Hi Friend,
You have stabilised your Mast Cells. You have started "Emptying the Bucket." But for many in the MCAS-Fibro-ME/CFS Trifecta, a core problem remains: The brain is still hearing the noise.
When you have lived in a state of "Nervous System Overdrive" for years, the fire isn't just in your gut or your joints—it has moved into your Central Nervous System (CNS). This is why "standard" painkillers don't work. The problem isn't tissue damage; the problem is Central Sensitisation.
Today, we are doing a deep-dive into the "Heavy Hitter" of modern Neuro-Somatic medicine: Low Dose Naltrexone (LDN).
1. The History: From Addiction to Immune Modulation
Naltrexone was originally FDA-approved in the 1980s at 50mg to block opioid receptors for addiction recovery.
However, clinical pioneers discovered a "Biological Paradox": when you use a micro-dose (usually between 0.1mg and 4.5mg), the drug stops acting as a blocker and starts acting as a systemic immune modulator.
In 2026, LDN is now recognised as one of the most effective tools for calming the "Brain-on-Fire" symptoms of Fibromyalgia, Long Covid, and ME/CFS.
2. The Science: Flipping the "Microglial Switch"
To understand LDN, you must understand the Microglia.
Microglia are the "Security Guards" of your brain. In a healthy person, they protect neurons. But in chronic illness, they become "Primed." They get stuck in the "ON" position, pumping out neurotoxic cytokines, substance P, and nitric oxide.
LDN works through two distinct mechanisms:
The TLR4 Antagonist: LDN binds to a specific receptor on your Microglia called Toll-Like Receptor 4 (TLR4). By blocking this receptor, LDN tells the "Security Guards" in your brain to stand down. It effectively flips the switch from "Inflammatory Mode" to "Repair Mode."
The Endorphin Rebound: LDN briefly blocks your opioid receptors for 2–4 hours. Your brain senses this "deficit" and responds by producing a massive surge of Endorphins (your natural painkillers) and Enkephalins. When the LDN wears off, these internal healing chemicals flood your system, lowering your pain threshold and stabilising your mood.
3. How LDN Targets the "Trifecta"
For Fibromyalgia: It addresses the Central Sensitisation by lowering the "gain" on your nerves. It turns the volume of your body's pain signals from a 10 down to a 3.
For ME/CFS: It reduces neuro-inflammation in the brainstem and hypothalamus—the areas responsible for the "crushing leaden fatigue" and the broken sleep-wake cycles.
For MCAS: Mast cells and Microglia are in a constant "Feedback Loop." When your brain is inflamed, your mast cells stay twitchy. LDN quiets the brain, which in turn helps stabilise the peripheral mast cells.
For ADHD/Autism: By reducing the "background noise" of neuro-inflammation, LDN can significantly improve executive function and reduce the "sensory overwhelm" that often triggers an MCAS flare.
4. The "Start Low, Go Slow" Titration Protocol
Because the MCAS-Fibro system is hypersensitive, a standard "starting dose" is often too much. We see many patients fail LDN because their doctor started them at 4.5mg, causing a massive "healing crisis."
The Mend Protocol for LDN Titration:
The Ultra-Low Entry: For sensitive systems, we start as low as 0.1mg to 0.5mg.
The 14-Day Window: We hold that dose for two weeks. We aren't looking for "cures" yet; we are looking for Clinical Silence (no new side effects).
The Incremental Climb: We increase in 0.5mg increments only when the data (HRV) shows the system is stable.
The "Sweet Spot": Most patients find their "Zone of Stability" between 3.0mg and 4.5mg, though some "Ultra-Low" responders thrive on just 1.0mg.
5. Why "Data" is the Only Way to Titrate LDN
LDN is a "Goldilocks" medication. Take too little, and nothing happens. Take too much too soon, and you overflow your bucket.
This is why the Mend App is essential during LDN treatment.
We monitor your HRV (Heart Rate Variability) and Resting Heart Rate (RHR) daily.
The Signal: If we increase your LDN and your HRV drops by 20% or your sleep becomes fragmented, your system is telling us to "Hold and Stabilise" at the current dose.
The Win: We use the data to navigate the "Initial Rebound" (vivid dreams or temporary sleep changes) so you don't give up before the miracle happens.
6. Common Side Effects & How to Manage Them
Vivid Dreams: This usually indicates the "Endorphin Rebound" is working. If it's too intense, we move the dose from Night to Morning.
Temporary Insomnia: Often a sign of rapid titration. We lower the dose and add Mend Magnesium 5-in-1 (this will be available soon for everyone)to support the GABA receptors.
Filler Sensitivity: Many MCAS patients react to the fillers in compounded LDN (like lactose). We ensure our patients use "Clean" compounding fillers like ginger or microcrystalline cellulose.
This can be a great medication but requires a deep understanding of your sympotm’s and previous history, aswell as the options available to you. This is the purpose of my in depth initial 1-1 consultation, book here if you are interested.
Stay Well
Disclaimer: Mend provides educational data and clinical insights only. This content is not a substitute for professional medical advice, diagnosis, or treatment. Always consult your physician before starting or changing any medication or supplement protocol. In an emergency, call 999 or 911 immediately.
