Low-Dose Naltrexone

Low Dose Naltrexone is my “golden nugget.” It’s not a magic bullet … but we’re getting dangerously close. It’s simple, cheap, safe—it’s the hero I repeatedly need to put out the fire behind so many chronic issues.

After 25 years in practice, I’ve learned that most chronic conditions—CIRS, Lyme, Long COVID, POTS—all share a common source: your immune system gone haywire. In a word…inflammation. And Low Dose Naltrexone has become my go-to solution for resetting the entire system.

But we should back up. What is naltrexone, and why is “low dose” so important?

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Every Hero Has an Origin Story

The Accidental Discovery That Changed Everything

The story of Low Dose Naltrexone starts with an accidental discovery back in 1985. Dr. Bernard Bihari was a New York doctor treating heroin addicts during the AIDS epidemic when he noticed something weird: patients taking tiny doses of naltrexone—just 3mg instead of the usual 50mg—had much better immune function¹.

This got Dr. Bihari thinking: what if using just a tenth of the normal dose could do the opposite?

Instead of blocking endorphins completely like the 50mg dose, these tiny amounts only blocked the receptors for 4–6 hours. This triggers a surge in the body’s natural endorphin production lasting 18–24 hours.

Over the next few decades, the research kept piling up². But let me tell you about a couple of my patients instead.

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Real Patient Stories from My Practice

Lizzy’s Transformation

When Lizzy first walked into my office, she was 15 and struggling with what everyone thought was pandemic anxiety. Like many teenagers, going back to school after COVID lockdowns made her anxious. But this was different—she was lightheaded, dizzy, and nauseous constantly, like she might pass out.

What bothered me about Lizzy’s case was how the medical system had failed her. Doctor after doctor dismissed her symptoms. “It’s just anxiety. It’s all in your head.” They threw medications at her that made everything worse.

When Lizzy’s mom brought her to me—I was their last resort—I spent the first 30 minutes just listening. Then I did something simple that no other doctor had bothered with: a basic tilt table test.

I had Lizzy lie down and checked her blood pressure and pulse. Then sit up—checked again. Her heart rate jumped 15 beats per minute. Finally, I had her stand up and lean against the wall.

I lost her pulse. Her symptoms spiked. Blood pressure dropped below 90. Heart rate shot to 140. When I asked how she felt, she was getting dizzy and panicking. “My anxiety is getting really bad.”

But this wasn’t anxiety—it was POTS (Postural Orthostatic Tachycardia Syndrome). Every other doctor had missed it.

Once we had the right diagnosis, we put together a plan: dietary changes to stabilize blood sugar, more fluids and electrolytes, compression stockings, and specific exercises to retrain her nervous system. I also prescribed low-dose naltrexone, knowing from research that it could reduce the brain inflammation we see with POTS.

The improvement was steady. Within weeks, Lizzy’s “anxiety” started getting better. Within months, she was back to normal teenage life—school, activities, everything. The change was so dramatic that her old doctors could barely believe it was the same kid.

Sarah’s Journey From Chronic Fatigue to Pregnancy

Sarah came to me with that thick folder of medical records I see too often—years of searching for answers that regular doctors couldn’t give her.

At thirty-five, Sarah had done everything “right”—eating well, exercising regularly, getting check-ups. But her health had fallen apart anyway. Crushing fatigue, brain fog so thick she could barely think, and body aches that made every day miserable. Her doctors ran tests, gave her medications. Nothing helped.

The medical system had gaslit her too. Some doctors said depression. Others said chronic fatigue syndrome. One actually told her it was just “part of being a busy, stressed professional.”

In one comprehensive visit with Sarah, I found what everyone else had missed:

• Hidden thyroid problems with positive thyroid antibodies—Hashimoto’s thyroiditis, an autoimmune condition no other doctor had bothered to test for.
• Environmental toxicity from mold in her home. Testing showed mycotoxins in her system, and we found significant mold growth where she spent most of her time.
• Gut problems including SIBO and CIRS, both caused by mold exposure. Her gut—where most serotonin is made—was a mess, explaining both physical and mood symptoms.
• Multiple nutritional deficiencies, including B vitamins, magnesium, and omega-3s—all crucial for energy and brain function.

Sarah’s treatment included low-dose naltrexone to help balance her immune system and reduce chronic inflammation from mold exposure. She and her husband moved out of the moldy house, started detox protocols, healed her gut, fixed nutritional deficiencies, and got her thyroid working properly.

The improvement was gradual but steady. Within three months, Sarah’s energy started returning. By six months, she felt better than she had in years. But the best part happened a year later—after several heartbreaking miscarriages and being told she had fertility problems, Sarah got pregnant.

We didn’t just treat symptoms—we addressed the autoimmune problem itself. By healing her gut, replacing missing nutrients, and removing environmental toxins while using LDN to balance her immune system, we stopped her undiagnosed autoimmune condition from progressing.

