Author Topic: The Use of Lithium to alter glutamate reception  (Read 1998 times)

[Buddie]

Re: The Use of Lithium to alter glutamate reception
« Reply #10 on: November 06, 2019, 07:05:04 pm »
Ok,

The "Illustrated guide," simply states that lithium will down regulate NMDA (N-methyl-D-Aspartate, a specific, powerful type of glutamate receptor)  One of the references in that guide, "Potential Mechanisms of Action" states:

https://sci-hub.tw/https://www.ncbi.nlm.nih.gov/pubmed/23371914
(If you want to read the paper, but get Russian letters, thE letters are saying "solve the captcha" so just type in what you see in the window, click on the "button," and you will get the whole paper.)

THIS IS THE REASON I PERSONALLY THINK THIS COULD BE HELPFUL:

"Lithium competes with magnesium at this binding site, and acutely stimulates the NMDA receptor, which in turn increases the availability of glutamate in the post-synaptic neuron [107]. However, with chronic lithium administration, glutamate neurotransmission stabilizes as the NMDA receptor is downregulated, and  this increases glutamate re-uptake, which restores glutamate transmission. This is one possible mechanism through which lithium achieves its long-term mood-stabilizing effect as  well as its anti-manic properties [108–110]."

Remember, it works on 1/2 dozen other things too, so that is why it might be less painful to some, and more painful to others.  I still have to think about it for a long time, but maybe it can be applied "homeopathically."  You take 1/4 of an orotate pill.  It revvs you, then you downregulate, and take 1/2?  Hmmm.

[...]
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The Use of Lithium to alter glutamate reception
« Reply #11 on: November 06, 2019, 07:12:10 pm »

Took,

I am convinced that after a few months to a year off tops, all of our issues are glutamate.  I would not preoccupy my thought process with antagonizing GABA or what will affect GABA, think instead, what will reduce the number and potential of glutamate receptors?  That is why I like lithium so much.  It SHOULD do what we want it to do, make glutamate hang out in the synapse just a little longer, and have the receptors respond by reducing.  Will it happen for us?:  Who the heck knows, but I think it is worth a shot for that reason alone.

I stand behind what I said about 50-50, I think some will be calmed, others revved, but that is just my "gut feeling."

[...]
YPNS. RYTHIT, AWYAGTH, KG!

Ram,  just for clarification let's lay out your thesis here.  So you believe that the Glutamate receptors are stuck in upregulation due to the initial downregulation of the GABAA receptors.  And you also believe that, regardless of the current state of the GABAA receptors, that finding a way to suppress and even reduce the numbers of Glutamate receptors will bring a reduction in our symptoms.  Have I got that right?
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The Use of Lithium to alter glutamate reception
« Reply #12 on: November 06, 2019, 07:14:54 pm »
Took,

Almost.  My thesis is that taking benzos floods the synapse with Chloride ions (Cl-) released from the GABA-A ligand gated ion channel.  These Cl- ions halt many cascades, many of which by neutralizing the Ca+2 ions in the synapse.  All of that part is actually not theory.  That is 100% proven fact.

Then my thesis is that the body responds by looking to maintain homeostasis.  So in response to, "oh, we have too many Cl- ions," your GABA-A receptors "respond," by downregulating.   This is standard benzo healing thinking.  But also in response to, "where did all of those Ca+2 ions go?" your NMDA (and potential other types of glutamate receptors) upregulate.

And my thesis continues that the body is designed to upregulate.  We "learn" anything in our mind and nerves by upregulating NMDA, and in general we are designed to build and rebuild.

But why should something we "rebuilt" dissipate? The answer is, I don't think it will, and that is the story of protracted withdrawal.  That is the part of my thesis that is not proven, but I can feel it.  In my mind and in my nerves and in my bones, like 2+2 is 4 I believe that to be true, and my neurologist agrees with me. 

And to be clear, I do not think we need to "suppress" glutamate.  We need to give those NMDA receptors a damn good reason to disappear.   I think if we could be put in a medically induced coma given an IV with glutamate to the point just below going into a seizure we would be cured in a month.   

In the absence of that, there is a lot of good research that an increase in serotonin at the synapse would do it.  I have been hesitant to discuss that at length because in general most people here would not be open to taking an SSRI after having such a bad experience with at least one psyche med, and I do not blame them.  And you can increase serotonin with supps, but that method is so fraught with peril that until I can get clean and try it on myself, I am not posting that method at all!  I just bought a higher level biochem book to help me work out the bugs.

