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Excitotoxicty,NMDA, help guide treatment?

Discussion in 'General Treatment' started by PokerPlayer, Jan 17, 2012.

  1. PokerPlayer

    PokerPlayer Guest

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    So I have done a bit of reading and trying to put all the pieces together.

    In short, I think my cfs looks very similar to a lot of peoples, but my underlying reason for it is much different. I think my underlying reason is the kindling theory. My multiple frontal lobe concussions have caused a brain that is hyper sensitive and causes overstimulation, causing me to feel wired and exhausted. I think it comes down to NMDA receptor issues and excitotoxicity.

    NMDA and excitotoxicity possibly explain every single reaction I have to supplements, and even meditation! Thats right, remember me posting about medition causing increased anxiety/depression? Well it is hypothesized that deep meditation can activate the nmda receptors and raise serotonin. Too much serotonin in a sensitive brain = excitotoxicity.

    Even vitamin d calms down excitotoxicity http://www.jneurosci.org/content/21/1/98.full.pdf , and that is its main mechanism of action in raising my crash tolerance. Remember, in me, anything that causes brain fog/brain slow down = calm mood, increased physical crash tolerance, no depression, but downside is a fogged out apathy.

    Folic acid is also thought to modulate the nmda receptor http://www.ncbi.nlm.nih.gov/pubmed/18789921
    Methyl b12 reduces nmda excitotoxicity http://www.iovs.org/content/38/5/848.full.pdf html

    A big question I have though, is why have I gotten to the point where I feel nothing when I take folic acid, b12, and vitamin d? I recently just crossed a threshold where they do not cause brain fog or anything, its like taking a sugar pill. It seems as though my current excitotoxicity state is too much for these natural remedies.

    I am going to a doctor appointment in an hour and the doctor previously recommended gabapentin but I declined at the time because I wasn't depressed or anxious, just foggy. I am also going to talk to the doctor about klonopin. I am very curious as to what my reactions to gabapentin and klonopin could be.

    I also found this little article on Head injuries and kindling excitotoxicity causing cfs. But it seems like a lot of things I read that don't work, with too much certainty to the theory. http://www.ncf-net.org/forum/neurontin98.htm
  2. alex3619

    alex3619 Senior Member

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    Hi PokerPlayer, any model that invokes NMDA might be linked to Pall's NO/ONOO cycle, and may not be about kindling at all - its an alternative explanation, not saying it is right. Its also a complementary explanation - they could both be right. The NO/ONOO work links into methylation issues as well. Classically it is magnesium that is used to treat NMDA I think. I have never used it for this purpose though, I hope someone else can comment. Bye, Alex
  3. PokerPlayer

    PokerPlayer Guest

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    The thing that just doesn't make sense to me though is that I can't even meditate without my brain going crazy. If I meditate in the morning, at night my brain will be freaking out and racing, as well as increased feeling like my brain is actually electrocuting itself.

    I just have to think that brain nmda excitotoxicity has to play a bigger role in my illness than most. I have pretty similar symptoms to a subset of people here (wired but tired, post exertional malaise, brain fog), but I had slow onset that was in my opinion precipitated by a lot of frontal lobe concussions a few years prior.

    Just got some gabapentin from my doctor, as well as klonopin (which is a last resort). Other options I am thinking would be good would be lamictal.

    I see what you are saying, alex3619, that the supplements b12, d3, and folic acid calming my brain nmda activity may be due to some process which directly affects the underlying immune problem I have, which then lowers nmda activity.
  4. Valentijn

    Valentijn Activity Level: 3

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    Gabapentin and Klonopin are both used to attempt to counter the symptoms of high levels of glutamate. High glutamate levels is likely a common problem in people with with ME/CFS, and could be causing your symptoms as it is an excitatory neurotransmitter.

