LDN and Glutamate?


I posted this on another forum, but never got a good answer to my question.

Maybe this could be added to the list of questions for Dr Younger's webinars, @usedtobeperkytina?

I started LDN because I thought it would help decrease levels of glutamate in my brain. It is widely reported that LDN inhibits glial cells which produce glutamate on LDN pages.

Like this one:

Glutamate is the most abundant neurotransmitter found in the central nervous system. It is an excitatory neurotransmitter. Glutamate binds to a receptor called NMDA (N-methyl D-aspartate).

The NMDA receptor is the most common receptor found in the Central Nervous System. When the NMDA receptor is activated by glutamate it opens up calcium channels which cause the nerves to fire.

To summarize, when glial cells are activated they release chemicals and neurotransmitters that cause NMDA receptors to be activated which cause nerves to fire.

LDN (Low Dose Naltrexone), by its ability to inhibit microglial activation, suppresses activation of NMDA receptors by decreasing the release of glutamate neurotransmitter.​

However, LDN increases levels of beta endorphins drastically...which have been shown to enhance glutamate neurotoxicity in the hypothalamus by disrupting the calcium balance.

The effects of beta-endorphin(beta-End) on monosodium glutamate(MSG) neurotoxicity were studied via morphological observation and image analysis of neuronal areas, together with the determination of intracellular free calcium concentration ([Ca2+]i) in single neuron and radioimmunoassay for beta-End contents.

beta-End(1.0 mg.kg-1, s.c.) was found to obviously aggravate the neuronal injury in the arcuate nucleus of hypothalamus induced by MSG(0.5 g.kg-1, s.c.).

Just as MSG increased [Ca2+]i significantly, beta-End(2.0 g.L-1) itself also increased it, though the extent of elevation was smaller than that of MSG(17.0 mg.L-1).

The obvious changes of [Ca2+]i induced by both MSG and beta-End were partially reversed after pretreatment with verapamil.

On the other hand, the content of beta-End in different areas of the brain were augmented following the addition of MSG and further elevated by morphine treatment.

These findings suggest that the mechanisms of the enhancing effect of beta-End on glutamate neurotoxicity were linked to the aggravation on the disruption of intracellular Ca2+ homeostasis induced by MSG. Moreover, the fact that opioids promote beta-End release induced by MSG may be involved in the mechanisms as well.​

How can both of these things be true? Any ideas?


Well-Known Member
LDN was a horrible trial for me because it did seem to aggrivate issues that I perceived to be NMDA connected. Tramadol and an occasional Bentyl have been my best meds for my HyperPOTS and over active sympathetic system. It will moderate NMDA and other neurotransmitters. There have been some find it to be great for them and others who paradox with it. I cycle it.


Get Our Free ME/CFS and FM Blog!

New Threads

Forum Tips

Support Our Work



Shopping on Amazon.com For HR

Latest Resources