Naltrexone is a drug that was first discovered in 1963 to block opioid receptors. In 1984 naltrexone was approved by the FDA for alcohol and opiate addiction. At doses of 50-100mg, naltrexone blocks opiate receptors and prevent the euphoric sensation of alcohol or opiate drug consumption.
Low dose naltrexone (LDN) has been used for a variety of conditions associated with immune system dysregulation since the 1980s. Physicians that specialize in chronic Lyme disease have discovered low dose naltrexone (LDN) is effective at improving the immune response associated with Lyme disease.
What is Low Dose Naltrexone(LDN)?
In 1985 Dr. Bernard Bihari was working with HIV/AIDS patients in New York City. The human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS) that is characterized by the destruction of the immune system. Dr. Bihari was aware of the research that demonstrated naltrexone could improve the immune system, so he performed studies using low doses of naltrexone (LDN) in people with HIV/AIDS. The results showed LDN strengthened the immune system, and fewer of his patients died when they took LDN.
Dr. Bihari’s work sparked interest in LDN by other researchers, and many additional research studies were conducted over the ensuing years. Dr. Ian Zagon’s research has been instrumental in understanding the connection between low-dose naltrexone and the immune system. His work confirmed LDN’s effect on opiate receptors, and endorphin release is involved in most biological pathways that regulate the immune response in humans.
How Does LDN Work?
At the manufactured dose of 50mg for alcohol and opiate addiction, naltrexone completely blocks opiate receptors. Dosages of 0.5mg to 4.5mg are referred to as “low-dose” naltrexone (LDN) and have different physiological effects on the human body.
Low-dose naltrexone partially blocks opiate receptors, which in turn increases endorphin production. Endorphins help to regulate the immune system. LDN has become an important therapy for inflammatory conditions and chronic infections because immune system dysregulation is a hallmark feature. Also, endorphin levels tend to be low in autoimmune diseases, so increasing endorphins with LDN may improve the outcome of autoimmune conditions.
LDN is also known to bind to a class of immune system receptors called toll-like receptors (TLRs). When bacteria, viruses, or other foreign substances bind to TLRs, an inflammatory cascade is triggered. LDN works by blocking toll-like receptors to inhibit the production of inflammatory cytokines.
One study evaluated the use of LDN for eight weeks for the treatment of fibromyalgia. After the administration of LDN, multiple inflammatory cytokines were significantly reduced. The cytokines included interleukin-6 (IL-6), transforming growth factor-beta (TGF-b), and tumor necrosis factor-alpha (TNF-a). Additionally, pain associated with fibromyalgia reduced after taking LDN.
LDN Decreases Inflammation in the Brain
The primary immune cells that protect the brain and spinal cord are called microglia. The microglia survey the central nervous system for foreign invaders such as bacteria, viruses, and toxins such as mold. When the microglia encounter one of these threatening invaders, an inflammatory response is triggered.
Microglia possess toll-like receptor 4 (TLR4), which are part of this inflammatory cascade. LDN binds to TLR4 and blocks downstream neurological inflammation. I have found LDN to be one of the most effective therapies for my patients who have immune dysregulation and inflammation-causing symptoms of the brain, including headaches, anxiety, depression, and brain fog.
What Conditions Does Low Dose Naltrexone (LDN) Treat?
Because LDN modulates the immune system and reduces inflammation, it is effective in a variety of conditions and symptoms. Below is a list of symptoms and conditions I routinely treat with LDN:
- Autoimmune conditions
- Lyme disease and associated infections
- Epstein-Barr virus
- Mold illness
- Chronic fatigue syndrome
- Mast cell activation syndrome (MCAS)
- Joint pain
- Nerve pain (neuropathy)
- Leaky gut syndrome
- Small intestine bacterial overgrowth (SIBO)
Low Dose Naltrexone (LDN) for Lyme Disease
Persistent low-grade infection with the Borrelia bacteria characterizes chronic Lyme disease. Many of the symptoms associated with chronic Lyme disease are due to a persistent immune response and not directly from the bacteria. Successful treatment of late-stage Lyme disease requires treatments directed at the infection(s) and improving the immune response.
The inflammatory cytokines IL-6, TNF- alpha, and TGF-beta, are elevated in Lyme disease. When used to treat Lyme disease and co-infections, low dose naltrexone reduces these cytokines and the associated inflammation. Immune deficiency is another common issue in chronic Lyme disease. This contributes to frequent illnesses and interferes with the body’s ability to fight the bacteria that causes Lyme disease. Through the endorphin-promoting action of LDN, immune system function improves.
How is Low Dose Naltrexone Taken?
Naltrexone is manufactured in 50mg tablets, so it must be compounded by a compounding pharmacy to get lower doses. I typically start patients on 0.5mg-1mg once per day at night. Then they increase the dose each week by one capsule at night until they reach 4mg at night. If a patient’s symptoms are better on a dose lower than 4 mg, they should stay on the lower dose for a more extended period of time.
It may take 3-6 months to notice the benefits of LDN. In my experience, this medication is one of the most effective treatments for a majority of my patients with symptoms rooted in chronic inflammation and immune dysregulation. It is necessary to give LDN some time to work on these underlying causes.
Side Effects of Low Dose Naltrexone
The FDA approved naltrexone in the 1980s, so it has a long track record with an excellent safety profile. At much lower doses than the manufactured 50mg dose of naltrexone, compounded low-dose naltrexone has very few adverse effects.
To coincide with the body’s natural nighttime increase in endorphin production, LDN is typically taken at bedtime. For some people, LDN can contribute to insomnia. Often insomnia can be prevented if the dose of LDN is started lower than the target dose and titrated up as described above. If insomnia continues after titrating the dose, some people benefit from taking LDN in the morning instead of at night.
Since naltrexone partially blocks opioid receptors, LDN cannot be taken with opioid pain medications. The exception to this is the use of “ultra” low dose naltrexone (doses less than 1 microgram) to improve the effect of opioid pain medications.
Possibly the Least Expensive, Most Effective Therapy for Conditions Related to Immune Dysfunction and Inflammation
There are few medications available that are safe, inexpensive, and effective for chronic inflammation and immune-related conditions. When properly prescribed, LDN has the potential to improve the quality of life for people suffering from symptoms from Lyme disease, mold illness, and other chronic inflammatory states.
“LDN could be the most significant, most underutilized therapy in all of medicine.” – Peter Koshland, pharmacist, founder Koshland Pharm