Most sources on low-dose naltrexone (LDN) in chronic pain and other conditions are reviews, small trials and observational studies, and the reviews describe the evidence as limited. A 2026 narrative review of 105 LDN studies says early positive findings from uncontrolled studies were rarely replicated in placebo-controlled trials. A result in one condition does not carry over to another.
Randomized trials
Two single-condition randomized trials are described here. Neither reported support for LDN on the measure it studied.
- Arthritis pain: a small pilot was randomized, double-blind, placebo-controlled and crossover, with 4.5 mg LDN for 8 weeks. Its findings do not support LDN being efficacious in reducing nociceptive pain due to arthritis. Too few patients were enrolled to rule out modest benefit or to assess inflammatory or neuropathic pain.
- Major depressive disorder: a 12-week randomized, double-blind, placebo-controlled trial tested LDN (up to 4.5 mg per day) added to antidepressants in 37 patients. The abstract says adjunctive LDN does not appear to alter depressive symptoms in moderate MDD.
Observational and open-label studies
These designs cannot show cause and effect. Several report adverse effects and people stopping.
| Study | Dose | What it reported |
|---|---|---|
| Open-label pilot, irritable bowel syndrome, 42 patients, 4 weeks | 0.5 mg PTI-901/day, described as low-dose NTX | Global assessment improved in 76% of 42 patients. |
| Retrospective cohort, academic pain clinic | <10 mg for at least one month | 87% (27) of patients discontinued LDN: 52% (16) for lack of benefit, 23% (7) for loss of benefit, 10% (3) for side effects, 3% (1) for other reasons. Seven (23%) reported side effects. |
| Retrospective chart review, chronic pain, Veterans | Not stated in the abstract | 32% (13 of 41) reported adverse effects including vivid dreams, drowsiness, dizziness, and nausea. |
| Retrospective cohort, chronic pain, one physician's practice | Not stated in the abstract | Adverse effects occurred in 49.5% of patients, most frequently nausea and fatigue. No serious adverse effects were reported. |
| Single-centre pre-post study, Post COVID-19 Syndrome | 1 mg month one, 2 mg month two | Thirty-eight participants (73.1%) were known to commence LDN. Two (5.3%) stopped due to new onset diarrhoea and also described fatigue. |
| Before-after study, hypothyroidism, 898 patients, Norwegian Prescription Database | Not stated in the abstract | The results do not support claims of efficacy of LDN in hypothyroidism. |
Reviews
A 2014 review says that, despite initial promise of efficacy, the use of LDN for chronic disorders is still highly experimental, with low sample sizes and few replications. A 2018 review of LDN in multiple sclerosis, fibromyalgia, Crohn's disease and other chronic pain disorders says the studies reviewed demonstrate subjective benefits over placebo, but evidence for more objective measures is limited. It says evidence supports safety and tolerability, that fewer studies support efficacy (most using subjective measures such as quality of life or self-reported pain), and that further randomized controlled trials are needed because evidence supporting its use in those diseases is insufficient. A 2023 fibromyalgia systematic review says proving the efficacy and safety of LDN is a future possibility, but the level of scientific evidence is limited. A 2025 meta-analysis of randomized trials in chronic pain syndromes (dose not stated) reported that adverse events were increased with LDN compared to placebo.
Some reviews found no randomized trials or few articles. A 2026 long COVID systematic review found no randomised controlled trials among 397 titles and abstracts screened. Four observational pre-post studies (n=155) met inclusion, with LDN doses from 1 mg/day to 6 mg/day. A complex regional pain syndrome review found limited articles on that condition, so most studies it analyzed covered other chronic pain syndromes.
The 2026 narrative review says most evidence consists of case reports and small feasibility studies prone to publication bias and reliant on subjective outcomes. It describes LDN as well tolerated, with most studies using 4.5 mg daily, but says current evidence does not support routine clinical use.
Disclosures in these sources
The conflict of interest statement for the Post COVID-19 Syndrome study says one author reports financial support was provided by UCD Foundation (Gilead, Pfizer, GSK Newman Fellowship). The statement for the arthritis pilot says one author reports research funding from Gilead and paid consulting with ChemoCentryx, HIBio, and Genentech. The statement for a 2023 scoping review of LDN in non-cancer centralized pain conditions says one author is a consultant for Swing Therapeutics and Scilex Pharmaceuticals. These are disclosures only and do not show that any result was affected.
What this does not tell you
These sources do not establish benefit of LDN for chronic pain or any other condition. The conditions, doses, designs and lengths differ, and several abstracts do not state the dose, so a result in one condition says nothing about another. Observational and open-label studies cannot show cause and effect, and the reviews describe the trials they cover as small. Reports of adverse effects here come from different groups and doses and cannot be compared directly. A licensed provider decides what is suitable for a given person.