What is Low Dose Naltrexone (LDN)?

LDN is a safe, non-toxic and inexpensive drug that helps regulate a dysfunctional immune system.

It reduces pain, and fights inflammation. It is used to treat cancers, autoimmune diseases, chronic pain and mental health issues, to name a few. Treatment is constantly evolving, with new conditions and methods of treatment being shared regularly.

In 1984 Naltrexone was approved by the FDA in the USA for the treatment of opioid addiction, used at the standard dose of 50mg to 100mg per day. It is a pure antagonist at various opioid receptors, Delta Kappa, Mu, and Opioid Growth Factor (OGF) receptors.

LDN is a competitive opioid receptor antagonist. At the standard dose, naltrexone blocks the effects of both the endogenous opioids, which are in endorphins and pharmaceutical opioids. LDN is a pure antagonist, which is vital to know as a lot of people think it is a controlled medicine, narcotic or an opioid.

LDN is a pure inhibitor, so there is no narcotic effect. The chemical structure is almost identical to endorphins that we make naturally called met-enkephalin, also known as OGF or Opioid Growth Factor.

LDN is an antagonist at the OGF receptors and there are OGF receptors on a wide range of cells in the body.  When we talk about low dose naltrexone we mean doses that are a 10th or less of the standard dose of Naltrexone. Most of the research studies have used 4.5mg per day. Doses range from 0.001mg – 16mg in clinical practice.

Low Dose Naltrexone binds to the endorphin receptors for about 1 – 1/2 hours, and the blockade lasts about 4 - 6 hours. The effects of LDN are analgesia and anti-inflammatory.  One of the other effects is that it increases the production of your own endorphins.

Research into the effects of LDN began in the 1980s by Dr. Ian Zagon and Dr. Patricia McLachlan at Penn State. Dr. Bernard Bihari, in New York was the pioneer of using LDN in clinical practice. In the mid-1980s he was using it to treat HIV in his patients. His patients were taking Naltrexone for their opioid addictions and as he weaned them off it he noticed positive side effects with other conditions and symptoms. He was a Harvard trained physician who was a specialist in neurology. He was running the New York State health department, and he was aware of the research that was going on and tried it out for clinical use.

The first published human trial was in 2007 by Dr. Jill Smith, it was a study for Crohn's disease.

  • Naltrexone exists in a racemic mixture of isomers ("left-handedness and right-handedness")
  • Dextro-naltrexone binds toll-like receptors (TLR)
  • Levo-naltrexone binds opioid receptors

Dextro-naltrexone

  • Antagonist effect at Toll-like receptors (TLR)
  • TLR-4 receptors exist on microglial cells, other macrophages, mast cells
  • Activated microglial cells produce proinflammatory cytokines, substance P, nitric oxide
  • Inhibition leads to a decreased proinflammatory cascade

Levo-naltrexone

  • Antagonist effect at opioid receptors
  • Small temporary opioid blockade
  • Upregulates endogenous opioid production
  • Upregulates opioid receptors
  • Increased endorphins favourable to the immune system

Endorphins are your natural peptides produced in many cells which regulate cell growth, including your immune cells. Many patients who have autoimmune disease tend to have low levels of endorphins, Met-enkephalin, aka opioid growth factor (OGF), an important immunomodulatory. Opioid receptors are in the central and the peripheral nervous system, the GI tract, and on lymphocytes. By using LDN you receive a brief blockade, creating a rebound effect giving you more endorphins, including OGF, and increased production of the OGF receptors.