Low-Dose Naltrexone (LDN)

How it works

At very low doses, naltrexone briefly blocks opioid receptors for a few hours each night. The body is thought to respond by increasing its own endorphins and enkephalins, including met-enkephalin (“opioid growth factor”), which supports mucosal healing through the OGF receptor. LDN also moderates Toll-like receptor 4 on immune cells, reducing inflammatory cytokine release. It is a fascinating example of an old medication being repurposed to support the body’s own healing systems.

Traditional use

Not a traditional remedy. Naltrexone was approved in 1984, and its low-dose use was pioneered by Dr. Bernard Bihari in the 1980s. It has since built a large patient-led community across autoimmune and inflammatory conditions.

Highlights

• In a randomised trial of 34 people with moderate-to-severe Crohn’s, LDN was associated with improved clinical and endoscopic response.
• Supports the body’s own endorphin and opioid-growth-factor systems, which are involved in mucosal healing.
• Inexpensive, off-patent and generally very well tolerated.
• One more recent trial found reduced fatigue — a symptom that matters enormously to quality of life.
• Requires a prescription and is usually made by a compounding pharmacy.

What the research shows

Every study below links to its original publication so you can read it yourself. Many natural compounds have only been studied in small trials. That isn’t a verdict on them; it reflects how little funding exists for compounds that can’t be patented.

Using it alongside conventional care

LDN is a powerful example of why our community exists. A prescription medication that costs a few dollars a month showed encouraging Crohn’s results, but because naltrexone is off-patent, no company has reason to fund the large trials that biologics like Humira, Remicade, Stelara, Skyrizi and Entyvio receive. Cochrane describes the current evidence as promising but too limited for firm conclusions. That is the kind of gap real-world patient data can help fill. LDN requires a prescription, and it blocks opioid pain medication, so it needs planning around any surgery or procedure.

Never stop or change a prescribed medication without your gastroenterologist. Many people use natural support alongside conventional care, and your care team can help you do that safely.

Amounts used in research

Trials used 4.5 mg/day orally, typically at night, for 12 weeks. Paediatric trials used 0.1 mg/kg. This requires a prescription and, in most countries, compounding — it is not a supplement.

Good to know

• Generally well tolerated; vivid dreams and sleep disturbance are the most common effects, usually transient.
• Blocks opioid analgesia — a critical consideration in a population that may need post-operative or acute pain management.
• Contraindicated with ongoing opioid use; can precipitate acute withdrawal.
• Requires liver function monitoring; naltrexone carries hepatotoxicity warnings at standard doses.
• Must be prescribed and supervised; the dose requires compounding and is not an over-the-counter option.

Community experiences

Sources

1. 1

   Therapy with the opioid antagonist naltrexone promotes mucosal healing in active Crohn’s disease: a randomized placebo-controlled trial

   Smith JP, Bingaman SI, Ruggiero F, et al. · Digestive Diseases and Sciences · 2011 · PMID 21533868

2. 2

   Low dose naltrexone for induction of remission in Crohn’s disease

   Parker CE, Nguyen TM, Segal D, MacDonald JK, Chande N. · Cochrane Database of Systematic Reviews · 2018 · PMID 29607497

3. 3

   Low-dose naltrexone in Crohn’s disease: a prematurely terminated randomized trial showing reduced fatigue without clinical or endoscopic benefit

   Recent randomised controlled trial · Digestive Diseases and Sciences · 2026