In 1984, an endocrinologist named Bernard Bihari, who was treating people with cancer and other immune-related disorders, noticed that naltrexone, an FDA-approved treatment for alcohol dependence and drug addiction, also demonstrated anti-inflammatory properties.

At standard doses, the drug’s common side effects included nausea, vomiting, and headaches, so Bihari decided to experiment with smaller amounts. When he administered a much lower dose of naltrexone than usual (~3 mg), the results were impressive — patients experienced a decrease in pain and inflammation without any of the typical side effects.

Bihari’s research team went on to run studies on a variety of autoimmune diseases, including fibromyalgia, Crohn's disease, and multiple sclerosis. The results were positive: patients reported significant improvements in their symptoms and quality of life. The findings led Bihari and his colleagues to conclude that low-dose naltrexone (LDN) could be "an alternative to the current pharmacological armamentarium" and could be used as a new therapy for autoimmune diseases.

Since then, low-dose naltrexone has been gaining traction as a viable alternative to the standard treatments for autoimmune diseases. Unlike many other drugs, LDN is mostly free of side effects and may provide significant symptom relief without the adverse reactions that often come with conventional medications. 

This article will cover the basics of how LDN works, how it's used, and why it's gaining popularity.

What Is Low-Dose Naltrexone, and Why Would I Take It? 

Low-dose naltrexone is a non-toxic drug used to treat autoimmune diseases. It's a form of a drug commonly used for treatment of opiate addiction and overdose. Low-dose naltrexone has been used to treat conditions related to autoimmunity, including multiple sclerosis, rheumatoid arthritis, and Crohn’s disease. On the surface, it may look like naltrexone has little to do with autoimmune disease, but studies have shown that low doses of the drug can affect anti-inflammatory mechanisms in the brain. (Source)

How Does Low-Dose Naltrexone Work in the Body?

LDN operates as an "immunomodulator"

Naltrexone helps to balance the immune response by activating opioid receptors in the brain and gut. These receptors activate a "reset" button in the immune system, preventing it from attacking the body's own tissues. In fact, the drug is believed to work by inhibiting the pro-inflammatory immune cells that contribute to these conditions. (Source)

It blocks the effects of opioids at the cellular level

It's an opioid antagonist, which means it works by blocking the activation of opioid receptors. For this reason, naltrexone is used as a maintenance treatment to modulate and control opioid cravings, while also inhibiting the effects of opioids when they are used. (Source, Source)

It enhances the endorphin system

‍Autoimmune patients tend to have lower levels of endorphins, the body’s natural pain-relieving and mood-boosting chemicals. LDN works by promoting the release of endorphins. By increasing endorphin levels, LDN can help to reduce inflammation and improve mood, which can help to ease symptoms of depression. Furthermore, when endorphin levels reach a certain threshold, the immune system can begin to regulate. (Source)

It reduces inflammation in the central nervous system

‍Studies have shown that LDN can suppress the activity of cells in our brains called microglia. Microglia are the primary immune cells in the central nervous system that produce inflammation in response to pathogens or injury. When activated, these “white blood cells” of the brain can release inflammatory chemicals, causing a host of symptoms, including fatigue, reduced pain tolerance, sleep and mood disturbances, and cognitive disruption. (Source)

What Does the Research Show?

Despite promising evidence, the use of LDN for chronic diseases is still highly experimental. Although there are no current FDA-approved uses for LDN, providers are still able to prescribe it for indicated uses. Existing trials have small sample sizes, so more research is needed and results need to be reproduced.

Low-Dose Naltrexone and Autoimmune Conditions

The scientific literature suggests LDN may be a promising treatment option for people living with a number of different autoimmune disorders, although research continues.

LDN may reduce Crohn’s disease activity

Of all the autoimmune conditions, Crohn’s is the one that has been studied in the majority of trials with the drug. Some studies have reported positive results, but sufficient evidence regarding the efficacy of LDN in active Crohn’s disease is still lacking. In 2007, the first published LDN trial in humans found that 89% of participants with active Crohn’s disease responded positively to the drug, with 67% achieving remission. The most common side effect was sleep disturbances, which occurred in 41% of participants. Another randomized control trial from 2013 found that disease activity improved in 67% of children treated with LDN, and 25% went into remission. Both of these trials were with small sample sizes (Source, Source)

Overall quality of life improvements have been demonstrated for multiple sclerosis, but the findings are limited

‍In one study of patients with multiple sclerosis, researchers found that low-dose naltrexone helped patients more with their mental health than their MS symptoms. While this is still a significant finding, it goes to show how experimental the treatment still is, while also providing a glimpse of some promising possibilities for the future. (Source)

Pilot studies for systemic sclerosis have had promising results

‍Pruritus, or itchy skin, is one of the symptoms of systemic sclerosis, an autoimmune disorder that causes an overproduction of collagen and other proteins. Pruritis is difficult to treat, and there is some indication that LDN may mitigate this symptom. In a small pilot study of three participants, patients with systemic sclerosis saw significant improvements in both GI and pruritus-related symptoms after taking LDN, with two patients fully resolving their pruritus during the trial. More research is needed, especially larger RCTs, but initial results are encouraging. (Source) 

