LOW-DOSE NALTREXONE (LDN) FACT SHEET ABOUT LDN
Naltrexone is an opioid antagonist used primarily in the management of alcohol and
opioid dependence; the FDA approved Naltrexone in 1984 at 50mg. However, there is
“Accumulating evidence suggests LDN can promote health supporting immunemodulation,
which reduces various oncogenic inflammatory autoimmune processes.”1
The value of Naltrexone as an immune modulator was recognized by Dr. Ian Zagon at
the University of Pennsylvania.2,3 The late Dr. Bernard Bihari, a Neurophysician from
New York, USA (who passed away on May 16th, 2010) began treating his patients in the
late 1980s4,5. Since that time, many doctors throughout the United States prescribe LDN
for a number of indications including Multiple Sclerosis (MS), Parkinson’s disease,
Crohn’s disease, HIV/AIDS, cancer and other autoimmune and inflammatory diseases.
A number of research and clinical trials have been completed and undergone in regards
to LDN immunotherapies, with phase I and phase II clinical trials successfully run at a
number of universities in the United States and Europe, including Pennsylvania State
University Medical School at Hershey; University of Chicago; State University of New
York; SUNY Upstate Medical University; London Health Sciences Centre - University
Hospital, USA; Alpert Medical School of Brown University; Department of Neurology, San
Raffaele Scientific Institute; Division of Rheumatology, St. Louis College of Pharmacy;
Department of Internal Medicine, University of Utah; Jondi-Shapoor University of Medical
Sciences; Department of Psychiatry & Behavioral Sciences, Duke University Medical
Center; and Multiple Sclerosis Center at UCSF6. These efforts were pioneered by leading
immunologists Dr. Nicholas Plotnikoff, Dr. Ronald Herberman, Dr. Bernard Bihari, Dr.
Angus Dalgleish, Dr. Ian S. Zagon, Dr. Jill Smith, Dr. McLaughlin, Dr. Jacqueline
McCandless, and Moshe Rogosnitzky, among others.
HOW LDN WORKS
The mechanism of action of naltrexone, in autoimmune diseases and cancer, is still being
researched, but there are theories as to the mechanism of action that both explain why
LDN works on both autoimmune diseases and cancers, as well as inflammatory disease.
According to Mark J. Donahue’s paper on LDN that uses interviews from Dr. David,
Gluck, Dr. Jacquelyn McCandless, Dr. Jarred Younger, and Dr. Ian Zagon:
“LDN is an opioid antagonist that not only blocks the reception of opiates, but also the
body’s own endogenous opioids – endorphins. However, because LDN is administered in
such a 'low dose' it is believed that LDN only briefly (for 3-4 hours) obstructs the effects
of endorphins. Sensing an endorphin deficit, the hypothalamus signals for increased
production of endorphins in what is called 'the rebound effect.' The rebound effect results
in three things happening:
- Opioid receptor production increases in order to try and capture more endorphins.
- Opioid receptor sensitivity increases, also in order to try and capture more endorphins.
- Production of endorphins is increased in order to compensate for the perceive shortage.
Once LDN is metabolized by the liver and eliminated from the body (after 3-4 hours), the
elevated levels of endorphins produced, as a result of the rebound effect, can now
interact and bind with the more sensitive and more plentiful opioid receptors. These
opioid receptors, are found throughout the body, including virtually every cell of the
body’s immune system.
The elevated levels of endorphins will usually last around 18-20 hours. During this time
the elevated endorphins act by up-regulating vital elements of the body’s immune cells.
By doing so clinical trials has been shown that elevated levels of
- Down regulating inflammatory cytokines
- Reducing inflammation and oxidative stress
- Facilitating tissue repair and wound healing
- Restoring T-helper/CD4 levels
- Restoring the balance between Th1 & Th2 lymphocytes
- Increasing cytotoxic T cells and natural killer (NK) cells
- Regulating cell growth & inhibiting tumor growth
- Reducing excitotoxicity and microglial activation
- Reducing apoptosis of the myelin-producing oligodendrocytes
- Stimulating mucosal healing (lining of bowel)”7
According to Dr. Nancy Sajben in an article she wrote about LDN, she explains it’s
mechanism as follows:
“In 2008 in the US and UK have shown that naltrexone in addition to binding to the
opiate receptor’s binds to naltrexone in addition to binding to the opiate receptor’s binds
to Toll Like Receptors (TLR),. There are 13 TLRs, and so far they have studied naltrexone
only in two of them TRL4 and TRL9. That is important because the TLR receptors are
part of the innate immune system and effect the inflammatory markers.
The Toll Like Receptors are not like other receptors. They are not these snug little
pockets where naltrexone binds. Instead the Toll Like Receptors are like an entire
football field, with enormous nooks and crannies where it has many interactions with
many molecules. Now, in 2010, scientists are asking if naloxone or naltrexone is acting
at TLR4 or even higher up in the cascade.
The study of immune cell glial interactions is in its infancy. Glial cells are the immune
cells in your central nervous system (brain, spinal cord). They are very involved in
dysregulation of pain systems, neuroinflammation, and some neurological diseases such
as Multiple Sclerosis, Alzheimer’s, Parkinson ’s disease, Autism, ALS, infections of the
brain, etc.” 8