What Is LDN and Why Don't More Doctors Know About It?

By Dr. Matt Altman, MD | Rooted Health Clinic, Salado, Texas

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About a quarter of the patients I see end up on low dose naltrexone. And almost every one of them had never heard of it before walking into my office. They'd seen specialists, tried steroids, biologics, antidepressants, pain medications — and nobody mentioned a $30-a-month compounded medication that's been studied for decades.

To understand why I use LDN so often, you have to understand how I think about patients in the first place.

How I Approach Every Patient

When someone walks into my clinic, I'm not just looking at their chief complaint. I'm looking at the whole picture through what I call a tiered framework.

Tier one is always gut health, metabolic health, and your stress response system. This is the foundation. If your gut is a mess, if your blood sugar and insulin are out of whack, if your thyroid isn't functioning well — nothing else is going to work right until we address those things first. You can't build a house on a broken foundation.

Once that foundation is solid — or at least moving in the right direction — tier two looks deeper. Environmental exposures, toxins, food sensitivities, hormones. There's some overlap between tiers, and that's intentional. Hormones can show up in tier one or two depending on the situation. Food sensitivities might be part of the gut picture or their own separate issue.

Tier three is where we get into genetics, structural problems, and the more complex stuff that requires everything else to be addressed first.

Now here's the thing that most functional medicine practitioners miss. A lot of patients who come to me are so functionally depleted — so exhausted, so much pain, so depressed — that they don't have the realistic capacity to jump into a ketogenic diet or overhaul their sleep habits or start a new supplement regimen. They just don't have the bandwidth. So sometimes we have to jump above what I call the pillars of health — sleep, diet, exercise, environment, community, mental health — and intervene medically first, just to get the patient functional enough to then make those lifestyle changes.

It's not a straight line. You meet people where they are. And that's exactly where medications like ivermectin and LDN come in.

Starting With Ivermectin

When a patient comes in with chronic fatigue, chronic Epstein-Barr virus, or Long COVID, my very first line treatment is actually ivermectin — not LDN.

Most people only heard about ivermectin during COVID, and unfortunately the conversation got so politicized that the actual science got buried. But ivermectin has well-documented broad-spectrum antiviral properties. It works by blocking a protein called importin alpha that viruses use to hijack your cells' machinery. Research published in the Journal of Antibiotics showed antiviral activity against multiple RNA and DNA viruses, including herpesviruses — which is the family Epstein-Barr belongs to.

For Long COVID specifically, I've seen it help patients who were stuck in that post-viral fatigue state where they crash after any exertion, their brain fog won't clear, and they feel like they've aged twenty years overnight. The mechanism makes sense — if there's ongoing viral persistence or reactivation driving chronic immune activation, an antiviral approach addresses the root cause rather than just managing symptoms.

I mention ivermectin here because it sets up why LDN is so valuable. These two medications work through completely different pathways, and together they cover both sides of the problem: the viral trigger and the immune dysregulation it causes.

How LDN Actually Works

Naltrexone at full dose — 50mg — is used in addiction medicine. It blocks opioid receptors completely. Low dose naltrexone is a completely different story. We're talking 1.5 to 4.5mg, about a tenth of the standard dose.

At that low dose, naltrexone creates a brief blockade of your opioid receptors while you're sleeping — usually four to six hours. Your body notices and compensates by ramping up its own endorphin production. So when the medication wears off, you're left with higher levels of your body's natural pain-relief and immune-regulation molecules.

But the endorphin piece is only part of it. LDN also directly calms down overactive immune signaling. In conditions like chronic fatigue or autoimmunity, your immune system's alarm switches get stuck in the "on" position. That's what drives the brain fog, the joint pain, the crushing fatigue — your immune system constantly firing when it shouldn't be. LDN helps shift the immune system away from that hyperactive state and back toward balance.

This is why it pairs so well with ivermectin. Ivermectin goes after the viral trigger. LDN calms down the immune system that's been thrown into overdrive by that trigger. You're addressing the problem from both ends.

The Research Behind LDN for Fatigue and Post-Viral Illness

This isn't just clinical observation. There's real research backing this up.