Low-Dose Naltrexone and Hashimoto’s Disease

Anecdotal evidence suggests LDN may improve symptoms of Hashimoto's disease. Although studies are limited, some patients have reported positive improvements to their condition after taking LDN, including reduced fatigue, lethargy, and aches. Others, however, seem to have no response at all. While LDN is a promising potential treatment option for Hashimoto’s, there simply isn’t enough research yet to support any firm conclusion. (Source) 

Low-Dose Naltrexone and Fibromyalgia

LDN may improve quality of life in fibromyalgia patients. In 2013, a randomized controlled trial of 31 fibromyalgia patients found significant improvements in pain, mood, and general satisfaction with life in the LDN group compared to placebo. (Source) 

Low-Dose Naltrexone and Other Conditions

Studies have also looked at LDN as a possible treatment option for non-autoimmune conditions such as autism (Source), neuropathic pain (Source), depression (Source), and complex regional pain syndrome (Source). These studies were all limited by being small in size, but did show LDN as potentially beneficial. Larger studies are needed to further investigate the use of LDN for these additional diagnoses. 

Similar to Hashimoto’s, anecdotal reports and case studies suggest low-dose naltrexone may be helpful for some patients with chronic fatigue syndrome and myalgic encephalomyelitis, but no clinical trials have been carried out so far. (Source)

Is Low-Dose Naltrexone Safe?

Although LDN has been used in clinical practice for more than 15 years, the FDA has not approved it for any indication. Low-dose naltrexone is an off-label prescription medication, which means it hasn’t been federally approved for autoimmune treatment or any other diagnosis. However, the LDN Research Trust funds clinical trials designed to demonstrate the safety and efficacy of LDN.

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What Are Potential Side Effects of Low-Dose Naltrexone?

Most people who try LDN experience no side effects at all, although some do report insomnia, vivid dreams, and anxiety. In general, the side effects of low-dose naltrexone are typically mild and can often be reduced by using the lowest effective dose. 

Some of the most common side effects of LDN are:

• Headache
• Bloating
• Dizziness
• Sleeplessness
• Fatigue
• Nausea
• Dry mouth
• Diarrhea
  

These side effects are usually mild and tend to go away after a week or two.

Other, less common, side effects of LDN are:

• Runny nose
• Insomnia
• Muscle aches
• Rash
• Difficulty urinating
• Low blood pressure
• Weight loss
  

Some people experience a feeling of euphoria (a "high") when they begin taking LDN. This feeling is generally not long-lasting. LDN is not likely to cause the side effects that are typical of opiate drugs, such as constipation, respiratory depression, and a "nodding" effect. It's not clear whether LDN causes birth defects, so it's best not to use it if you're pregnant.

At very high doses, LDN may cause liver damage or other serious side effects. Although some side effects have been reported at dosages in the range of 6.5 mg to 9.0 mg, these side effects are extremely rare.

How Much Low-Dose Naltrexone Do I Take?

This depends on several factors, including:

• Your body weight
• Your diagnosis
• The severity of your condition
• Your individual body chemistry
• The dosage recommended by your health care provider
• The specific form of LDN that you are taking
  

Your health care provider will help you decide on a proper dosage for you, and if relevant, the best way to take the medication. There’s no standard dose for LDN, although therapeutic doses typically range between 1.5 mg and 4.5 mg. It’s important to start with the lowest possible effective dose to minimize side effects.

LDN is usually taken at or near bedtime, but if you have trouble sleeping your health care provider may recommend you take it in the morning instead.

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What Are Natural Alternatives To Low-Dose Naltrexone?

There is evidence that some foods may work as immunomodulators, similar to LDN. During digestion, these “functional foods” release bioactive peptides, or small protein fragments, that can bind with opioid receptors throughout the body. Research suggests these peptides, found in foods ranging from milk to spinach, can have beneficial effects such as pain relief, reduction of anxiety, and regulation of immune function. (Source, Source)

More research is needed to understand how these peptides can operate as therapeutic agents, but they offer a promising new type of exogenous opioids, or exorphins, to complement the body’s naturally occurring endorphins.

How Can I Get Low-Dose Naltrexone?

Although LDN can seem like an unusual or novel treatment option at first glance, accessing the treatment is a simple process, and LDN will work just like any other medication you’ve been prescribed. 

In the US, health care providers are allowed to prescribe medications off-label, so your provider should be able to give you a prescription if they think LDN will be a good fit for you. You will need to have your prescription filled at a compounding pharmacy, which can create a custom formulation from the standard 50mg naltrexone tablets. Not every pharmacy has this ability, but it shouldn’t be hard to find a compounding pharmacy in your area.

Low-Dose Naltrexone for Autoimmune Conditions: What’s the Bottom Line?

Low-dose naltrexone, which binds to opioid receptors throughout the body, may act as an immunomodulator and may have beneficial effects in many autoimmune diseases. It’s too soon to say it is a definitive treatment for any medical condition, but the outlook is promising.

Research into the effects of and possible uses for low-dose naltrexone is ongoing, and even more targeted, effective formulations may become available as we learn more. In the meantime, it is a potential treatment option to keep on your radar if you have an autoimmune condition.

Before proceeding with LDN treatment, think about whether you feel comfortable pursuing a treatment option that has yet to receive official approval, and talk to your health care provider about whether there are other treatments that may work better for you.

Disclaimer: LDN is still a highly experimental treatment and is not FDA-approved for pain or any other indication. This post discusses scientific research for informational purposes only. If you are interested in LDN, talk to your health care provider about its possible effectiveness, side effects, and risks.