The Three Roles of Low Dose Naltrexone in Dr. Kim’s Practice

By Yoon Hang Kim, MD, MPH, FAAMA

When a patient asked me to look into Low Dose Naltrexone for her autoimmune condition back in 2015, I had no idea that moment would reshape the way I practice medicine.

What I found was a medication with a remarkable safety profile, an almost unbelievable cost — often less than a dollar a day — and a growing body of evidence suggesting it could help conditions ranging from autoimmune disease to chronic pain to cancer. I prescribed it. She went into remission. And I’ve been studying, prescribing, and refining my approach to LDN ever since.

Over the past decade, I’ve had the opportunity to use LDN across a wide range of clinical settings — at Miami Cancer Institute, the University of Kansas, WellMed/Optum, Memorial Hospital, and now at Hill Country Integrative Medicine in Fredericksburg, Texas. Through thousands of patient encounters, I’ve come to understand that LDN doesn’t do just one thing. It works through at least three distinct but interconnected roles, and understanding these roles is key to using it well.

Role 1: Immune Modulation

This is where most people first encounter LDN — and where I first encountered it myself. LDN has the ability to modulate the immune system, and that single property makes it relevant to an enormous range of conditions: autoimmune diseases, cancer, and what I’ve come to call immune derangement syndrome.

Autoimmune Disease. The science here goes back decades. Research as early as 1986 showed that naltrexone enhanced immune function by increasing natural killer cell activity. By 1999, animal studies demonstrated that autoimmune diseases like lupus and autoimmune thyroiditis were preceded by endorphin deficiencies in the brain — suggesting that endorphin depletion might actually predispose someone to autoimmune illness. In 2005, researchers confirmed that endorphins reduce inflammatory and autoimmune factors and show promise as anti-inflammatory agents.

What does this mean practically? LDN briefly blocks opioid receptors, which triggers the body to produce more endorphins and enkephalins. Those endorphins then regulate the immune system — calming overactivity without suppressing the immune system the way steroids or conventional immunosuppressants do. I’ve seen this play out in my own practice with conditions like Hashimoto’s thyroiditis, rheumatoid arthritis, lupus, multiple sclerosis, and Crohn’s disease. In many cases, patients experience significant improvement, and some achieve full remission.

Cancer. The immune modulation story extends directly into oncology. If LDN enhances natural killer cell activity, that has obvious implications for cancer surveillance and treatment. Dr. Burt Berkson’s pioneering work with LDN and alpha-lipoic acid in pancreatic cancer showed remarkable survival outcomes. In my own integrative oncology practice — from Miami Cancer Institute to Hill Country — I’ve incorporated LDN as part of comprehensive cancer protocols that also include metabolic strategies, targeted supplementation, and conventional treatment when appropriate.

I want to be clear: LDN is not a cancer cure. But as an adjunctive therapy that strengthens immune function, it’s a tool I reach for consistently. Cancer patients who receive LDN alongside other integrative therapies often show improved quality of life, and in some cases, outcomes that exceed expectations.

Immune Derangement Syndrome. This is a concept I’ve developed over years of seeing patients whose immune systems aren’t just overactive or underactive — they’re dysregulated. Conditions like Mast Cell Activation Syndrome (MCAS), Long COVID, and chronic inflammatory response syndrome don’t fit neatly into the autoimmune box. The immune system isn’t attacking self-tissue in the classic sense. It’s deranged — firing inappropriately, reacting to triggers it shouldn’t, and creating a cascade of symptoms that can affect every organ system.

LDN plays a critical role in these cases, but it’s often necessary rather than sufficient on its own. For complex immune derangement, I frequently combine LDN with mast cell stabilizers like ketotifen and cromolyn sodium, metabolic support through ketosis, and sometimes methylene blue for mitochondrial function. LDN calms the immune system enough to make deeper treatment more successful and better tolerated. It creates a foundation on which other therapies can work.

Role 2: Anti-Neuroinflammatory Agent

This is where the science gets particularly fascinating, and where I think LDN is most underappreciated.

Beyond its effects on endorphins, LDN has a direct anti-inflammatory action in the central nervous system. It works through a mechanism that’s entirely separate from the endorphin pathway: the blockade of Toll-like receptor 4, or TLR4.