A 2024 study published in Brain, Behavior, and Immunity found that LDN combined with NAD+ significantly improved fatigue scores in patients with persistent post-COVID symptoms. A 2025 systematic review in the journal COVID analyzed multiple studies and concluded that LDN shows promise as a therapeutic option for Long COVID, specifically citing improvements in fatigue, pain, and cognitive function.

For chronic fatigue syndrome specifically, researchers have found that LDN restores function in specific ion channels on natural killer cells — the immune cells responsible for fighting viral infections — that are dysfunctional in ME/CFS patients. A 2025 study in Frontiers in Molecular Biosciences demonstrated this restoration at the cellular level, which helps explain why patients feel tangibly better.

A BMJ case report from 2020 documented significant improvement in a chronic fatigue patient on LDN, and a clinical practice review published in Fatigue: Biomedicine, Health & Behavior reported both safety and effectiveness data supporting LDN at 3 to 4.5mg daily for ME/CFS.

Beyond Fatigue — Where Else LDN Helps

The immune-modulating effects extend naturally into autoimmune conditions. Hashimoto's, rheumatoid arthritis, Crohn's disease, MS, lupus — if your immune system is attacking your own tissues and LDN helps bring that response back into balance, you'd expect improvement. Research in the American Journal of Gastroenterology confirms meaningful improvement in Crohn's patients, and multiple studies show quality of life benefits in MS.

Fibromyalgia and chronic pain respond because the pain in these conditions comes from neuroinflammation, not tissue damage. A Stanford study showed LDN reduced fibromyalgia pain by over 30% compared to placebo. I've had patients on gabapentin, tramadol, and muscle relaxers who got better results from LDN alone.

And mood consistently improves. When your immune system calms down and your endorphin levels come up, patients report less anxiety, better emotional resilience, more energy. It's not a separate effect — it's all connected back to that same immune and endorphin system.

Why Your Doctor Hasn't Mentioned It

The honest answer is three things, and they feed into each other.

There's no money in it. LDN is generic, compounded for about $30 a month. Nobody's funding the massive trials needed for an FDA indication because nobody profits from it.

That means it's not in the guidelines. Most doctors follow the algorithm on their screen. No big trial, no guideline inclusion, no prescription.

And doctors weren't trained on it. I wasn't either. I learned about it from the research and from seeing results in my own patients. Most physicians don't have the bandwidth to dig into off-label compounded medications that nobody's marketing to them.

How I Use It in Practice

I start at 1.5mg at bedtime and titrate up to 4.5mg over four to six weeks. Going slow matters because some patients get vivid dreams or mild sleep disruption early on. That usually resolves in a week or two.

The key thing — LDN is never the whole plan. It fits into that tiered framework. If someone comes in with chronic fatigue, I'm also looking at their gut health, their cortisol patterns, their nutrient status, their toxic exposures. LDN addresses the immune piece, but you still have to find what's driving the dysfunction in the first place. And sometimes you have to use it early — before the patient has the energy to make bigger lifestyle changes — just to get them functional enough to do the deeper work.

Side effects are essentially nothing. Vivid dreams, maybe a mild headache the first week. Compare that to biologics at $6,000 a month with lymphoma warnings, and the risk-benefit calculation isn't even close.

About two-thirds of my patients notice real improvement within four to eight weeks. That's a high response rate for any single intervention.

The Bottom Line

If you're dealing with chronic fatigue, Long COVID, chronic Epstein-Barr, autoimmune issues, or persistent pain that nobody can explain — and what you're currently doing isn't working — LDN deserves a real conversation with a doctor who understands it.

I see patients every week who've been through the conventional medicine gauntlet and nobody tried something this straightforward. That's not a failure of the medication. That's a system that hasn't kept up with the science.

At Rooted Health, we follow the evidence, not pharmaceutical marketing. And the evidence for LDN is too strong to keep ignoring.

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Dr. Matt Altman practices functional medicine at Rooted Health Clinic in Salado, Texas. To schedule an appointment, visit rootedhealthclinic.com or call 254-780-0023.