    Something else that might work is N-acetylcysteine (NAC) which could act to directly lower glutamate levels by combining with the glutamate to form glutathione.
  5. PokerPlayer

    PokerPlayer Guest

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    So I took 300mg nac and it has caused diarrhea. So far the ganapentin at 300mg.takes the edge off the anxiety and depression and tinnitus, but not much. I think I want to switch to lamictal for more of an antidepressive effect. I also think working on the gut would help a lot and I have threelac to try
  6. Nielk

    Nielk

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    Hi Pokerplayer,

    I can give you two pieces of advice from my past mistakes:

    #1- Only try one new medicine or supplement for a while. If you add more than one, you will not know which one is working or which one is giving you side effects.

    #2- With Gabapentin - you have to start slow and gently up the dosage to a level that you feel is beneficial yet doesn't have side effects. You have to have patience to see this through - to make sure that you gave it a fighting chance.

    I know that I said two but, I will add a third

    #3-You mentioned the fact that you got a prescription of Klonopin. Regard that prescription as a real last resort. I wish someone had warned me against it BEFORE I started on that road.

    Good luck,
    Nielk
  7. PokerPlayer

    PokerPlayer Guest

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    Thanks nielk.

    Yeah, I definitely regard klonopin as a last resort. So far I have only taken .125mg's on two occasions, and the effects are definitely noticeable. The bad thing though, is that I feel it is just enabling me to push my body more, and not really much positive.

    The gabapentin I know will have to be slowly raised to a higher dosage for full effect, but I have been reading into lamictal and think long term it would be a better choice if my body could tolerate it, if not I would just get back on the gabapentin.

    Thanks for the advice.

    Also thinking about doing some gut protocols to help with the constant depression and excitotoxicity I am having. I have threelac to try, and then maybe some of Hips protocols he posted on the gut and prebiotics.
  8. dannybex

    dannybex Senior Member

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    Theresa Vernon links overstimulation and the extra 'wired but (eventually) tired' feeling to copper toxicity and usually low zinc. I'm not sure if I agree, but I have stabilized a bit by cutting out high copper foods, any copper supps. Anyway, here's a link to her article:

    http://www.tvernonlac.com/copper-toxicity.html

    "Physically, the copper build up interferes with proper conversion of thyroid hormone at the cellular level. It also disturbs zinc balance, interfering with adrenal hormone production and this weakens the immune system. The impairment of both thyroid and adrenal gland function causes the most common copper toxicity symptom: fatigue.

    It inhibits cortisol (glucocorticoid) production which causes hypoglycemia and increased inflammation, and increases aldosterone (mineral corticoid) production which enhances brain activity and can give a feeling that the mind is racing.

    It is stimulating and irritating to the nerves and can lead to headaches including migraines, neuralgia, such as sciatica or trigeminal neuralgia, and other neurological conditions..."

    I tried Gabapentin years ago...it will make you groggy, tipsy, but ended up getting off of it as it made me too weak overall (but I was also reluctantly trying other drugs, at my employers insistance ("go to a real doctor!").

    While I do reluctantly take a minimum amount of clonazepam now, what has helped in the last 3 months is Seriphos -- helps lower cortisol -- and also the amino acids lysine, glycine and ornithine. Lysine helps lower cortisol, glycine helps process high salicylate foods (which can be incredibly stimulating) and ornithine helps with sleep.

    p.s. If you check the b12 threads, some have found benefit by backing off the b12 for a few days, then taking it say, every other day or so...
  9. Nielk

    Nielk

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    Pokerplayer,

    Like I said before, I would stick with one thing at a time. You will never know if Gabapentin is good for you until you give it a real try.
    The reason I'm so insistent with this is not because it helped me personally. I have tried it years ago and it didn't help me but, I know of other patients where it made a huge difference. I met a patient in my specialist's waiting room and he told me that for years he couldn't get out of bed. He is some kind of famous writer. Gabapentin saved his life.
    He now travels all over the world and leads a normal life because of Gabapentin. I asked the nurse how come he had such a miraculous result whereas for me it didn't do anything and she replied that everyone is different.
    If you give this a good try and a shot that maybe you are a good res-ponder, then you will know for sure. If you don't try it, you will never know.
    If it doesn't work out, you will have the chance to try all kinds of other treatments. (one at a time)
  10. PokerPlayer