Here’s why that matters. Your brain has its own immune cells called microglia. Think of them as the macrophages of the central nervous system. Under normal conditions, they lie dormant. But when they become activated — by injury, infection, chronic stress, or systemic inflammation — they release pro-inflammatory cytokines that contribute to pain, fatigue, brain fog, depression, and a host of neurological symptoms.

LDN, through TLR4 blockade, prevents the overactivation of these microglial cells. It calms the neuroinflammatory fire. This is distinct from the endorphin effect, which means LDN is working through two separate anti-inflammatory pathways simultaneously.

In my practice, this dual mechanism explains why LDN is effective across such a wide range of conditions. Patients with fibromyalgia, chronic fatigue, migraines, and chronic pain often have significant neuroinflammatory components driving their symptoms. Clinical trials have shown that fibromyalgia patients treated with LDN experienced meaningful reductions in baseline pain, along with improved mood and quality of life. I’ve seen patients with chronic migraines experience both prevention and relief of attacks through LDN’s modulation of central nervous system inflammation.

Even conditions you might not immediately associate with neuroinflammation — like insomnia and tinnitus — can respond to LDN. I’ve had patients whose sleep normalized and whose tinnitus decreased significantly, and in some cases, the improvements persisted even after discontinuing LDN. That’s the behavior of a true adaptogen — a therapy that restores balance and then allows the body to maintain it.

Role 3: Neuroprotective and Neurotrophic Agent

This is the role of LDN that excites me most about the future, and the one that is perhaps least understood.

We are in the middle of a neurodegeneration crisis. Dementia is being diagnosed in people as young as their late 40s. Death rates from Alzheimer’s and Parkinson’s are climbing sharply. A study comparing 21 Western countries found that every country’s neurological deaths rose relative to controls, with the United States ranking near the top in both dementia risk and national stress levels. That correlation should not be ignored.

I believe chronic stress depletes endorphins, and that endorphin deficiency may be a predisposing factor in neurodegenerative conditions. Research supports this — studies have shown that animals with autoimmune diseases had significantly lower endorphin levels in the hypothalamus, and that these deficits preceded the onset of disease. If endorphin depletion can trigger autoimmune disease, it’s reasonable to ask whether it might also contribute to neurodegeneration.

LDN’s potential neuroprotective role works through several mechanisms. By increasing endorphin production and sensitizing the body’s opioid receptors, LDN may help build what I think of as a “stress-resistant brain.” Research has shown that exercise prevents learned helplessness partly through raising endorphin levels — and LDN raises endorphins through a complementary pathway. Additionally, LDN’s anti-neuroinflammatory action through TLR4 blockade may protect neurons from the chronic inflammatory damage that drives neurodegeneration.

The clinical evidence is still early, but what I’ve seen in practice is striking. I’ve had a dementia patient whose son reported almost immediate improvement in memory after starting LDN. I’ve had a Parkinson’s patient who was underweight, extremely weak, and dependent on a walker — after starting LDN, she gained weight, walked better, regained strength, and traveled internationally to visit her daughter. A patient with severe multiple sclerosis who was on the verge of needing a wheelchair achieved remission and now hikes mountains.

Are these anecdotes? Yes. Do they prove LDN is neuroprotective? Not in the way a randomized controlled trial would. But after two decades of clinical observation, I’ve seen enough to believe that LDN has a role to play not just in treating neurological disease, but potentially in preventing it. The combination of increased endorphin production, enhanced receptor sensitivity, and reduced neuroinflammation creates a neurological environment that favors resilience and repair.

One Medication, Three Roles, One Philosophy

What makes LDN unique in my practice is that these three roles aren’t separate — they’re interconnected. Immune modulation reduces the systemic inflammation that drives neuroinflammation. Reduced neuroinflammation protects the brain. A protected, well-functioning brain better regulates the immune system. It’s a virtuous cycle, and LDN sits at the hub of it.

But I want to be honest about what LDN is and isn’t. Published literature shows response rates typically ranging from 57–65% in chronic pain populations. In my clinical experience, patients fall into three categories: those for whom LDN alone is sufficient, those for whom LDN is necessary but not sufficient (requiring additional therapies), and non-responders. About a third of patients may not respond to any given therapy, and LDN is no exception.

What I can tell you is that for the right patient, at the right dose, with the right supporting strategies, LDN is one of the most valuable tools in integrative medicine. It’s safe, it’s affordable, and it works through the body’s own healing mechanisms rather than against them.

Because at the end of the day, it’s never about the medication. It’s about the patient