Low-Dose Naltrexone and Dietary Changes for the Treatment of Autoimmune Diseases

Story at-a-glance

  • Naltrexone is an opiate antagonist, originally developed in the early 1960s for the treatment of opioid addiction. When taken at very low doses (LDN), it triggers endorphin production, which can boost your immune function
  • Gluteomorphins (from gluten) and caseomorphins (from casein) act as exogenous opioids that suppress immune function. Hence an autoimmune diet needs to be free of gluten and dairy
  • LDN is most effective when combined with an autoimmune diet, free of gluten and dairy, rich in fresh and fermented vegetables, with low to modest amounts of high-quality protein


This is an older article that may not reflect Dr. Mercola’s current view on this topic. Use our search engine to find Dr. Mercola’s latest position on any health topic.

By Dr. Mercola

Most people are aware that drugs are not an ideal solution to their health problems, but there are some exceptions to this rule.

Dr. Thomas Cowan, a family physician and founding board member of the Weston A. Price Foundation (WAPF), is a strong proponent of using low-dose naltrexone (LDN) for autoimmune diseases.

What Is Naltrexone?

Naltrexone is an opiate antagonist, originally developed in the early 1960s for the treatment of opioid addiction (such as heroin), which was prevalent at that time. It blocks the effects of the narcotic by attaching to opioid receptors in your body.

"Naltrexone is a pure opiate antagonist; meaning it has no agonist. Agonist means it has a positive effect. It has no agonist effect. It has no analgesic effect. There's no euphoria. There's no high. It simply blocks the opiates," Cowan explains. 

For heroin overdoses, a dose of about 30 to 50 milligrams (mg) of naltrexone was, and still is, used to prevent the fatal respiratory depression from a narcotic overdose.

However, the drug not only blocks exogenous narcotic opiates. Many drug users refused to take naltrexone because it made them feel terrible, and this led to the discovery of endorphins.

Endorphins are endogenous opiates, meaning they're not introduced from the outside. They're naturally produced by your body. This was why people suffered dysphoria (the opposite of euphoria) when taking naltrexone, as the drug blocked the natural opioids (endorphins) as well.

The Discovery of Low-Dose Naltrexone and Its Benefits

Dr. Bernard Bihari1 began taking an interest in naltrexone in the late 1980s, as many of his addicted patients also had immunological problems. Many of them had AIDS, which is a cell-mediated immune collapse.

He observed that virtually the only patients dying from HIV infection were those using opiates. He wondered whether endogenous opiates might have something to do with immunological function, which has since been shown to be the case in thousands of studies.

"He decided that maybe these people with immunological problems have endorphin deficiencies," Cowan says. "That led him to try to figure out a way to stimulate endorphin production.

He [discovered that] if you use a very low dose of naltrexone, you block the opiate receptors for maybe an hour or so, and then your body responds by upregulating its synthesis of opiates.

You end up with a hundred or a thousand times more endorphins and a better-functioning immune system."

Essentially, when using a very LOW dose, about one-tenth of the dose you'd use for opioid addiction, or less, naltrexone works like a form of hormesis, which is when a compound that is toxic at high doses ends up having the converse effect in small or minute doses.

"LDN is probably the only pharmaceutical medicine I routinely use," Cowan says. "I have seen more people get better with that medicine than any other medicine I've ever used.

When you look at natural medicine, for instance: ginseng stimulates adrenal cortical function. It doesn't actually do anything itself; it just stimulates your adrenal gland to make something. That's typically how natural medicines work. That's the whole philosophy of homeopathy.

Similarly, even though it's not actually a 'natural medicine,' LDN stimulates endorphin production. It doesn't actually do anything positive itself. The patient has to respond.

If they don't respond, you don't get an effect. If they do respond and they make more endorphins, like they would have had with a natural medicine, then you get a positive effect from a normal amount of endorphin production."

LDN Dosing Recommendations

The normal range for LDN is between 1.5 and 4.5 mg per day, taken about an hour before bedtime (not in the morning). There are a couple of reasons for this timing.

First, since you're blocking endorphins, doing it in the middle of the night prevents you from noticing that you feel lousy. Second, the endorphin response is greater at nighttime. As for side effects, LDN has an enviable safety profile. The most common side effect is unusual and sometimes more vivid dreams.

Cowan typically starts patients out at 1.5 mg for two weeks. Sensitive people, such as those with thyroid problems, may start as low as 1 mg per day, but as a general rule, doses lower than 1.5 mg/day tend to be ineffective for most adults.

If there's a positive effect, the patient will stay on that dose. If there's no effect, the dose is increased to 3 mg per day. If there's a negative effect, the dose is decreased.

If there's a positive effect at 3 mg, stay on that dose. If there's still no effect, raise it to 4.5 mg, and if there's a negative effect, decrease the dose. That said, the key to LDN is the low dose. So many times you may actually need to lower the dose if you don't notice a beneficial effect.

"If you gave somebody 2.5 mg and it didn't work, lower the dose. You gave him 1.5 mg and it didn't work, give it every other day," Cowan says. "Because the principle is it's the rebound that's the positive effect, not the drug. With normal drugs, if it doesn't work you give more, but here, it's the opposite."

Opiates Are Potent Immunosuppressive Drugs

A famous study called the European Prostitute Study showed the primary risk factor for HIV and AIDS was not sexual exposure, not IV exposure, but opiate exposure.

According to Cowan, you see a similar pattern in cancer patients. As soon as they start taking opiates for chronic pain, their health rapidly declines as their immune system falters.

