LDN and the Immune System

LDN and the Immune System

In this article, we will explore:

  1. What Met-enkephalin is and how it impacts the immune system
  2. How LDN increases Met-enkephalin levels and why it is important
  3. Positive effects of increased Met-enkephalin levels
  4. Chronic Inflammation is a sign of weakened immune system
  5. How LDN reduces inflammation

What is Met-enkephalin?

When we experience pain, our body releases chemicals to lower the pain. These same chemicals are also released when we do something pleasant, like exercise or listen to music. These chemicals are called opioids. Met-enkephalins are one of these opioids and are found mainly in the adrenal gland and throughout the Central Nervous System. Met-enkephalins bind to opiate receptors that release controlled levels of pain, as well as regulate memory and emotional conditions, food and liquid consumption, and the immune system. (1)

Like most biological processes, however, Met-enkephalin levels naturally decrease with age and stress. Autoimmune disorders, such as multiple sclerosis, can also cause Met-enkephalin levels to decrease at a faster rate.

How can we increase Met-enkephalin levels and reduce future stress? Low Dose Naltrexone (LDN) may be the answer.

Evidence LDN Increases Met-enkephalin Levels

Met-enkephalin Shows Positive Effect on Immune Cells

LDN is a widely used off-label therapeutic prescribed for a variety of immune-related disorders. In part, LDN works to intermittently block opioid receptors, resulting in increased endorphin release, modulation of the immune system, and reducing inflammation. (2)

A two-part study in 2017 concluded that “serum Met-enkephalin levels were lower in humans with multiple sclerosis relative to non-multiple sclerosis patients, and low-dose naltrexone restored their levels… Thus, Met-enkephalin may be a reasonable candidate biomarker for multiple sclerosis, and may signal new pathways for treatment of autoimmune disorders.”

Met-enkephalin Shows Positive Effect on Immune Cells

Numerous studies have indicated that Met-enkephalin displays the capacity to stimulate an immune response, having a positive effect on different types of immune cells.

For example, a 2014 study describes that Met-enkephalin was shown to enhance the number of T Cells (cells that play a critical part in immunity to foreign substances), which in turn improves host resistance to tumor growth or viral infections. (3)

Another study of 50 cancer patients, who were given Met-enkephalin boosters, concluded that Met-Enkephalin “could work as a strong immune booster with great potential in restoring damaged human immune system and we could consider MENK as a drug to treat cancer patients, whose immune systems are damaged by chemotherapy or radiotherapy. Furthermore we could consider MENK as a chemotherapy additive, which would sustain immune system of cancer patients during the process of chemotherapy to get maximized efficacy with minimized side effect.”

See the below illustration to visualize LDN’s effect on Met-enkephalin levels—which, in turn, can help strengthen the immune system and reduce other health risks:

 LDN’s effect on Met-enkephalin levels

For a full list of Met-enkephalin’s impact on the immune system, we invite you to reference an excerpt from the above-referenced 2014 study:

list of Met-enkephalin’s impact on the immune system

LDN Reduces Pro-inflammatory Cytokines
As you get older, your immune system weakens and chronic inflammation sets in. It has been shown that LDN reduces inflammation by reducing multiple pro-inflammatory cytokines.

In an 8-week single-blinded pilot study using 4.5 mg of LDN each night, serum levels of numerous proinflammatory cytokines including interleukin (IL)-1, IL-2, IL-12, IL-18, interferon gamma (IFN-γ), granulocyte-macrophage colony-stimulating factor (GM-CSF), and TNF-α were significantly reduced. By reducing inflammation, LDN, in turn, helps your immune system stay strong.

LDN & Met-enkephalin for Immunity

The clinical evidence supporting LDN’s effectiveness for a variety of conditions, including autoimmune diseases, is continuing to grow. As we have discussed in this blog, evidence to support LDN raises Met-enkephalin levels and further modulates the immune system (as noted above) further solidifies LDN as a safe, non-toxic, and inexpensive drug help countless patients with autoimmune diseases.

During the COVID-19 pandemic, LDN positions itself well as an immune-enhancing treatment. By increasing Met-enkephalin levels, thereby increasing the number of T Cells, it may help our bodies better armour up to fight off infection.

To learn more about LDN, or request a prescription, click here.


  2. Ludwig MD, Zagon IS, McLaughlin PJ. Featured Article: Serum [Met5]-enkephalin levels are reduced in multiple sclerosis and restored by low-dose naltrexone. Exp Biol Med (Maywood). 2017 Sep;242(15):1524-1533. doi: 10.1177/1535370217724791. Epub 2017 Aug 2. PMID: 28766982; PMCID: PMC5648293.
  3. Pomorska DK, Gach K, Janecka A. Immunomodulatory effects of endogenous and synthetic peptides activating opioid receptors. Mini Rev Med Chem. 2014;14(14):1148-55. doi: 10.2174/1389557515666150101095237. PMID: 25553430.
  4. Reduced Pro-Inflammatory Cytokines after Eight Weeks of Low-Dose Naltrexone for Fibromyalgia