Low Dose Naltrexone (LDN) & Lyme

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Updated: 3/21/23

About Low-Dose Naltrexone for Lyme

Low-dose naltrexone (LDN) is very useful in Lyme disease. This low-cost medicine can

  • improve nerve, muscle, and inflammation pain,
  • decrease autoimmune illness triggered by Lyme,
  • improve mast cell activation symptoms,
  • lower cytokine inflammation, and
  • improve immune system function by increasing TRegs to balance Th1 and Th2.

In this article, I review the science and method for how LDN works. I describe how to use it in Lyme disease, and I review potential side effects.

What is Low-Dose Naltrexone (LDN)?

Naltrexone is an opioid receptor blocker. Narcotics, such as oxycodone found in Percocet and hydrocodone found in Vicodin, are opioids. When they bind to an opioid receptor, narcotics regulate pain. Humans make natural narcotics called endorphins. These endorphins regulate pain and the immune system.

Low-dose naltrexone (LDN) is “low” because it is used at much lower doses than physicians use to treat people with narcotic overdose and alcoholism. LDN is manufactured only as a 50 mg pill. When it is used to regulate the immune system, it is dosed at 1.5-4.5 mg a day.

Compounding pharmacies that make medicines in-house produce naltrexone in low doses by crushing the 50 mg pill and dividing it into to “low” dose 1.5-4.5 mg pills.

How Does LDN in Lyme Disease Work?


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LDN Effects through Endorphin Receptors

At low doses, LDN attaches to opioid receptors on a temporary basis of around four hours. Sensing the blockade, the body produces more endorphins and more endorphin receptors. The existing endorphin receptors also become more sensitive to endorphins.

The increased endorphins caused by the LDN blockade help with pain, but they also decrease immune system hyperactivity. This is the type of immune overactivity where the immune system attacks a person’s tissues leading to ongoing inflammation, like in rheumatoid arthritis. It is also the type of activity where chronic infections trigger an overproduction of inflammation cytokines. These cytokines are the cause of most Lyme disease symptoms. See Control Cytokines: A Guide to Fix Lyme Symptoms and the Immune System for more information.

Cytokines decrease on LDN as the immune system shifts away from a Th1 inflammation pattern to more of a Th2 inflammation pattern. Th1 inflammation occurs when white blood cells that fight infections, like T cells, become too turned on. Th2 inflammation is more commonly seen in allergic-type reactions or when antibodies attach to germs. T regulatory white blood cells (TRegs) create balance between Th1 and Th2. When someone is taking LDN, these TRegs work better.

LDN Effects on Toll-like Receptors

White blood cells use Toll-like receptors (TLRs) to recognize germs like bacteria and viruses. A type of white blood cell in the brain is microglia. If its TLRs are turned on too much, and ongoing, it can lead to neuropathic (nerve) pain. This could explain some of the pain felt throughout the whole body in people with multiple sclerosis, for instance, or in Lyme disease. The turning on of TLRs is one theory why people with fibromyalgia have ongoing pain throughout the body.

TLRs are also on mast cells. Some with Lyme develop mast cell activation syndrome (MCAS), leading to ongoing health problems. See Mast Cell Activation Syndrome & Lyme for more information.

Furthermore, LDN binds directly to the TLRs. When bound, bacteria and other stimulators of these receptors are blocked. LDN does not activate the TLRs but does provide an effective blockade.

Therefore, LDN in Lyme disease can help nerve pain, fibromyalgia-like pain, and even regulate mast cells in MCAS.

A Word About Pain

There are three ways LDN in Lyme disease helps pain.

  • One reason LDN may help pain is that the increased endorphins bind to a greater number of endorphin receptors, which are more sensitive. In other words, a person’s natural narcotics work better.
  • LDN lowers cytokine inflammation, and
  • LDN blocks Toll-like receptors to regulate nerve-generated pain, which includes fibromyalgia-type pain.

Does LDN work?

Limited science shows LDN helps in fibromyalgia, multiple sclerosis, and Crohn’s disease. Based on case reports and discussions with healthcare providers, LDN seems to help many more conditions.

For more detailed information about conditions treated and the reasons why LDN works, read The LDN Book published by the LDN Research Trust. The LDN Research Trust is building a scientific basis for LDN and promoting its health-saving benefits for a variety of conditions.

