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LDN and Glutamate.

Ema

Senior Member
Messages
4,729
Location
Midwest USA
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.

http://www.ldnresearchtrust.org/node/188

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.

http://www.ncbi.nlm.nih.gov/m/pubmed/11938958/?i=2&from=/10374630/related

How can both of these things be true? Any ideas?
 
Messages
37
Location
NZ
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:



http://www.ldnresearchtrust.org/node/188

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



http://www.ncbi.nlm.nih.gov/m/pubmed/11938958/?i=2&from=/10374630/related

How can both of these things be true? Any ideas?
I don't know anything about LDN but - I just wondered if some of the people taking it found they had an increased sensitivity to MSG and foods containing glutamate? Because I made a mistake recently of taking straight flaxseed oil (simply because I had it) rather than a usual blended mix formula of EFAs (omegas 3,6,9) - and I got severely out of balance. I wouldn't recommend it to anyone with cfs/me. Very badly disrupted sleep with big meals esp. with msg. I wonder if its the same kind of thing, by any chance.
 

Mor

Messages
32
How can both of these things be true? Any ideas?

I know this is an old thread, but I was thinking of trying LDN in the future, and would like the answer to your question.

Has LDN caused anxiety for anyone?
 

picante

Senior Member
Messages
829
Location
Helena, MT USA
I know this is an old thread, but I was thinking of trying LDN in the future, and would like the answer to your question.

Has LDN caused anxiety for anyone?

I don't think it caused any anxiety for me, but I did suspect that it was increasing my neck pain. That's when I stopped taking it. I have read that there are lots of NMDA receptors in the neck, but would like to know more.
 

JES

Senior Member
Messages
1,318
I know this is an old thread, but I was thinking of trying LDN in the future, and would like the answer to your question.

Has LDN caused anxiety for anyone?

LDN also blocks inflammation and reduces pain through antagonizing TLR4 receptor that regulates microglial activity (link), so it can also reduce anxiety, assuming that the anxiety is driven by inflammation in the brain. For me it perhaps increased anxiety slightly in day one and two, in long term it definitely helps me more than does damage.
 

Mor

Messages
32
LDN also blocks inflammation and reduces pain through antagonizing TLR4 receptor that regulates microglial activity (link), so it can also reduce anxiety, assuming that the anxiety is driven by inflammation in the brain. For me it perhaps increased anxiety slightly in day one and two, in long term it definitely helps me more than does damage.

I was wondering if the trouble sleeping that many have while on LDN was attributed to glutamate neurotoxicity?
 

JES

Senior Member
Messages
1,318
I was wondering if the trouble sleeping that many have while on LDN was attributed to glutamate neurotoxicity?

I doubt it, but I could be wrong. LDN has been reported to help in so many neurodegenerative conditions (Parkinsons, MS, etc.), I have never heard about anyone whose disease got worse from taking LDN. So I find it unlikely it would cause neurotoxicity to any significant degree, also bearing in mind that the 50 mg dosage is FDA approved for alcohol/drug dependence and the medication is perfectly safe even in that dosage.
 

Mor

Messages
32
I doubt it, but I could be wrong. LDN has been reported to help in so many neurodegenerative conditions (Parkinsons, MS, etc.), I have never heard about anyone whose disease got worse from taking LDN. So I find it unlikely it would cause neurotoxicity to any significant degree, also bearing in mind that the 50 mg dosage is FDA approved for alcohol/drug dependence and the medication is perfectly safe even in that dosage.

I found this:
http://forums.phoenixrising.me/inde...nxiety-on-ldn-and-just-push-through-it.42666/

Also 50mg wouldn't seem safe for someone with CFS.

Overall I think it's possible that the anxiety (likely causing the lack of sleep) may be glutamate related.
 

Gondwanaland

Senior Member
Messages
5,092
Because I made a mistake recently of taking straight flaxseed oil (simply because I had it) rather than a usual blended mix formula of EFAs (omegas 3,6,9) - and I got severely out of balance. I wouldn't recommend it to anyone with cfs/me. Very badly disrupted sleep with big meals esp. with msg. I wonder if its the same kind of thing, by any chance.
Interesting, I had been taking flaxseed oil + Borage but had to stop for the same reasons, and now glutamate hell broke loose.
 

perchance dreamer

Senior Member
Messages
1,686
I got insomnia from flaxseed oil years before I started taking LDN. Now I eat chia seed gel every day and have no sleep effects from it.