What LDN is, and its FDA status
Naltrexone blocks opioid receptors. At 50 mg it is FDA-approved to treat alcohol dependence and to block the effects of opioids, and the label says it has not been shown to provide benefit except as part of a plan to manage those addictions (naltrexone label, DailyMed).
Low-dose naltrexone means daily doses of roughly 1 to 5 mg (Toljan and Vrooman, Med Sci 2018, PMID: 30248938). Any use at those doses for pain, inflammation or other conditions is off-label, and the small capsules are usually compounded, so they are not FDA-approved products.
This article is general information, not medical advice or a dosing recommendation. Decisions about starting, changing or stopping a prescription belong with a licensed clinician who knows your history.
How it might work
At standard doses naltrexone simply blocks opioid receptors. Researchers propose that low doses work differently: by calming inflammatory signaling in the nervous system’s microglial cells (via Toll-like receptor 4) and by briefly blocking opioid receptors, which may prompt the body to raise its own endorphin signaling (Younger et al., Clin Rheumatol 2014, PMID: 24526250; Toljan and Vrooman, 2018).
These are hypotheses supported mostly by laboratory and small clinical studies. The same review that proposed the microglial mechanism describes LDN use for chronic disorders as “still highly experimental” (Younger et al., 2014).
What the trials show
| Condition | Trial | Result |
|---|---|---|
| Fibromyalgia | 31 women, crossover, 4.5 mg (2013) | Pain fell 28.8% on LDN vs 18.0% on placebo |
| Fibromyalgia | 99 women, randomized, 6 mg for 12 weeks (2024) | No significant pain difference vs placebo |
| Crohn’s disease | 40 adults, 4.5 mg for 12 weeks (2011) | 88% had a 70-point activity drop vs 40% on placebo |
| Crohn’s disease | Cochrane review of 2 trials, 46 people (2018) | Remission not significantly different; evidence low quality |
| Multiple sclerosis | 80 enrolled, crossover, 4.5 mg for 8 weeks (2010) | Better mental-health quality-of-life scores |
Fibromyalgia is the best-studied use, and the results conflict. The 2013 crossover trial found less daily pain than placebo (Younger et al., Arthritis Rheum 2013, PMID: 23359310). The larger 2024 Danish trial found no significant difference in pain (between-group difference −0.34 points, p = 0.27), although it suggested a possible effect on memory problems worth studying (Due Bruun et al., Lancet Rheumatol 2024, PMID: 38258677).
Crohn’s disease: a 40-patient trial reported clinical and endoscopic improvement (Smith et al., Dig Dis Sci 2011, PMID: 21380937). The Cochrane review found that remission rates were not significantly different (30% vs 18% in adults), response rates favored LDN, and the evidence was too sparse for firm conclusions (Parker et al., Cochrane 2018, PMID: 29607497).
Multiple sclerosis: a pilot crossover trial found improvements in mental-health quality-of-life measures, but dropouts and data errors cut its statistical power (Cree et al., Ann Neurol 2010, PMID: 20695007).
Across all of these, trials are small and few have been replicated. LDN is not a substitute for established treatment of any of these conditions.
Safety: the opioid interaction comes first
The naltrexone label lists these contraindications: taking opioid pain medicines, current opioid dependence (including methadone or buprenorphine), and acute opioid withdrawal. Naltrexone can trigger withdrawal in anyone with opioids in their system (DailyMed).
• Tell every clinician, dentist and surgeon that you take naltrexone, including before procedures where opioid pain relief might be used.
• The label warns that after stopping naltrexone, people may be more sensitive to opioids, raising overdose risk.
• In the Crohn’s trials, side effects such as sleep disturbance, unusual dreams and headache were not significantly more common than on placebo (Parker et al., 2018), and LDN was rated as tolerable as placebo in the 2013 fibromyalgia trial.
This article is general information, not medical advice or a dosing recommendation. Decisions about starting, changing or stopping a prescription belong with a licensed clinician who knows your history.
Cost and online options
Compounded LDN is sold through telehealth plans that include a clinician visit; current prices are on low-dose naltrexone online. HealthRX is one approved partner that offers LDN; see our HealthRX review and the telehealth comparison hub.
Disclosure
CalcMyPeptide may earn commissions from some telehealth providers on our comparison and review pages, which list only vetted providers whose affiliate programs have approved us or are reviewing our application. This article contains no paid links. How we rank providers and get paid: telehealth disclosure and methodology.