    PokerPlayer Guest

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    Hmmm.... interesting nielk. I am the agitated/depressed type of cfs/me. I do better when my brain is calm, even brain fog is welcoming. All the supplements that I do that help me actually increased my brain fog: folic acid, b12, vitamin d3, low dosage celexa. I will have to think about giving gabapentin a real shot. Lamictal is much better for agitated depressive type, and I have some bad depression going. I was just going to switch back to gabapentin if lamictal was no good.

    And dannybex: Taking zinc actually is a big clue for me. It causes severe agitated depression in me. Zinc causes extreme excitotoxicity. When I was doing better I used to take it every night. I actually tested high in my blood levels so I stopped about a year ago. Lately, I tried it again and it caused severe excitotoxicity reactions.

    I can't take methyl b12 anymore because it also causes excitotoxicity.
  11. markmc20001

    markmc20001 Guest

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    Heya sir.

    I have issues that I would describe as excitotoxcity. Your situation sounds somewhat different because you have a definite injury.

    Caffine makes it miserable for me, so does celexa.

    You may want to look up porphyria and see if that makes any sense as well. Can't remember now, but at the time it seemed like excitoxcity and porhyrias may feel somewhat similar.

    Porphyrias are a dysfunction of the heme I believe.
  12. kaffiend

    kaffiend Senior Member

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    Taurine, magnesium malate and l-theanine have helped with my brain freaking out from exposure to bright light or fast motion (such as while driving) or just simply trying to read/focus.

    Riboflavin (b2) and benfotiamine (a form of thiamine, b1) in high doses three times per day (100mg/3X) in addition to methyl b12 and b-complex have also been quite helpful with brain fog and migraine-like light sensitivities without headache.
  13. ramakentesh

    ramakentesh Senior Member

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    There may be increased NMDA mediated excitotoxicity or at least increased excitation of the central system because of many factors - so its hard to automatically assume that some speculative etiologies have to apply to explain it.

    Here is one that you may not have considered. Some patients may have reduced vasoconstrictive responses to angiotensin II meaning that their sympathetic system has to activate excessively to compensate. therefore they experience increased heart rate, postural autonomic abnormalities and all the consequences of sympathetic excess.

    Often I read statements in these forums that seem to be based on presumption.

    I hear a number of people have had benefit from NMDA antagonists. Huperzine A is a good candidate for a start.
  14. ramakentesh

    ramakentesh Senior Member

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    I have never seen and compelling evidence that there is excitotoxicity in CFS that results in measurable damage or consequence. Perhaps abnormal or reduced cerebral blood flow and sympathetic excess explain these symptoms?
  15. Graeme

    Graeme almost there...

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    Hi PokerPlayer. I can't meditate either due to the excitotoxicity that ensues. It seems to get the chi flowing, feeding the excitotoxicity loop. I've experienced the same thing with acupuncture and reiki; I feel better for several hours and then I'm speedy and all messed up.

    My read on things is this problem is caused by the immune system, and I've no doubt it's this that's keeping energy down. Oxidative stress is driving a superoxide/NMDA receptor loop. I've derived a lot of relief with wormwood in the past which apparently works by increasing SOD levels. Magnesium is great stuff too, though it's not really well absorbed through the gut. Transdermal and IV worked best for me. IM did very little and I've no idea why that is. You also might want to try HB12. I can't take it myself but it's a lot less stimulating than MB12.

    Dextromethorphan, guaifenesin GHB, benzos, opiates and alcohol (all the fun stuff) have all increased my energy in the past -while they were still tolerated. However the only ones I would think of recommending from the bunch are guaifenesin and GHB. I believe they're actually some of the better drugs one could use for this illness, especially with pronounced excitotoxicity or neuralgia, though who knows about long term effects.

