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Health and Medical

What are the 3 main mechanisms of action of LDN

Mechanisms of Action

There are different mechanisms of action of LDN that have been listed in the literature. The 3 of the most notable actions of LDN are mentioned below:

  1. acts on opioid receptors to boost the release of β-endorphins
  2. capacity to decrease pro-inflammatory cytokines and enhance anti-inflammatory cytokines
  3. regulates the opioid growth factor (OGF) and opioid growth factor receptors (OGFr) axis

Production of endorphins and opioid receptor activation

Bihari mentioned in his analysis that the release of endogenous endorphins in the body takes place between 2:00 am – 4:00 am. However, another research has revealed that beta (β)-endorphins are discharged in healthy adults from 4:00 am to 10:00 am. Beta-endorphins attach to mu (μ) opioid receptors. This synergy between μ receptors and β-endorphins is considered to be useful for the analgesic results in the body. The word endorphin originates from “endogenous morphine.” Endorphins are naturally present in the human body and form from the methyl group of L-methionine and the amino acid L-tyrosine.

Morphine, the medicine, is the exogenous form of opioid which is similar to our endogenous opioids. Morphine is obtained from the plant opium poppy, the family Papaver somniferum, and is being used for several years because of its analgesic qualities. Endogenous morphine is produced by the adrenal gland and is discharged from the liver. It has been revealed to raise after the body goes under physical stress like sepsis and operation. In addition to enhanced levels of endogenous morphine, higher levels of anti-inflammatory cytokines are also released in response to stresses like surgery.

As stated, naltrexone in increased doses is categorized as an opioid receptor antagonist and inhibits the receptors to prevent the effects of medicines like morphine. Higher doses of naltrexone also have been displayed to limit the endorphin release after physical activity. Contrasting to higher doses of naltrexone, Low Dose Naltrexone performs its action on β-endorphin receptors to excite the discharge of endorphins in the body. Low-dose naltrexone is still regarded as an opioid receptor antagonist, however just for a brief duration, and experimentation has revealed that LDN raises endogenous opioids levels. Furthermore, Low Dose Naltrexone spurs the body’s endorphin production, even if there’s no LDN in the system.

Anti-inflammatory activity

The rise of β-endorphins in order to decrease pain levels is just one aspect of the application of LDN therapy in pain management, particularly when the cause of the pain is linked with an inflammatory process. It has been confirmed that LDN decreases inflammation by decreasing multiple pro-inflammatory cytokines. Cytokines are biochemical messengers/carriers, usually produced by immune cells, whose exclusive result can be either an increase or decrease in immune function. The synchronization of the immune system depends on the body’s capability to maintain a balance among cytokines that result in inflammation and cytokines that decrease it.  Various cells in the body produce cytokines that are linked with the physiological sensation of pain. Though, the cytokine system isn’t an easy process. For instance, tumor necrosis factor-alpha (TNF-α) is linked with both enhanced swelling and neuroprotection when the body encounters an outrage such as nerve damage. Excessive production or upregulation of TNF-α is related to some conditions like cerebral ischemia, atherosclerosis, and Alzheimer’s disease, and decreasing levels of this cytokine might be of interest in treatment.

In a pilot study using 4.5 mg LDN every night, serum levels of various proinflammatory cytokines such as interleukin (IL)-1, IL-2, IL-12, IL-18, interferon-gamma (IFN-γ), TNF-α and, granulocyte-macrophage colony-stimulating factor (GM-CSF) were greatly decreased when compared to baseline in subjects experiencing fibromyalgia.

Regulation of the opioid growth factor

Low-dose naltrexone has proved to upregulate the OGF/OGFr axis. The opioid growth factor, also known as [Met5]-enkephalin, is an opioid peptide. The title was changed to OGF because of the relationship of [Met5]-enkephalin with cell growth and proliferation. Cell growth cycles are categorized into different stages which are

  • G1 – before DNA synthesis
  • S – DNA synthesis
  • G2 – before mitosis
  • M – mitosis or cell division

OGF has been seen to put on hold the G1/S phase of the cell cycle. Additionally, there is data that confirms that the OGF/OGFr axis pathway is linked with the regulation of tumor growth. The application of LDN therapy to control this pathway holds importance in cancer study and treating neurodegenerative disorders like multiple sclerosis. Furthermore, research has revealed that cell proliferation is modified when OGF attaches to the OGF receptors. Due to the upregulation of the OGF/OGFr axis pathway, tumor growth can be reduced.

Treating pain can be a complex trial but the patient can benefit from an option that involves consideration of both physiological and psychological features of a patient’s symptoms. Healthcare providers have various tools at their avail when confronting the challenge of pain management. Managing the symptoms of pain with LDN as a single option of therapy might not always work. But, if the patient’s health situation is very inflammatory (like rheumatoid arthritis) making use of LDN can be greatly helpful in itself.



Harbor Compounding Pharmacy in California to provide better health solutions. This medical pharmacy is working in all major states of the USA. The aim of this health pharmacy is to provide solutions to all health-related issues. To maintain work-life balance, it provides treatment for all diseases and health counseling.

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