The Lithium idea shows promise because it seems that is will simultaneously reduce Ca+2 gated reactions, AND slow glutamate transport out of the synapse.  By having glutamate in the synapse but reducing the downstream reactions, it could "trick" the body into downregulating NMDA.  It is postulated but not proven, that kidney damage not withstanding, that is the reason biopolar patients who respond well to Lithium often get better the longer they are on Lithium while other meds tend to "peter out."

And finally, when we achieve this, we will not have reduced our symptoms, we will be cured, and by cured I mean "restored to neurotypical."  We will be able to eat what we want when we want, and do what we want when we want.

At least that is the thesis.

[...]
YPNS, RYTHIT, AWYAGTH, KG!
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The Use of Lithium to alter glutamate reception
« Reply #13 on: November 06, 2019, 07:30:05 pm »
All,

Think about it this way: Benzos do one thing.  They attach onto your GABA receptors causing them release GABA and open a channel and let negatively charged Chloride anions through (Cl-)  That is it.  Everything that happens from there is how our bodies adapt to that unnatural activation and outpouring of Cl-.  GABA receptors are everywhere, most notably near other receptors so the Cl- anions can say "stop."  Stop transmitting other things.  Stop whatever you are doing. 

Previous thinking had us believe we are sick because our GABA receptors start to disappear as we trigger those Cl- anions with benzos, and that may be a part of it, especially in the "tolerance" phase.  But I am not in tolerance, the same little dose of Valium calms me, and a little bit more makes me sleepy.   Certainly anyone here in the protracted section is no longer dealing with "tolerance," so what is going on?

Because of the excessive GABA and Cl- anions, our glutamate receptors respond by increasing in number, and by a long elaborate mechanism, those that open ion channels open easier, and as FnF mentioned LTP, or Long Term Potentiation, means they let more Calcium cations (Ca2+) thru.  The glutamate receptors are also everywhere, and glutamate and its Ca2+ cations tell everything to "go go go," and are the source of ALL of our protracted pain.

So to get well, to find an active cure, we need to find something that will reduce the number of glutamate receptors and the Ca+2 cations they let thru.  Of the glutamate receptors, those called NMDA are the most powerful.  Some of the studies I have read talk about methods that reduce NMDA "receptor count" and "EPSC" and "EPSV," Excitory Post Synaptic Current / Voltage.  That is the Ca+2 cations.  Reducing those things is "scrubbing away the receptors."

Then the papers talk about RNA activity.  RNA is how our DNA tells our nerves what to do.  When you reduce RNA activity for the transcription (signaling) to nerves to make NMDA proteins, you have "scrubbed away the memory" of those NMDA receptors at the genetic level. Then we are truly cured.

Upregulating GABA receptors is relatively easy.  The body is designed to grow.  Downregulating glutamate receptors is much harder, and that is why some people are sick for a long time. Slowing RNA activity is harder still, and that is why NMDA are "kindled," as in some one who is "well" does something that pokes his NMDA receptors like alcohol, an antibiotic, a flu shot, whatever, and his NMDA receptors go back to the sick state.  They do not grow back "wrong," they just "remember" the state of having too many, and letting too much current thru, and we kindle.

That is the entire depth of my knowledge at this point, except for the methods we are discussing like serotonin, glutamate itself, and lithium.  Those are discussed in this thread.  Right now those SEEM to be the best shots for the protracted.  Will they work?  I have no idea.  Exactly how does all of this happen?  I had to take a break from studying neuroscience to refocus on biochem because I do not know enough biochem to take my understanding deeper.  But that is my job right now, and I am on it. 

I hope that explanation was helpful to anyone trying to understand our goals.

[...]
(YPN, RYTHIT, AIYGTH, KG!)
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The Use of Lithium to alter glutamate reception
« Reply #14 on: November 06, 2019, 07:32:16 pm »
[...] and All,

I have tried a few NMDA antagonists and inverse agonists, and so have other buddies.  For reasons I cannot explain, in me they revved me up, and others had no benefit.

Inhibitors are a different story.  If you have ever been in a wave and taken a drink of alcohol and had the wave "magically vanish," that is the alcohol inhibiting the current flow through your NMDA.  The problem with that of course is the rebound, which happens in neurotypical people too, but can be quite severe in the sensitive among us.  Plus, alcohol abuse isn't going to help us heal. But the fact that it DOES make us feel better in that instant just proves that lowering the current long term is a big part of the key to the cure.

