Low-Dose Naltrexone: A Promising, Low-Cost, Low-Side-Effect Option for Fibromyalgia Pain
If you’ve lived with fibromyalgia for any length of time, you’ve probably tried a long list of medications—some that helped, some that didn’t, and some that brought relief but came with side effects you couldn’t tolerate.
There is one medication, however, that has been quietly gaining attention in the fibromyalgia community and among researchers: low-dose naltrexone (LDN). (Moser U., 2025).
Originally created to help people recovering from opioid or alcohol dependence, naltrexone—when taken in very small doses—appears to have a completely different effect:
✧ Less inflammation
✧ Reduced pain
✧ Improved energy
✧ Better sleep
Let’s walk through what the research says, how LDN works, and why a brand-new clinical trial is taking this medication seriously for fibromyalgia.
What Exactly Is Low-Dose Naltrexone?
In its standard form (50 mg), naltrexone blocks opioid receptors and is used to help prevent relapse in people recovering from substance use. However, when taken at very low doses—typically 1–6 mg—it seems to do something entirely different.
Researchers call this “paradoxical”:
The same medication that blocks endorphins at high doses may boost the body’s natural pain-relieving system at low doses.
This tiny dose appears to gently nudge the nervous system, immune system, and inflammatory pathways in ways that may be beneficial for fibromyalgia.
How Does LDN Work? Two Key Mechanisms
Although research is still growing, two main biological pathways help explain why LDN may help people with fibromyalgia.
1. Boosting the Body’s Own Endorphins
LDN temporarily blocks opioid receptors for a few hours, and the body responds by making more opioid receptors and more endorphins (your natural painkillers).
It’s like your body says:
“Hey! I need more pain relief!”
…and ramps up its own internal pharmacy.
This effect may increase:
Natural pain relief
Emotional resilience
Stress tolerance
For people with fibromyalgia—whose pain-processing systems are often under intense strain—this can make a real difference.
2. Calming Overactive Immune Cells in the Nervous System
Fibromyalgia is increasingly understood as a condition involving neuroinflammation—not damage, but an over-activated alarm system within the nervous system.
LDN appears to calm this response by blocking TLR4 receptors on two types of immune cells in the brain and spinal cord:
Microglia
Astrocytes
When these cells become overactive, they release inflammatory chemicals that can worsen:
Widespread pain
Fatigue
Brain fog
Sensitivity to touch or stress
LDN helps quiet this inflammatory cascade, which may reduce pain amplification.
This is why researchers are excited:
LDN doesn’t just mask symptoms—it may remodel the system that drives them.
What Does the Research Show So Far?
While LDN has been used informally for years, official studies are still catching up. Here’s what we know from published research:
Study #1: Improved Pain Thresholds
A small pilot study with 10 women found that LDN (4.5 mg) improved tolerance to pressure and heat pain. Participants reported noticeable symptom relief.
Study #2: Double-Blind, Placebo-Controlled Trial
A more rigorous study with 31 women found that LDN significantly reduced pain compared to placebo. This is the strongest evidence so far.
Participants took:
12 weeks of LDN 4.5 mg
Or 12 weeks of placebo (in a crossover design)
Results:
✓ Less pain
✓ Better daily functioning
✓ Some improvements in mood and energy
Study #3: Anti-Inflammatory Effects Confirmed
A newer pilot study measured cytokines (inflammatory signals) in women with fibromyalgia.
LDN led to reductions in 17 different pro-inflammatory cytokines.
This supports the idea that LDN reduces neuroinflammation.
Safety Profile
Across studies, LDN is consistently described as:
Very safe
Low-cost
Generally free of major side effects
Most common side effects: vivid dreams, mild insomnia, and occasional headaches (usually temporary)
The New Study: Testing a Higher Dose (6 mg)
Building on earlier studies that used 4.5 mg and showed promise, researchers in Denmark are now conducting a large, high-quality clinical trial to investigate whether 6 mg might be even more effective.
Here’s what makes this study exciting:
✔ 100 women with fibromyalgia
A much larger sample than previous studies.
✔ 12 weeks, placebo-controlled, double-blind
The gold standard in medical research.
✔ Gradual titration from 1.5 mg → 6 mg
To maximize tolerability.
✔ Measures not just pain but also:
Fatigue
Sleep quality
Physical function
Tenderness
Mood
Cognitive symptoms
Blood markers of inflammation
Measures of pain processing (e.g., pain thresholds, modulation)
Why 6 mg?
A prior dose-response study found:
ED50 (helpful for half of patients): 3.88 mg
ED95 (helpful for 95% of patients): 5.40 mg
Meaning:
Most people might do slightly better above the traditional 4.5 mg dose.
Thus, 6 mg is being tested.
So… Should You Consider LDN?
Here’s the balanced, heart-centered FibroSoul take:
LDN may be worth discussing with your provider if you:
Struggle with widespread pain
React poorly to conventional fibro medications
Want a low-risk, affordable option
Curious about immune and neuroinflammation-based treatments
LDN may not be right if you:
Are currently taking opioid medications (they cannot be mixed)
Are pregnant or breastfeeding
Have liver issues or certain medical conditions
The upside?
LDN is one of the most promising “emerging” treatments for fibromyalgia—and one of the gentlest.
The downside?
Research is still evolving, and not all doctors are familiar with LDN. It may require finding a knowledgeable prescriber or a compounding pharmacy.
The Soulful Bottom Line
Here at FibroSoul, we hold a simple belief:
Your body is not broken—it’s communicating.
LDN is one of the treatments that seems to honor this principle. Rather than overpowering your system, it appears to support your body’s natural balance:
Supporting your endorphins
Calming overactive immune responses
Quieting the nervous system
Reducing inflammation
Gently restoring harmony
LDN isn’t a miracle cure, but for many people, it is a meaningful piece of their healing puzzle.
And as large, carefully designed trials move forward, we’re finally getting the high-quality data needed to understand its true potential.
Fibromyalgia research is turning a corner, and medications like LDN are part of that new, hopeful landscape.