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High Levels Of Glutamate Implicated In Depression / Suicide

Discussion in 'Mind, Sleep, Stress' started by haidut, Jun 12, 2014.

  1. haidut

    haidut Member

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    The study was about SSRI effectiveness prediction, but as usual, sometimes little gems leak out of the study that are useful to people with Peatarian mindset:

    http://www.newscientist.com/article/dn2 ... sants.html

    "...In the latest study, Turecki and his colleagues measured the levels of about 1000 miRNAs in the brains of people who had committed suicide. These were compared to levels in brains of people who had died from other causes. A molecule called miRNA-1202 was the most altered, being present at significantly lower levels in the brains of people who died from suicide.
    Crucially, this molecule seems to damp down the activity of a gene involved in glutamate signalling in the brain. That's significant because recent research has highlighted the importance of glutamate signalling in depression."

    This would explain why drugs like tianeptine are so effective in depression since their effects on serotonin are actually not as prominent as their effects on lowering glutamate in the brain.
    Finally, as a tip to the ones without access to tianeptine - I posted a study on theanine being a potent glutamate antagonist due to its similar chemical structure. Not surprisingly, there are several studies on PubMed reporting antidepressant action of theanine in animal models.
     
  2. khan

    khan Member

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    Have you tried memantine, which according to wiki is NMDA antagonist?
     
  3. dukez07

    dukez07 Member

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    Memantine is a very good mood stabalizer from my experiences with it, and has a good anti-depressant action too for some, during the initial stages of use. Some are sensitive to its anticholinergic effects, but it actually improved cognition for me. But then, on the flip-side, the NMDA (glutamatergic) agonist, sarcosine, also has an acute anti-depressant effect for me. So my issues with the NMDA receptor seem to be more related to hypofunction.
     
  4. OP
    haidut

    haidut Member

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    If you are going to try an NMDA antagonist, I'd go with magnesium as it is one of the most potent and well-known ones. There have been some news lately on ketamine (also an NMDA antagonist) causing rapid recovery from severe depression (several days). There are also studies on PubMed of magnesium glycinate or magnesium taurate also causing rapid recovery (7 days) from depression.

    Rapid recovery from major depression using magnesium treatment. - PubMed - NCBI

    "...Case histories are presented showing rapid recovery (less than 7 days) from major depression using 125-300 mg of magnesium (as glycinate and taurinate) with each meal and at bedtime. Magnesium was found usually effective for treatment of depression in general use. Related and accompanying mental illnesses in these case histories including traumatic brain injury, headache, suicidal ideation, anxiety, irritability, insomnia, postpartum depression, cocaine, alcohol and tobacco abuse, hypersensitivity to calcium, short-term memory loss and IQ loss were also benefited."

    That's a pretty impressive list of conditions benefiting from magnesium supplementation! Also, it supports Ray's view of glycine and taurine being beneficial amino acids and magnesium glycinate being a good form of magnesium to take.
     
  5. Such_Saturation

    Such_Saturation Member

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    The glutamate system is crazy. I found these on lithium and lsd:

    Lithium acutely inhibits and chronically up-regulates and stabilizes glutamate uptake by presynaptic nerve endings in mouse cerebral cortex

    <<In experiments on mice, Sealfon also found that LSD -- in order to
    produce the effects sought after -- must simultaneously act on a
    receptor regulating glutamate, the principal excitatory
    neurotransmitter.
    "While the LSD is binding to the serotonin part of this complex, it
    takes glutamate and serotonin together to create the unique changes in
    the cell that occur with LSD," Sealfon told AFP.
    When mice under the influence of LSD were given a second drug
    targetting only the glutamate receptor, it neutralised the
    hallucinogenic effect of the LSD, said the study, published in the
    British journal Nature.>>

    Also Piracetam: Piracetam in the treatment of schizophrenia: implications for the glutamate hypothesis of schizophrenia. - PubMed - NCBI

    [Relationship between facilitatory effect of piracetam on memory and glutamate receptors]. - PubMed - NCBI
     
  6. mother

    mother Member

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    Interesting. Has anyone on this forum tried magnesium glycinate or magnesium taurinate for the purposes indicated in haidut's post? Is magnesium glycinate a better alternative than magnesium taurinate? Also, could you recommend a good source for these supplements?
     
  7. Blossom

    Blossom Moderator

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    When I first started my Peat inspired approach I used magnesium glycinate a few times with no problems. It wasn't specifically for high glutamate but just because I felt I needed a little extra magnesium at the time. I then switched to Epsom salt baths and gradually stopped those as well as I started to feel better. I used Pure Encapsulation brand at the time because it was the one I found without additives. The capsule was cellulose so I just emptied the contents out of the capsule and took the magnesium glycinate. There might be better brands. Nowadays if I'm looking for supplements I check Food and supplements without questionable additives - Toxinless for recommendations.
     
  8. Vinero

    Vinero Member

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    so, things that reduce glutamate:
    -Theanine
    -Aspirin
    -Taurine
    -Thiamine
     
  9. OP
    haidut

    haidut Member

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    In general, anything that raises GABA will oppose/lower glutamate. This explains why taurine and theanine both lower it since they both stimulate GABA release. Theanine is also a structural analog of glutamate, almost like an anti-metabolite so that's probably another reason it opposes glutamate. Other GABA agents that should lower glutamate are niacinamide, progesterone, pregnenolone, saturated fat, tryptophan-deficient protein, glycine, proline, alanine, etc. As you all know, these substances are all known to be sedative in high doses, which suggests GABA release.
     
