Low Dose Naltrexone (LDN): An Aide to Immune Repair and Restoration

In 1984 Naltrexone was approved by the FDA in the US for the treatment of opioid addiction, when used at doses of 50mg to 100mg per day. Acting as a pure opioid antagonist, naltrexone in higher doses blocks the effects of endogenous endorphins, that are seen in our own natural endorphins as well as those in drug abuse. Used in opioid overdose and opioid addiction, naltrexone suppresses the “high” experienced with drug use as well as helping minimize withdrawl symptoms in patients going through opioid recovery.

During the peak of the AIDS epidemic, researchers noted that when naltrexone was given in small doses to HIV/AIDS patients, T-cell levels improved! The increase in circulating T-cells helped regulate the immune system and thereby slowing down the disease progression.

It was this discovery that led to further research on understanding exactly how LDN, also known as low dose naltrexone, could be used in clinical practice as one of the greatest treatments for immune support and restoration.

Since LDN works on the deep cellular receptors, it proved difficult to find consistent ways to measure data and therefore not a lot is known on the EXACT mechanism by which LDN works. Due to the limited clinical trials, LDN could only be studied anecdotally by following the patient’s clinical response to treatment. Because of this, LDN never made it to main-stream medicine, until now.

Recent clinical research has shown that LDN, in doses of 0.5mg-4.5mg, although a pure opioid antagonist, does not appear to suppress the endorphins as seen in the higher dose, but in fact, has shown to stimulate the T-cells within our immune system.

According to LDNResearchTrust.org, LDN

• Causes increased endorphin release
• Increased endorphins that modulate the immune response
• Reduced the speed of unwanted cells growing. Dextro-Naltrexone is an antagonist for at least one, if not more immune cells
• Antagonizes “TLR,” suppressing cytokine modulated immune system
• Antagonizes TLR-mediated production of NF-kB – reducing inflammation, potentially downregulating oncogenes

Taking Naltrexone in larger doses of 50-300mg seems to negate the immunomodulatory effect by overwhelming the receptors, so for the effect to work, the dose must be in the range of 0.5-10mg, usually maxing at 4.5mg in clinical experience.

Since LDN will only block opioid receptors for three to five hours, the body experiences a rebound effect which greatly increases the production and utilization of endorphins. Once the LDN has fallen off the receptors and excreted, the increased number of endorphins bind to the now more-sensitive and more-plentiful receptors. As a result, these new and improved receptors assist in regulating cell growth, promoting healing, reducing inflammation, and increasing immunity and autophagy.

So what does this mean for you or me?

A few years ago, I began noticing that many of my patients were being treated with LDN for SIBO/Leaky Gut Syndrome by the Gastroenterologist. In the following months, Rheumatologists began prescribing it to help treat Auto-immune conditions.  What I observed was that when LDN was added to their other medications, overall severity of symptoms and relapse rates in health drastically reduced.  I was truly dumbfounded and confused as to how a medication in lower doses that was used to treat opioid addictions was life changing in autoimmune conditions.

I began my research into this potential “miracle” treatment. Given that LDN is not used in mainstream medical practice, it made me a bit leery to begin prescribing it, but it did not stop me from learning everything I could about it.

In March 2020, when the pandemic first began, I was so troubled to see young healthy individuals affected by the virus to a degree that you would not normally expect.  Why would they have this much of a hyper response of their immune system?

The great Dr. Fauci explained it so eloquently. When the virus enters the host (us), it triggers varying responses in our immune system to be able to fight off the virus. This is normal. This is what the body is supposed to do. Some systems may have a small inflammatory response, while others have a massive explosion of their cells.

Think of this analogy: a small fire (the virus) occurs while you are cooking.  Putting the fire out with a glass of water (normal immune response) would take care of it without causing any serious issues (mild symptoms). However,  if the pipes burst and flood the whole kitchen (severe Covid symptoms) in response to such a small fire, then we have bigger problems (ventilator, death, Covid long-hauler syndrome.)

In essence, the immune system is our built-in sprinkler system. It helps put out any fire that occurs in our bodies.

Exercising, adequate sleep, limiting processed foods, minimizing stress, avoiding excess alcohol etc. keep the fire from being created.

