Low-Dose Naltrexone (LDN): What It Is, Why People Choose It, and What the Research Shows

Low-dose naltrexone is an inexpensive prescription that many people with autoimmune conditions, chronic pain, and long COVID call life-changing. Here's how it's thought to work, what the trials show, and what to know before you ask your doctor.

MK Wellness InsightsFounded by Danielle Cordova, Cypress, TX

Low-dose naltrexone, or LDN, is one of the most talked-about tools in functional and integrative medicine. It's an old, inexpensive prescription drug used at a small fraction of its usual dose, and many people with autoimmune conditions, chronic pain, and long COVID describe it as life-changing.

Here's what it is, how it's thought to work, what the research shows, and what to know before you bring it up with your doctor.

What It Is

At its standard dose, naltrexone blocks the body's opioid receptors. The FDA approved it in 1984 to help people stay off opioids, and in 1994 for alcohol use disorder.

In the 1980s, New York physician Dr. Bernard Bihari began prescribing naltrexone at a small fraction of that dose, first for people with HIV/AIDS, and reported that it supported their immune systems. Since then, its use has spread to autoimmune conditions, chronic pain, and more. Using it this way is "off-label": the drug is FDA-approved, but not for these conditions or at this dose.

How It's Thought to Work

Researchers describe two main effects:

• A short block, then a rebound. A low dose blocks opioid receptors for just a few hours. The body responds by making more of its own endorphins and enkephalins, natural chemicals involved in pain relief and immune balance. Penn State researchers Ian Zagon and Patricia McLaughlin have spent decades studying this pathway (Experimental Biology and Medicine, 2018).
• Calming the nervous system's immune cells. At low doses, naltrexone also appears to quiet microglia, the immune cells of the brain and spinal cord, which can drive pain and fatigue when they're overactive. Pain researcher Dr. Jarred Younger, who led early LDN trials at Stanford, calls it one of the first "glial cell modulators" for chronic pain (Clinical Rheumatology, 2014).

Why People Choose It

• Autoimmune conditions. Many functional medicine doctors use it for Hashimoto's, multiple sclerosis, Crohn's disease, and other autoimmune conditions.
• Chronic pain. Especially fibromyalgia and complex regional pain syndrome.
• Long COVID and lingering fatigue. More doctors now prescribe it for fatigue, brain fog, and pain that won't lift.
• It's gentle and inexpensive. Side effects are usually mild, and it costs far less than most specialty drugs.
• It works with the body. Rather than overriding a system, it nudges the body to make more of its own calming chemicals.

What the Research Shows

• Fibromyalgia. In a Stanford crossover trial of 31 women, pain dropped 28.8% on LDN versus 18.0% on placebo, and mood and life satisfaction improved (Arthritis & Rheumatism, 2013). Pooling four trials with 222 patients, a 2024 review found significantly lower pain scores on LDN (Korean Journal of Pain, 2024). The largest single trial, from Denmark, didn't find less pain than placebo over 12 weeks in 99 women, though LDN may have helped memory problems (Lancet Rheumatology, 2024).
• Crohn's disease. In a placebo-controlled trial in adults, 83% improved on LDN compared with 38% on placebo, and 72% showed improvement on a scope compared with 25%. A Cochrane review called for larger trials to confirm it (Cochrane, 2018).
• Multiple sclerosis. In a UCSF trial, LDN improved mental health quality of life, the impact of pain, and self-reported thinking problems (Annals of Neurology, 2010).
• Rheumatoid arthritis, in real life. In Norway's national prescription records, people with rheumatoid arthritis who stayed on LDN used 13% less of their rheumatic medicines overall and 23% less pain medicine, and fewer needed DMARDs (PLoS One, 2019).
• Long COVID. A 2026 review of four early before-and-after studies found less fatigue, pain, and brain fog, and better sleep and daily function, on LDN (BMJ Open, 2026).

What to Know Before You Start

We don't share doses or protocols. Your prescriber sets those for you.

How to Find a Prescriber

LDN usually comes from a functional, integrative, or naturopathic doctor. A few places to start:

• The LDN Research Trust, a UK charity founded in 2004, keeps a prescriber directory and a pharmacy directory.
• The Natural Health Network directory helps you find holistic practitioners near you.

Common Questions

Is LDN the same drug used for addiction? Yes, at a much lower dose, which works differently in the body.

Is it FDA-approved for autoimmune disease? Naltrexone is FDA-approved, but not for these conditions or at this dose, so LDN is prescribed off-label.

How soon might I notice a difference? It varies from person to person. The trials ran 8 to 12 weeks, so ask your prescriber when to reassess.

Can I take it with my other medicines? It can't be combined with opioid pain medicines. Review everything else with your prescriber and pharmacist.

How This Fits at MK Wellness

We don't prescribe medicine. We support the terrain LDN works within:

• Our Autoimmune Support Toolkit walks you through labs, food, gut repair, and every option, step by step.
• PEMF, the infrared sauna, and the Sound Lounge support recovery and a calm nervous system.
• Gut Health and Autoimmunity: Repair, Then Rebuild covers the gut side of the story.

When you need something we don't offer, we connect you with people we trust.

Go Deeper

• LDN Research Trust: research summaries, plus prescriber and pharmacy directories
• Holistic Therapies: The Basics, for the short version of every therapy in this series
• The Autoimmune Support Toolkit
• Every holistic and alternative guide

MK Wellness services are non-medical and not intended to diagnose, treat, cure, or prevent any condition. This article is general education, not medical advice, and deliberately includes no doses or protocols. LDN is a prescription medicine; talk with a qualified prescriber about whether it's right for you.

The Autoimmune Support Protocol at MK Wellness

We build this goal around modalities that work better together. The core of the protocol:

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