PMID: 28410920).
Methadone and buprenorphine
Avoid

People maintained on methadone or buprenorphine are contraindicated in the naltrexone label; naltrexone can bring on withdrawal severe enough to need hospital care, and people switching from these drugs may be vulnerable for as long as two weeks (US prescribing information for naltrexone tablets).
Naltrexone-bupropion (Contrave)
Avoid

The label for the naltrexone-bupropion weight-management tablet says coadministration with other naltrexone-containing products is not recommended (US prescribing information for naltrexone-bupropion extended-release tablets).
Opioid-containing cough, cold and antidiarrheal medicines
Caution

The naltrexone label says people taking naltrexone may not benefit from opioid-containing cough and cold preparations, antidiarrheal preparations or pain relievers (US prescribing information for naltrexone tablets).
Bremelanotide (Vyleesi)
Caution

The bremelanotide label says bremelanotide may significantly decrease exposure to orally administered naltrexone and advises avoiding it with oral naltrexone products intended to treat alcohol or opioid addiction; the label does not address low-dose use (US prescribing information for bremelanotide).
Disulfiram and other potentially liver-toxic drugs
Caution

The naltrexone label says the safety of combining naltrexone with disulfiram is unknown and that using two potentially liver-toxic medicines together is not ordinarily recommended unless the probable benefits outweigh the known risks; this comes from standard-dose labeling (US prescribing information for naltrexone tablets).
Thioridazine
Monitor

Lethargy and somnolence have been reported after doses of naltrexone and thioridazine (US prescribing information for naltrexone tablets).

This interaction data is compiled from published research and community reports. It may not be exhaustive. Always consult a healthcare professional before combining compounds.

Need bloodwork before starting?

Full hormone + metabolic panels from Anabolic Insights. Code CHONCH for first-order discount.

Order Bloodwork

04Dosing

Free with email

Dosing

No dose on record

Our record lists no dose for Low-Dose Naltrexone (LDN). This section holds what it does list.

Dosing summary

Route: Oral

Unlock the Dosing section

Enter your email to keep reading. It is free, and it opens these sections on every compound page in this browser.

Route

You also get the free peptide cheat sheet by email. Unsubscribe anytime.

Have an account? Sign in

05Prices

Low-Dose Naltrexone (LDN) prices

No listings

We do not track a vendor for Low-Dose Naltrexone (LDN) yet, so this page states no price.

06Chemistry

Chemistry and structure

Molecular formula: C20H23NO4
Molecular mass: 341.4 g/mol
CAS number: 16590-41-3
Half-life: About 4 hours for naltrexone and 13 hours for its main metabolite, 6-beta-naltrexol (mean elimination half-lives in the US prescribing information for naltrexone tablets, which describes standard doses). No half-life was calculated in a 2023 fibromyalgia trial that measured blood levels after 4.5 mg (PMID: 38226027).

View on PubChem

08Questions

Frequently asked questions

What is low-dose naltrexone (LDN)?

Low-dose naltrexone (LDN) is naltrexone, an opioid receptor antagonist approved by the FDA for alcohol and opioid dependence, used off-label at doses far below the 50 mg tablet (US prescribing information for naltrexone tablets and for extended-release injectable naltrexone; PMID: 42060160). Reviews define low-dose naltrexone as about 1 to 5 mg a day (PMID: 30248938, PMID: 40962192). The smallest single-ingredient naltrexone tablet approved in the US is 25 mg, and low-dose naltrexone is commonly prepared by compounding pharmacies (Drugs@FDA; PMID: 40962192).

Is low-dose naltrexone FDA approved?

Low-dose naltrexone is not FDA approved for any condition (Drugs@FDA). Naltrexone tablets were first approved on 20 November 1984 and are labeled for alcohol dependence and for blocking the effects of opioids (Drugs@FDA NDA 018932; US prescribing information for naltrexone tablets). An extended-release naltrexone injection, approved on 13 April 2006, is labeled for alcohol dependence and for preventing relapse to opioid dependence (Drugs@FDA NDA 021897; US prescribing information for extended-release injectable naltrexone). Prescribing naltrexone at low doses for fibromyalgia, Crohn's disease, multiple sclerosis or long COVID is off-label use (PMID: 42060160).