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How Low Dose Naltrexone Actually Works

For patients who want natural healing, Low Dose Naltrexone actually boosts your body’s own pharmacy instead of adding foreign chemicals³. This matters for understanding why LDN fits with functional medicine:

• NSAIDs suppress inflammation … LDN regulates immune balance
• Steroids shut down immunity … LDN optimizes immune function
• Immunosuppressants weaken defenses … LDN modulates responses appropriately

The temporary receptor blockade triggers your body to naturally make more endorphins—training your healing systems to work better⁴. This works with your body’s natural healing instead of fighting against it.

The Goldilocks Principle: Why 4.5mg is “Just Right”

At 4.5mg, LDN creates what researchers call intermittent receptor blockade⁵. Think of it like this: if you cover a garden sprinkler for a few hours, when you uncover it, all that built-up pressure makes it spray harder for the next 18–24 hours.

This 4–6 hour blockade tricks your body into thinking it’s not making enough endorphins⁶. So your body compensates by:

• Producing 300% more beta-endorphins (your body’s natural painkillers)⁷
• Creating additional endorphin receptors
• Making existing receptors more sensitive to endorphins

Beta-endorphins are actually stronger than morphine for pain relief—Low Dose Naltrexone just helps your body make more naturally, without side effects or addiction risks.⁸

Resetting Your Body’s Thermostat

When I explain LDN to patients with chronic inflammation, I tell them it’s like resetting a broken thermostat⁹. In chronic illness, your body’s inflammatory thermostat gets stuck on “high,” constantly calling for inflammation even when you don’t need it.

Low Dose Naltrexone fixes this by:

• Calming overactive microglia—the brain’s cleanup crew that’s gotten too aggressive
• Rebalancing the TH1/TH2 immune response—like fixing a seesaw that’s stuck tilted to one side
• Boosting T-regulatory cells—your immune system’s peacekeepers

Unlike immunosuppressive drugs that weaken your whole immune system, or NSAIDs that just block inflammation temporarily, LDN teaches your immune system how to work properly again¹⁰. It brings back natural balance instead of shutting everything down.

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Where I’ve Seen Miracles (And Where I Haven’t)

Long COVID: My Most Consistent Successes

In my practice, Long COVID responds better than anything else to LDN therapy. A Veterans Affairs study found that patients were over 5 times more likely to get better compared to physical therapy alone¹¹. In a 12-week study combining LDN with NAD+, quality of life scores went from 36.5 to 52.1, while fatigue scores dropped significantly¹².

What I see in my practice matches the research: 60–80% of Long COVID patients get real improvement, especially with:

• Less fatigue and more energy
• Clearer thinking and better brain function
• Less post-exertional malaise (the crash after activity)
• Better sleep and mood stability

Most patients start feeling better within 2–3 weeks, though I tell everyone the full benefits usually show up after 2–3 months.

POTS … More Complex

For patients like Lizzy with POTS, the results are more mixed. It’s important to remember there are three main types of POTS: autoimmune, neurogenic, and adrenergic.

The research suggests LDN helps a specific group—those where autoimmune inflammation is the problem¹³. Also, POTS patients often need lower doses (2.5–3mg instead of the usual 4.5mg) and slower dose increases because their nervous systems are more sensitive.

CIRS & Mold Illness: Part of a Bigger Picture

For patients with Chronic Inflammatory Response Syndrome—often from mold exposure like Sarah had—Low Dose Naltrexone is one piece of comprehensive treatment. I usually add LDN to established protocols like Shoemaker’s approach after initial toxin removal and binding phases.

Patient surveys show that among those who tried LDN for CIRS, most said it was “critically important or very helpful”¹⁴. The anti-inflammatory effects help reduce chronic inflammation from biotoxin exposure while balancing the immune system.

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Practical Stuff

Safety: Why I’m Comfortable Prescribing LDN

Compared to conventional anti-inflammatory medications, Low Dose Naltrexone has a much better safety profile¹⁵. While NSAIDs can cause stomach bleeding, kidney damage, and heart problems, LDN’s side effects are minimal and usually temporary:

• Most common: Vivid dreams (usually go away within 2–4 weeks)
• Sometimes: Mild headaches or sleep problems at first
• Rare: Mild nausea or fatigue when you first start

Unlike immunosuppressants, LDN doesn’t increase infection risk or hurt your body’s ability to fight cancer¹⁶. Over 30 years of use shows no serious long-term safety issues.

Cost

Monthly costs average $35–70 for compounded LDN—cheaper than many conventional medications my patients were taking before. Insurance rarely covers off-label compounded medications, but cash prices are often less than insurance copays anyway.

I help patients save by shopping around (prices vary significantly), ordering 90-day supplies for better pricing, and using reputable mail-order pharmacies.

