We have found Low Dose Naltraxone (LDN) to be useful in the treatment of patients with dysautonomia. This is most likely because LDN has an immune modulation and anti-inflammatory effect on migroglia, the inflammatory cells found within the nervous system. LDN is often prescribed to our patients as part of a integrative treatment program that may include transvascular autonomic modulation (TVAM), mesenchymal stem cell (MSC) therapy, and other treatments.
Small intestine bacterial overgrowth (SIBO) is a very common comorbidity of dysautonomia seen in our patients. This is in large part a result of alteration in normal peristalsis of the gut. Peristalsis contractions are strongly influenced by opiate receptors. Opiate antagonists like naltrexone have been shown to have pro kinetic effects. LDN plays an important role in improving peristaltic function (gut function) as an integral component of SIBO treatment regimen.
What is LDN and How Does it Work?
Naltrexone is a reversible competitive opiate receptor antagonist. It has a Plasma half life of 6 hours being almost fully eliminated in 24 hours. At full dose of 50mg to 150mg per day naltrexone is used for opiate addiction. Dosages in the range of 1.75mg to 4.5mg per day is described as Low Dose Naltrexone (LDN). LDN is well tolerated with a good safety profile. Administration of naltrexone as LDN results in transient blockage of the opioid receptor. This leads to increased production of endogenous opioids (endorphins) and enkephalin via positive feedback. The endorphin and enkephalin elevations persist beyond the transient period of LDN binding.
A specific enkephalin, Met(5)-enkephalin, is increased by LDN is also known as opioid growth factor (OGF). OGF is a endogenous peptide which stimulates production of opiate receptors, specifically OGFr, potentiating the effect of endorphins. The OGF-OGFr axis regulates the cell cycle impacting cell proliferation. LDN therefore has immune modulatory effect with both T and B cell inhibition. These effects have led to usage of LDN in a variety of neurodegenerative disorders including multiple sclerosis and fibromyalgia.
Toll like receptors (TLR) are proteins that are an important component of the immune system. TLR4 is an example of one that is predominantly associated with microglia, which are the cells responsible for inflammation in the nervous system. TLR4 expression is increased in a number of neuroinflammatory conditions resulting in the production of inflammatory cytokines such as IL6, TNF alpha and NF-kappaB. LDN blocks the TLR4 receptor inhibiting microglial activation and cytokine production. Microglia have been implicated in dysautonomia, particularly multiple symptom atrophy (MSA).
Pioneering the Use of LDN in Dysautonomia Patients
We are among the first to prescribe LDN as a treatment for patients with dysautonomia and/or SIBO. While we continue to see positive clinical results in our patients, further study of the use of LDN will lead to better understanding of it’s therapeutic potential.