Does low-dose naltrexone work for fibromyalgia?

In a 31-woman crossover trial at Stanford, low-dose naltrexone at 4.5 mg a day reduced daily pain by 28.8 percent against 18.0 percent on placebo (PMID: 23359310). In the two largest placebo-controlled fibromyalgia trials, low-dose naltrexone did not reduce pain more than placebo, in 99 women given 6 mg a day for 12 weeks in Denmark and in 98 women given 4.5 mg a day in Spain (PMID: 38258677, PMID: 42385209). A reanalysis of pain scores from four randomized low-dose naltrexone trials by the investigators of the Danish FINAL trial found no significant effect on pain after 3 or 12 weeks (PMID: 41469218).

What did the Crohn's disease trials of low-dose naltrexone find?

In a 2011 Penn State trial in 34 adults with active Crohn's disease, 88 percent on low-dose naltrexone 4.5 mg a day had at least a 70-point fall in disease activity at 12 weeks against 40 percent on placebo (PMID: 21380937). A 2018 Cochrane review rated the evidence on low-dose naltrexone in Crohn's disease as low quality and insufficient for firm conclusions (PMID: 29607497). A Dutch multicenter trial of low-dose naltrexone in Crohn's disease stopped early for futility after 41 patients, with endoscopic remission in 5.6 percent on low-dose naltrexone against 18.8 percent on placebo (PMID: 42701992).

Is there evidence for low-dose naltrexone in long COVID?

A 2026 systematic review found no randomized trials of low-dose naltrexone in long COVID, only four uncontrolled before-and-after studies with 155 patients, and rated the certainty of evidence as low (PMID: 42463201). A placebo-controlled trial of low-dose naltrexone for post-COVID fatigue in British Columbia enrolled 160 participants and was completed on 28 February 2026, according to ClinicalTrials.gov, and no results had been published in PubMed by 21 October 2026 (PMID: 38740499; NCT05430152).

How does low-dose naltrexone interact with opioids?

Naltrexone blocks opioid receptors, and the naltrexone label lists people taking opioid pain medicines, people dependent on opioids including those on methadone or buprenorphine, and people in opioid withdrawal among its contraindications (US prescribing information for naltrexone tablets). Naltrexone given to someone who is not free of opioids can bring on withdrawal, usually within five minutes, and some reported cases needed hospital or intensive care admission (US prescribing information for naltrexone tablets). The naltrexone label warns that people may be more sensitive to opioids after naltrexone is stopped and that fatal overdoses have been reported after treatment ended (US prescribing information for naltrexone tablets). A 2017 case report described a man taking low-dose naltrexone for multiple sclerosis who became unresponsive after a single 5 mg dose of oxycodone and needed naloxone (PMID: 28410920).

What are the side effects of low-dose naltrexone?

In a 99-woman fibromyalgia trial of low-dose naltrexone, 84 percent on low-dose naltrexone and 86 percent on placebo reported an adverse event, and 8 percent against 6 percent stopped because of one (PMID: 38258677). A 2025 meta-analysis of fibromyalgia trials found vivid dreams more often with low-dose naltrexone than with placebo, with a risk ratio of 2.41 (PMID: 40337423). Sleep disturbance, headache, nausea, fatigue and mild diarrhea were recorded in low-dose naltrexone trials (PMID: 17222320, PMID: 38226027, PMID: 34014028). The naltrexone label warns of liver injury that it describes as dose related, and in a 34-patient Crohn's disease trial of low-dose naltrexone, 2 patients on naltrexone had transient transaminase rises that resolved within a month (US prescribing information for naltrexone tablets; PMID: 21380937).

Price check

No vendor listings yet

We do not track a vendor for Low-Dose Naltrexone (LDN) yet.

Compare other compounds

Spec sheet