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Can Low-Dose Naltrexone Treat Chronic Pain, Autoimmune Diseases, and Long Covid?

Can Low-Dose Naltrexone Treat Chronic Pain, Autoimmune Diseases, and Long Covid?

In the not-to-distant past, researchers experimenting with Naltrexone (a drug used to counter alcohol and opioid addiction) noticed something startling when tapering subjects off of the higher doses - reports of pain relief and symptom reduction. Scientists and doctors alike quickly surmised that Naltrexone might follow the "hormetic principle," that is, this drug has different effects at different dosage levels (1).

In the intervening years, low-dose Naltrexone (LDN) has been studied as a possible remedy or symptom-reducer for many conditions. Naltrexone acts in a way that causes the body to adapt, and the adaptation causes positive benefits (2). LDN has been studied in regard to autoimmune diseases, diseases involving inflammation, and even cancer (3). Every year, more applications of LDN are being found, including some recent indications that LDN is effective in cases of long-term infection (4).

Two properties of LDN provide most of the positive benefits the drug delivers. One property of LDN affects the inflammation response of the immune system while the other increases internal (natural) opioid production. Between the two, they can impact an impressive number of systems in the body. Keep in mind that uncontrolled inflammation as a response from the immune system is at the root of numerous chronic health conditions. Considering all these facts, it's unsurprising that doctors continue to find more applications for this versatile medication. So, what is it about LDN that makes it useful in various health conditions?

What is Low Dose Naltrexone?

Full strength Naltrexone is a medication that treats addiction disorders (3). Alcohol and opioid drugs work because they exploit the natural ability of our bodies to make similar molecules that ease pain. Opioid receptors exist in our bodies because we make our own chemicals that fit in those receptors and create particular reactions - pain relief and good feelings.

In treating alcohol and opioid use disorders, Naltrexone strengths of 50-100mg block the receptors involved in the pleasurable feelings the user seeks from alcohol and opioid drugs. Blocking the effects of alcohol and opioids removes the reward, which helps the user break the addiction.

Low-dose Naltrexone (LDN) provides a fraction of the usual dose, prescribed in quantities of 0.1mg - 6mg a day (1, 3). At lower doses, the effect is different. Instead of blocking receptors long-term, it only binds to the receptors briefly. This temporary blockage of the receptor site causes the body to reflexively make its own opioid (painkilling) molecules, creating a wave of natural pain relief (3).

Two main methods of action produce the vast majority of LDN's health benefits (1). The first is the ability of LDN to induce the body to create its own opioids. Notice that Naltrexone is not an opioid itself, so it is not considered addictive or likely to be abused (5). However, when an effective lower dose of Naltrexone is achieved, it will bind to receptors for 4 - 6 hours, causing the body to make its own opioid molecules for about 18 - 24 hours (3). Any condition that involves pain can benefit from this flood of internal opioids.

The second method of action produces anti-inflammatory effects. LDN interacts with microglial cells, which play a significant role in inflammation, especially inflammation of the nerves. When activated, microglial cells produce substances that create inflammation. The theory is that LDN blocks the receptors involved in activating microglia, so the activation is also blocked, resulting in fewer inflammatory chemicals. Any health condition driven by inflammation may benefit from this method of action.

What Conditions Can LDN Treat?

With the ability to decrease inflammation and raise internally made (endogenous) opioids, there are a vast number of health conditions that benefit from LDN. Below is only a partial list of conditions that LDN may address:

Fibromyalgia (1, 3, 6) - This complex disorder seems to magnify sensations of pain as well as produce memory and mood issues, fatigue, and disrupted sleep. Studies have shown a reduction in inflammation and improved "satisfaction with life and mood” (1), as well as a lowered baseline of pain level (6).

Autoimmune diseases - Autoimmune diseases occur as a result of the immune system mistakenly attacking something within itself, rather than defending against a "foreign" invader. LDN has a positive effect on many autoimmune diseases, including Crohn’s disease and Multiple Sclerosis.

  • Crohn's disease - This autoimmune-driven inflammatory bowel disease attacks healthy tissue from the small intestines down through the rest of the gastrointestinal tract. It can cause symptoms such as pain (usually in the abdomen) and debilitating diarrhea (7). Symptoms of fatigue, weight loss, and malnutrition may be primary or a result of diarrhea. Studies have shown solid symptom reduction in response to LDN (6, 8). One study showed that nearly 90% of the subjects using LDN to treat Crohn’s disease had a steep 70-point decline in a score that reflects the activity of the disease (3).

  • Multiple Sclerosis (MS) - In this autoimmune condition, the immune system mistakenly attacks the fatty covering of nerve fibers, creating a miscommunication between the brain and the body (11). Studies with LDN have shown overall symptom reduction (8), decreased spasticity and fatigue, and improved mental health (1).