Unfortunately, no one has studied if or how LDN benefits Lyme disease.

So what do I know? 

In my Seattle practice, I find LDN helpful in autoimmune illnesses like rheumatoid arthritis, Hashimoto’s thyroiditis, ulcerative colitis, lupus, and others. I also see LDN help in multiple sclerosis.

At one time, I did not see much benefit in using LDN for most Lyme patients, but I have changed my opinion. I used to have people try it for three months. If a person did not see improvements, I would have them stop. I have now come to realize that this medication takes time to work. In fact, when I use it in patients for six months or more, I find benefits for many people with Lyme.

When to Use LDN in Lyme Disease

There are four situations to use LDN in a Lyme disease treatment.

  • Use it at the beginning of treatment when someone has another autoimmune illness, such as lupus or rheumatoid arthritis.
  • If a person is 6-9 months into treatment following The Ross Lyme Support Protocol and their improvements are small, try LDN.
  • In Mast Cell Activation Syndrome, LDN can decrease mast cell hyperreactivity.
  • If a person has completed Lyme disease antibiotics, but many symptoms remain, try LDN. For some, chronic Lyme infection triggers an autoimmune illness that LDN can regulate. Additionally, in some, Lyme triggers an ongoing cycle of cytokine inflammation that LDN can break.

How to Take LDN in Lyme Disease

Start at 1.5 mg a day for two weeks, then at 3.0 mg for 2 weeks, and finally at 4.5 mg a day on an ongoing basis. Because it can cause insomnia in some, take it in the morning.

If a person has a lot of side effects or gets worse with their symptoms initially, then decrease the dose to half of the above. Often the side effects will go away by lowering the dose.

  • Common neurologic side effects include: anxiety (15.7 percent), drowsiness (11.6 percent), headache (11.6 percent), insomnia (8.3 percent), muscle pain (8.3 percent), vivid dreams (5 percent), mood change (3.3 percent), and trouble with concentration (1.7 percent).
  • Additional side effects include: nausea (12.4 percent), abdominal pain (11.6 percent), diarrhea (8.3 percent), and anorexia (8.3 percent).


The ideas and recommendations on this website and in this article are for informational purposes only. For more information about this, see the sitewide Terms & Conditions.


View Citations

  1. Younger J, Parkitny L, McLain D. The use of low-dose naltrexone (LDN) as a novel anti-inflammatory treatment for chronic pain. Clin Rheum. 2014;33(4):451-459. doi:10.1007/s10067-014-2517-2 (View)
  2. Patten DK, Schultz BG, Berlau, DJ. The safety and efficacy of low‚Äźdose naltrexone in the management of chronic pain and inflammation in multiple sclerosis, fibromyalgia, Crohn’s disease, and other chronic pain disorders. Pharmacotherapy. 2018;38: 382-389. doi:10.1002/phar.2086 (View)
  3. Ploesser J, Weinstock LB, Thomas E. Low dose naltrexone: Side effects and efficacy in gastrointestinal disorders. Internat J Pharm Compd. 2010;14(2):171-173. (View)
  4. Elsegood L. The LDN Book: How a Little-Known Generic Drug—Low Dose Naltrexone—Could Revolutionize Treatment for Autoimmune Diseases, Cancer, Autism, Depression, and More. Chelsea Green; 2016.
  5. Weinstock L, Cottel J. Low Dose Naltrexone and Autoimmune Disease Therapy. Lecture presented at the Institute for Functional Medicine Annual International Conference; 2018; Hollywood FL.
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About The Author

Marty Ross, MD is a passionate Lyme disease educator and clinical expert. He helps Lyme sufferers and their physicians see what really works based on his review of the science and extensive real-world experience. Dr. Ross is licensed to practice medicine in Washington State (License: MD00033296) where he has treated thousands of Lyme disease patients in his Seattle practice.

Marty Ross, MD is a graduate of Indiana University School of Medicine and Georgetown University Family Medicine Residency. He is a member of the International Lyme and Associated Disease Society (ILADS), The Institute for Functional Medicine, and The American Academy of Anti-Aging Medicine (A4M).

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