Why Quality Compounding Matters

Since the FDA only approves 50mg tablets for addiction treatment, Low Dose Naltrexone needs compounding to get treatment doses of 1.5–4.5mg¹⁷. This isn’t a limitation—it allows precise, individualized dosing.

I only work with PCAB-accredited compounding pharmacies for consistency and purity. Immediate-release formulations are essential—extended-release versions block the crucial rebound effect¹⁸.

I usually recommend specialized mail-order pharmacies like Care First Specialty Pharmacy and Avrio Pharmacy. I make sure patients get formulations without calcium, gluten, lactose, and artificial dyes.

Dosing Strategy

Most patients need 2–3 months to accurately assess LDN effectiveness, though some notice improvements within weeks. I start low and increase gradually:

Standard Protocol:

• Week 1: 1.5mg daily (at bedtime)
• Week 2: Increase to 3mg daily
• Week 3+: Maintain at 4.5mg daily (the optimal dose for most conditions)

Sensitive Patient Protocol:

• Start at 0.5mg with weekly increases of 0.5mg
• Stay at each dose level for 2 weeks
• Stop increasing when you get the best response instead of automatically going to 4.5mg

Special Considerations:

• POTS patients often do best at 2.5–3mg
• Long COVID patients usually follow standard escalation to 4.5mg
• CIRS patients may need even slower increases to avoid detox reactions
• Always take at least 2–4 hours after any binding agents or medications

Most patients take LDN at bedtime, though those getting vivid dreams can switch to morning without losing effectiveness. Dreams usually resolve within 2–4 weeks.

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How LDN Works with Natural Healing

One of the reasons I like Low Dose Naltrexone is how well it works with natural anti-inflammatory approaches¹⁹:

• Omega-3 fatty acids and curcumin provide systemic anti-inflammatory effects while LDN handles brain and nervous system inflammation.
• Adaptogenic herbs help with stress response while LDN provides immune optimization. I often combine LDN with IV therapies including glutathione and vitamin C.

Key principle: add supplements gradually over months to identify individual responses. Never overwhelm patients with too many changes at once.

Exercise & Movement

Exercise and Low Dose Naltrexone both increase endorphins through different pathways, creating powerful synergy²⁰. Many of my patients report improved exercise tolerance and recovery, with fibromyalgia patients better able to tolerate movement that was previously impossible due to pain.

This creates a positive feedback loop I love seeing: LDN reduces baseline inflammation, making movement more comfortable. Regular movement then provides additional anti-inflammatory benefits, supporting LDN’s effectiveness.

Sleep & Stress

Low Dose Naltrexone helps normalize your body’s stress response system by reducing inflammatory cytokines²¹. When I combine LDN with stress reduction techniques like meditation or breathwork, LDN provides the biochemical foundation while these practices provide the behavioral tools.

Quality sleep is when your body performs its most critical healing processes. LDN can significantly improve sleep quality by reducing pain and inflammation that interfere with restorative sleep cycles—creating another positive feedback loop where better sleep supports LDN’s effectiveness.

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My Playbook for LDN Success

Through years of practice, I’ve found Low Dose Naltrexone shows particular promise for patients with²²:

• Autoimmune conditions (rheumatoid arthritis, multiple sclerosis, Crohn’s disease, Hashimoto’s)
• Chronic pain syndromes (fibromyalgia, chronic fatigue syndrome)
• Post-viral conditions (Long COVID, post-viral fatigue)
• Complex chronic illness not responding to conventional approaches

These are the patients I see most in functional medicine—people the conventional system has failed or dismissed.

Contraindications

Absolute contraindications I never compromise on:

• Current opioid medication use (LDN will block their effectiveness)
• Severe liver disease
• Pregnancy and breastfeeding (insufficient safety data)

Relative contraindications requiring careful consideration:

• Organ transplant recipients taking immunosuppressive medications
• Active cancer treatment

How I Monitor Success

Success with Low Dose Naltrexone encompasses both measurable improvements and patient-reported changes:

What I track: Reduced inflammatory markers (ESR, CRP), improved functional scores, decreased need for pain medications.

What patients report: Reduced pain levels, increased energy, enhanced mood stability, better cognitive function, improved exercise tolerance.

My typical timeline spans 12 months: initial response assessment (months 1–3), protocol optimization (months 4–6), and long-term maintenance (months 7–12)²³. I always maintain clear communication about the 2–3 month assessment period needed before determining full efficacy.

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The Future of LDN (My Practice & Beyond)

After using Low Dose Naltrexone in my practice for several years now, I can confidently say it’s something unique in modern medicine—a drug that actually supports your body’s natural healing instead of fighting against it. Sometimes, the most powerful medicine just helps your body remember how to heal itself.

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Ready to explore whether Low Dose Naltrexone could be part of your healing journey? If you’re a member at RIFM and struggling with inflammation, talk to your provider about whether LDN might complement your existing protocol.

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References

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