  10. mother

    mother Member

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    While looking into making Magnesium Bicarbonate, it cautions not to combine this with a meal, snack, supplement, or drink that contains calcium. So how does one dose with Magnesium Bicarbonate(MB) and still consume calcium as per RP? It also mentioned there should be a proper ratio of magnesium to calcium. Can someone please simplify this for me? I want to know when, how and with what or what not to consume MB with.
     
  11. OP
    haidut

    haidut Member

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    Since to me it tastes almost like water, I drink MB on its own and on an empty stomach. I drink about 300ml in one sitting, and that provides about 500mg of elemental magnesium. It used to be very sedative for me but now the effect wore off suggesting I am becoming replete in magnesium.
     
  12. pboy

    pboy Member

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    very interesting topic...gonna have to read more when I have time. I wasn't aware Peat thought high glutamate was not good... is it part of a stress cascade? Ive experimented with some gaba herbs in the past, they give a nice similar to relaxing on the beach state of mind, but can become powerfully sedative

    I figured elevated glutamate might be part of an inflammation response when I kept reading that it was elevated after certain plant toxins or microbe byproducts
    were taken in...but also read its part of focus and memory and some other stuff, so I haven't quite formed an opinion or have anything experiential to go off
     
  13. OP
    haidut

    haidut Member

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    Some levels of glutamate are certainly physiological. For instance, activation of the NMDA "receptor" by co-agonists like glycine is necessary to maintain a healthy mind and avoid becoming schizophrenic. Glycine is currently in clinical trials for treating schizophrenia. Daily dosage is 30g twice a day for a total of 60g daily.
    But chronically elevated levels of glutamate are neurotoxic and can lead to a number of neurological disorders much worse than depression - Toxic Dementia, Parkinson, Alzheimers, Friedrich Ataxia, etc.
     
  14. skominac

    skominac Member

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    Yes, I have. I started feeling dizzy and high after about 30 minutes, and I stayed like that for 3 days! I learned that Memantine has a half-life of 60 to 100 hours. It is a very powerful drug, and I will never touch it again.

    I was simply looking for something to help with my occasional headaches from glutamate toxicity. Well, it worked. The headache was gone. I just did not expect to get several days of tripping along with it.
     
  15. OP
    haidut

    haidut Member

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    Virtually all NMDA antagonists in sufficient doses will cause dissociation/de-realization and as such should be used rather cautiously. Even magnesium can cause that but what makes it relatively safe is that it will induce loose stools before it reaches those levels. However, for IV magnesium it's tripping effects are very well known and hospitals are careful in how much they give for that very reason.
     
  16. Parsifal

    Parsifal Member

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    Is the cause of depersonalization also from low glutamate?
     
  17. OP
    haidut

    haidut Member

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    Don't know if it is low glutamate, but it is related to dysfunction of the glutamatergic system:
    http://www.ncbi.nlm.nih.gov/pubmed/21742442
     
  18. barefooter

    barefooter Member

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    Thanks haidut, this is very interesting. I actually suffered from depersonalization and derealization this spring, and I'm just getting over it now. It was by a long shot the most terrifying thing I have ever been through. I have actually tried recreational ketamine in the past, and now thinking about it I can see how the experience is similar. Just that when it's for 30 mins it can be fun, but when it's for months it sucks.

    I think my depersonalization was caused by chronic psychological stress, as I was at a cult in Bali with my girlfriend, and both the cult and GF (now ex) were driving my crazy, literally. However, asian countries are known for cooking with lots of MSG, so I wonder if that was a factor too. There really doesn't seem to be a lot of research on this condition, and there are lots of people who can't really get appropriate help to get over it. It becomes a vicious feedback loop, because you become afraid of the moments when you feel depersonalized, and the anxiety triggers more of, which can really spiral downward.

    I got out of the hell of it by getting out of my toxic relationship and back to a low stress life where I was really taking care of myself well. However, it wasn't until I got my sleep really dialed in that I felt like I was mostly recovered. I think my circadian rhythm was way out of whack, causing things to often feel dreamy during the day as I was never fully awake.
     
  19. Jib

    Jib Member

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    I was recently put on memantine. About a week ago.

    Initial dosage was 5mg 2x a day. For the first several days I felt heavily dissociated. I just cut a pill in half and took 2.5 mg instead of 5mg. I went down to 5mg a day after the first few days because the dissociation was so overwhelming I couldn't handle it.

    I'm not giving up on it yet, but I really felt bizarre. It's good to know that it's the memantine doing it because I felt like I was in the Twilight Zone or something.

    2.5mg might seem very low, as a more typical dose seems to be 10mg 2x a day. But even 5mg a day was making me feel really trippy.

    I'm very curious to know more about this stuff. I've been very reluctant to take any pharmaceuticals, but some cursory research makes it seem like memantine might be helpful in small doses.

    I'm sticking it out through the side effects (feeling heavily depersonalized/dissociated, also some flu-like symptoms although I'm not sure if that's the medication or not)...to see if it might be beneficial in the long-term.

    But honestly I feel like 2.5mg might be much more appropriate than 10mg and even 5mg. This is powerful stuff from what I can tell, and it makes me a little nervous.

    Very curious what other people's thoughts are on memantine.
     
  20. James_001

    James_001 Member

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    How did you get your sleep in order? I think I may have been experiencing the same thing, and for me it also was caused by intense psychological stress. Also, do you take thyroid? I agree it is a difficult hole to transcend simply because a lack of sleep drains all of your energy required to solve the problem and thus the cycle repeats itself.

    I am also interested in this cult if you don;t mind sharing. Not that I want to join, just curious about the working of the cult and how you ended up there etc....

    If it is too difficult to speak about I understand.
     
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