    I'm actually trying to make my way through Martin Pall's book right now. The technical stuff is mostly over my head, as I've no background in this stuff, but as far as I'm concerned his hypothesis is the one that best describes what I'm dealing with.
  16. ramakentesh

    ramakentesh Senior Member

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    There is great danger in self diagnosis. What you think maybe excitotoxicity may relate to a completely different neuronal system. I often hear opinion posed as fact.
    Very often I read someone suggest that something worked for them, then they pick one particular activity that the substance has of many and then use that to demonstrate a reason for why it helped as fact. Dangerous stuff in my opinion.
    ahimsa and Valentijn like this.
  17. PokerPlayer

    PokerPlayer Guest

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    Hey Graeme, Its nice to be able to find a few people out there like me. Believe it or not, your meditation experience is maybe the 3rd person I have ever actually read about that is similar to mine. The only thing is that meditation may increase excitotoxicity symptoms temporarily, but continued meditation for a few more days may actually eventually help to stop the agitation. Problem with me is that the psychological pain (anxiety/depression) just gets to extreme and severe to think of trying anything like that again.

    When I was doing a lot better, I remember feeling really depressed at night after meditating in the mornings, I have it in my journal that I got rid of this feeling a year and a half ago by upping my magnesium to 1 gram per day oral dose. Well, I tried doing that recently and nothing happened. My excitotoxicity symptoms are really severe, like severe ringing in the ears, brain feels like it is electrocuting itself, leading to bad anxiety and depression. I have been on gabapentin and it has helped about 50%. The severe depression and anxiety aren't severe anymore, just moderate, still not great.

    I am thinking about giving lamictal a shot. It says it calms electrical signals in the brain and manipulates glutamate, so it may be great. Plus I am in contact with some people who said it helped their psychiatric symptoms of cfs/me.

    I definitely cannot tolerate alcohol right now. Opiates aren't a good idea. Dextro doesn't sound good long term. Heard of GHB and guaifenesin. When I was doing a lot better vitamin d3, folic acid, and methyl b12 were the things that calmed down the body and the brain the most.
  18. PokerPlayer

    PokerPlayer Guest

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    Doing the best I can though. Wish a doctor could help but I wouldn't trust my life to them at this point. Only a few docs in the country I would do whatever they said.
  19. ramakentesh

    ramakentesh Senior Member

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    I understand your frustration and your quest for therapy but id say that most of the most recent and well constructed research on CFS hasnt generally supported many of the older paradigms and theoretical ideologies. What Im getting at is that its very important to keep an open mind about everything you are experiencing. What you believe may be one thing - which may at that time seem to fit a particular etiological theory at that time - may turn out to be something else entirely as demonstrated in future peer reviewed reputable research.

    An example:

    A guy emailed me to tell me how effective a particular supplement was for his cognitive function. And ofcourse he instantly regailed me with the reasons why because of NMDA excitotoxicity and a bunch of other theories. Which could all be totally correct - dont get me wrong - but the supplement has some pretty impressive effects that do not relate to the NMDA pathways.

    if something works - that is great - but there may be different reasons for that than you expect or some cases even believe.
  20. PokerPlayer

    PokerPlayer Guest

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    I see what you are saying. For me my back is kind of against a wall though. I had severe anxiety and depression and LOUD constant never ending ear ringing. Basically it made me feel psychotic. My brain hurt like it was electrocuting itself. It was an extreme symptom that needed instant attention. I developed this system instantaneously after I overdid it physically a few weeks ago. All of a sudden my ears started ringing like crazy, and my brain started hurting really bad, and my mind started racing.

    I had to go with what made the most sense, and leave the theories for later. My only options for immediate symptom management are mostly psyche drugs. Gabapentin has been helpful, not great, but not bad. I think lamictal may be a lot better in stopping the electrocution like symptom and brain chatter that goes with it.

    Still want to look into curcumin too.

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