However, due to aging, genetics, poor health choices, medical conditions etc, the immune system finds it difficult to handle even small imbalances and begins to over-compensate the response by releasing excessive cytokines and other chemicals that cause a degree of inflammation that is out of proportion to the minor problem that occurred.

The over production of inflammatory components disrupts the natural defense mechanisms and begins signaling to attack our own cells. The body gets confused as to who is the good guy and who is the bad guy, so it attacks anything that comes in its way.  Hence the term AUTO immune.

The vicious cycle of inflammation-attack-inflammation-attack causes cells to mutate and develop into what we know as the disease state. This mutation further weakens our immune system which makes each cycle of inflammation worse than the one before.

So how do we stop this hamster wheel of destruction? That is the million-dollar question. No one has the definitive answer, but LDN has some promising scope.

Months into the pandemic, the science community began to develop some understanding of the nature of Covid’s behavior. However, my attention and worry turned to the potential long-term effects of the attack on our immune system, irrespective of the severity of the symptoms one experienced.

Have you ever wondered why everyone you know suddenly is affected by some form of autoimmune?

Much research is focusing on “Post Infectious Inflammation” as a potential cause of the rise in autoimmune conditions in the last decade.

Remember when you were a kid and were diagnosed with mono or were around your friends who had it?

One theory is that the Epstein-Barr virus, the virus that causes mono, triggered an initial immune response to the virus. Rather than clearing the body of the virus, the EBV remained dormant in the immune system. When there was an external (environmental or lifestyle choices) or internal trigger, it activated the immune system years after the initial infection. Once again, it was our immune mediated hyper-response that led to a decline in our T-cell function.  Similar findings were also discovered in post Ebola and SARS infections. This is the same pattern being seen in Covid long-hauler phenomena.

The decline in T-cell functioning is thought to be the epicenter of where disruption and breakdown of the body system begins affecting every organ and every disease process.

I am extremely terrified of what this virus could be doing to our immune systems 5-10-15 and even 20 years down the road.  The idea is not to live with the worry of ‘what ifs.’ But if we can understand other viruses’ response to our bodies, maybe we can do the same with Covid.

The symptoms we experience on a day to day basis – headache, weight gain, vision changes, joint pain, problems sleeping, GI issues, hormonal imbalances, and the list goes on and on, is thought to be a step from the exaggerated immune response.

Even as we identify the “cause” of those symptoms, why did the “cause” even happen? Let’s say you have been having weight gain and after blood work we identify the weight gain is coming from low thyroid. So we have an answer to the weight gain, but do we have an answer to why is the thyroid not optimally functioning?

That is how deep into the cells we need to go. LDN is helping us find and fix the cause for the causes at the root – where the real healing occurs –  in the immune system. That is where we need to go. We are not just going to the root. We are going to where the seed was first planted.

On January 28, 2021, a double-blinded placebo-controlled study testing LDN 4.5mg in Covid long haul patients began. The study is scheduled to finish August 2021 with preliminary results 12 weeks from the start of the study. Early indications look promising with patients reporting mild improvement in fatigue and muscle aches. That is a start!!

After seeing the results my patients were having with the LDN and after hours, months and even years of LDN research, I felt confidant to begin prescribing it to patients I felt could greatly benefit from the additional immune support.

Since LDN is not commercially available in the lower doses, it must be compounded at an accredited compounding pharmacy.

Doses can start as low as 0.25mg/day, as tolerated and titrated weekly as tolerated until reaching optimal dose of 4.5mg/day.

For some, the optimal dose may not be as high as 4.5mg/day. The body may respond at 1.5mg or 3.35mg. There is no perfect dose. As long as there is clinical improvement, the dose will remain effective for safe long-term use.

LDN is also used for many autoimmune conditions, MS, various cancers and a wide spectrum of other disease processes.

While LDN certainly does not replace the current standards of diagnosing and treating, nor do I believe this is the “one” pill to fix everything, I remain cautiously and excitedly optimistic.

While nothing can ever take the place of our bodies’ own power to heal, it is nice to know that there is something out there that can potentially help take healing beyond the root of the problem and into where the first break occurred.

There is hope!

Stay well. Stay healthy. Stay present. And remember, just breath.

It is all ok! We got this!