"Opiates are highly immunosuppressive medicines," he explains. "What I mean by opiates is exogenous opiates; opiates from the outside. Bihari saw that. He saw that the people that were getting AIDS were opiate addicts. And not just that, but that was a certain subset.

Since endorphins are essentially the flipside of exogenous opiates, meaning endogenous opiates, what you're doing is substituting the good guys for the bad guys.

... In the late '90s, I had a very good friend who was diagnosed with terminal lymphoma. He actually knew Bihari. Bihari put him on 4.5 mg of LDN. He did IV vitamin C, and he went into remission. I went to Hawaii on vacation with them about three years ago. That's something like 15 years later. That was a situation that got my attention big time."

Cowan's Autoimmune Diet

Aside from opiate drugs like heroin and prescription painkillers, your diet can be a source of exogenous opiates. Many natural health physicians recommend removing wheat and dairy from the diet, as these foods tend to trigger complications in a large number of people.

What many don't realize is that part of the problem stems from the fact that gluteomorphins (from gluten) and caseomorphins (from casein) act as exogenous opioids.

"Basically, when you're doing this diet ... you're getting rid of exogenous opiates. It's really about getting rid of exogenous opiates (the ones that downregulate and cause dysfunction of your immune system) and then upregulating the endogenous or healthy endorphins," Cowan says.

Virtually anyone suffering with an autoimmune problem, be it multiple sclerosis (MS), inflammatory bowel disease (IBD), or Hashimoto's (autoimmune thyroid disease), just to name a few, would be wise to try a gluten- and dairy-free diet to help optimize immune function. (Grass-fed ghee can be used, as it's very low in casein.) 

In Cowan's experience, and he's prescribed LDN for at least 1,000 patients, the autoimmune diet or LDN alone are typically not nearly as effective as the two combined. Besides avoiding or eliminating gluten and dairy, his dietary recommendations are very similar to the Gut and Psychology Syndrome (GAPS) Diet.

"It's basically getting rid of the exogenous opiates and repairing the gut flora [with] fermented foods," Cowan says. "The Cowan Autoimmune Diet is animal foods that are low to modest in protein; seeds, but no grains for a while, and a diversity of vegetables and fermented foods."

Consider Eating a Wider Variety of Vegetables

Fresh vegetables, which are high in fiber, also help heal your gut by nourishing healthy microbes. Some bacteria also create short-chain fatty acids from the fiber, which are important for your health. One key is variety and diversity. Most Americans eat perhaps a dozen different kinds of vegetables in any given year, whereas our ancestors ate hundreds of different varieties.

Part of the problem is that most people only have access to seasonal vegetables sold in the grocery store. To amend this situation, Cowan grows his own. He has a large garden with about 60 different vegetable varieties, some of which are perennial, such as tree collards (collard greens that grow on trees).

"They're sort of deep green, deep purple vegetables. They live for about 12 to 15 years and withstand even down to about 10 degrees Fahrenheit. They'll withstand frost.

There's the perennial chard, which is the genetic precursor of beets and Swiss chard. There's Ashitaba. There's Gynura, which is Okinawa spinach. That's the spinach that is supposedly reputed to be why the Okinawans live so long. It has a chemical in it that has an effect similar to metformin. It's an anti-diabetic, essentially nutrient-rich food."

I believe anyone fully committed to health will inevitably and invariably come to the conclusion that they have to grow their own food, and pay attention to the soil quality. Aside from being hard to find commercially, perennial vegetables have the distinct advantage of growing and producing year-round.

"I recently read a statistic from the Food and Drug Administration (FDA): People who eat three to four different parts of the plant per day — we're talking about the root part, the leaf part, and the flower or fruit part; those are fundamental parts — have 40 percent less chronic disease than people who don't do that. I believe that.

We don't need vegetables for calories, fats and proteins. That's the role of the other foods in the diet. We eat them for phytonutrients, fiber to feed the microbiome, vitamins, minerals, things known and unknown.

Therefore, to eat a huge bowl of Romaine lettuce is sort of a waste of vegetable power. You want to have a salad with as many colors as you can get, as many parts of the plant as you can get, as much diversity as you can get. That's the role of vegetables in the traditional diet," Cowan says.  

"I would absolutely encourage everybody to grow their own vegetables. [My book even contains] the science of when vegetables are the most nutritious.

For example, zucchini should be eaten within a couple of hours after picking it, because the sugars degrade and the nutrients degrade, whereas lettuce actually likes it to be injured a little bit and then sit around for about 12 hours, so it actually makes more reactive chemicals to essentially heal itself. It's better eaten after about 12 hours."

More Information

In Cowan's experience, LDN can be an incredibly valuable healing aid. Many suffering with autoimmune diseases like MS, ulcerative colitis, Crohn's disease, pemphigus, or Graves' disease, for example, have been able to significantly improve or go into remission by incorporating LDN and changing their diet to avoid exogenous opioids found in wheat and dairy, and improving their gut health and nutrition with fermented and fresh vegetables.

Good resources where you can learn more about LDN and find doctors who use it include LowDoseNaltrexone.org and LDNScience.org. Linda Elsegood's book, "The LDN Book: How a Little-Known Generic Drug Low Dose Naltrexone Could Revolutionize Treatment for Autoimmune Diseases, Cancer, Autism, Depression, and More" is another great resource.

To learn more about growing and eating vegetables, pick up a copy of Cowan's new book, "How (& Why) to Eat More Vegetables." You can also find more information on his website, drcowansgarden.com.

+ Sources and References

By continuing to browse our site you agree to our use of cookies, revised Privacy Policy and Terms of Service.