Mast cell diseases - Mast cells defend the interior of the body from invaders and can get into a state of chronic activation or severe allergic responses. LDN can decrease the severity of mast cell activation syndrome (MCAS), bringing sufferers some much-needed relief (1).

Chronic infections - Since infections usually involve inflammation, and LDN counters inflammation, it makes sense that LDN would be a good ally in treating chronic infections.

  • Long COVID - Recently, the efficacy against a long-lasting infection was born out in a study involving long COVID, where symptoms persist long after the initial infection. Not only did LDN help reduce symptoms, but it also had a positive effect on clotting driven by the immune system (9). Certainly, these results are worthy of more investigation.

  • Small Intestine Bacterial Overgrowth (SIBO)- SIBO occurs when bacteria flourish in the small intestine, a place that usually has smaller numbers of bacteria due to its pH and other qualities. Bacteria growing in the "wrong place" can cause horrible diarrhea, abdominal cramping, and other symptoms.

  • Gastrointestinal diseases - There is some evidence that LDN improved cases of inflammatory bowel disease, including reducing the inflammation of intestinal linings (10). Success in Crohn's and ulcerative colitis (11) also indicates the usefulness of LDN in many types of gastrointestinal diseases.

Are There Any Side Effects?

Full-strength Naltrexone can have somewhat serious side effects (12). However, LDN offers such a low dose of the medication that the risk of side effects goes way down. Very few people experience side effects from LDN. However, if they do, it could include (3):

  • Problems sleeping or vivid dreams

  • Upset stomach

  • Rare cases of weight loss or painful prolonged erections

Sleeping difficulties tended to resolve after a few weeks (3), and the "wild dreams," only experienced by 1% of people (3), can be alleviated by slightly lowering dosage. Overall, LDN seems very well-tolerated and causes few side effects (3).

Pros and Cons of Taking LDN

Numerous conditions can be treated with LDN (1, 3). The lengthy list includes chronic pain, which can be tricky to treat without using heavy medications that are habit-forming.

Many groups of people can benefit from anti-inflammatory, endogenous opioid-boosting LDN, including those who have:

  • Chronic pain

  • Autoimmune conditions

  • Chronic systemic inflammation

  • Gastrointestinal conditions (Crohn's, SIBO, IBS, IBD)

  • Chronic allergic conditions or mast cell disorders

  • A chronic infection (SIBO, long COVID, Lyme disease or other tick borne infections, chronic viral infections like EBV)

LDN has a good safety profile (3) and is very unlikely to be habit-forming (5).

LDN is slow to reach an effective dose and show results. Most oral doses may take 8-10 weeks to show positive results (3). The long ramp-up time can cause some people to lose interest, but those who stick with it can be richly rewarded.

Long-term studies on LDN have not been performed. However, full-strength Naltrexone has been used safely for decades to treat opioid addictions (3).

Contraindications of Taking LDN:

Some groups of people have conditions that are made worse by the administration of LDN (3).

People who are currently taking opioid pain medications are not good candidates for taking LDN. Taking LDN and opioids simultaneously can cause immediate withdrawal from opioids which can be very problematic in certain circumstances.

Some people are sensitive to the medication or can have an allergic response to Naltrexone or other ingredients (adjuvant) that form the pill or liquid.

Those with liver issues such as cirrhosis must be carefully evaluated to determine risk, while those with acute hepatitis should probably be excluded from taking LDN.

Executive Physicals and Other Evaluations

Temecula Center for Integrative Medicine (TCIM) doctors perform in-depth health evaluations during our Executive Physicals. We aim to find and treat the root cause of illness and promote the prevention of chronic diseases. There are times when non-addictive, safe pain relief is an absolute necessity for quality of life. LDN can reduce pain and has the added possibility of elevating mood, reducing a wide variety of symptoms, and speeding the healing of tissue. If it's been a while since you've had your chronic pain or illness evaluated, or if your previous doctor did not do a "deep dive" with thorough blood panels and state-of-the-art screenings, please make an appointment for an Executive Physical. We may help you achieve the next giant leap in your health and give you the relief you've sought for so long.


Jonathan Vellinga, M.D.

Jonathan Vellinga, MD is an Internal Medicine practitioner with a broad interest in medicine. He graduated Summa cum laude from Weber State University in Clinical Laboratory Sciences and completed his medical degree from the Medical College of Wisconsin.​

Upon graduation from medical school, he completed his Internal Medicine residency at the University of Michigan. Dr. Vellinga is board-certified with the American Board of Internal Medicine and a member of the Institute for Functional Medicine.




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