[...]
(YPN, RYTHIT, AIYGTH, KG!)
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The Use of Lithium to alter glutamate reception
« Reply #15 on: November 06, 2019, 07:38:02 pm »
Dear Buddies,

This is my "guide to trying lithium." I wrote up this protocol for a buddy struggling at 18 months who wants to see if lithium will help.  Maybe some of you will find this useful.  Note to moderators, This is VERY prescriptive because this is what a specific buddy asked me to do.  For the record, I state below that this is what I intend to do once I have logged a few months off valium:

I found a good clean source of lithium orotate with as little else in it as possible.  This brand is pure.  It goes out of its way to say that it does not contain any of the “other things” that normal people would not feel, but we might find a trigger, like ascorbyl palmitate (Vitamin C) or calcium or magnesium in any form, etc.  When I do this, this is what I will get.  It is also a capsule which means it is powder so you can empty the capsules and weigh the powder:
https://www.amazon.com/Relentless-Improvement-High-Purity-Excipient-Formulation/dp/B07BSMQPDW/ref=sr_1_2_sspa?crid=3UV8G7W5IXAZI&keywords=lithium+orotate&qid=1571852532&sprefix=lithium%2Caps%2C139&sr=8-2-spons&psc=1&spLa=ZW5jcnlwdGVkUXVhbGlmaWVyPUEzS01VM1FUVEQwR05RJmVuY3J5cHRlZElkPUEwMTM1NjU5MzZNS0VNTEowNVdGSCZlbmNyeXB0ZWRBZElkPUEwNjQyNDc5Mk9VSjBCNTZWSTMzJndpZGdldE5hbWU9c3BfYXRmJmFjdGlvbj1jbGlja1JlZGlyZWN0JmRvTm90TG9nQ2xpY2s9dHJ1ZQ==

You will need large, empty capsules to fill:
https://www.amazon.com/PurecapsUSA-Clear-Vegetarian-Capsules-Joined/dp/B00I7DVEJS/ref=sr_1_2_sspa?keywords=empty+vegetarian+capsules&qid=1571850888&sr=8-2-spons&psc=1&spLa=ZW5jcnlwdGVkUXVhbGlmaWVyPUFDUEpGUFRJTVlINzYmZW5jcnlwdGVkSWQ9QTA2NDcxMjYzOE5CQkNIOVc2MTQ4JmVuY3J5cHRlZEFkSWQ9QTAwMDAwNDAyOFpDS1JVMzFSTFRUJndpZGdldE5hbWU9c3BfYXRmJmFjdGlvbj1jbGlja1JlZGlyZWN0JmRvTm90TG9nQ2xpY2s9dHJ1ZQ==

Tiny spoons for measuring and filling:
https://www.amazon.com/Norpro-Stainless-Measuring-Spoons-smidgen/dp/B0009X1P9S/ref=sr_1_4?crid=27YSLSSIXL2UO&keywords=measuring+spoons+smidgen+pinch+dash&qid=1571850673&sprefix=measuring+spoons+smid%2Caps%2C134&sr=8-4

And a REASONABLY accurate milligram scale
https://www.amazon.com/Smart-Weigh-GEM20-Precision-Milligram/dp/B00ESHDGOI/ref=sr_1_1_sspa?crid=1BW30LCGBPR31&keywords=gemini+milligram+scale&qid=1571851012&sprefix=gemini+mill%2Caps%2C131&sr=8-1-spons&psc=1&spLa=ZW5jcnlwdGVkUXVhbGlmaWVyPUEzRFRYSVVLSVMyNlo0JmVuY3J5cHRlZElkPUEwNjU1NzUyMVhZSk4zQVdEWERBRCZlbmNyeXB0ZWRBZElkPUEwNzMxNDUxTTNGSTYzNk1TVjNBJndpZGdldE5hbWU9c3BfYXRmJmFjdGlvbj1jbGlja1JlZGlyZWN0JmRvTm90TG9nQ2xpY2s9dHJ1ZQ==

Not sure about shipping, but all of that will cost about $60 without shipping.

Each capsule contains a certain amount of powder, but the important thing is that the powder contains 5 mg lithium.  If you get a different brand that is a tablet instead of a capsule, that is ok, but it could contain stuff we do not want, and you will need to cut the tablet into quarters.  I like capsules, so I can weigh powders, but if all you can get is tablets, then buy the scale, but do not buy the empty capsules.

If you get the lithium orotate capsules, empty 1 capsule onto the scale and see what it weighs.  If you get tabs, weigh the tabs. Do a few to get an average weight.  Then either weigh out a bunch of powder until you are get 1/4 of a capsule, and fill the empties, or cut tablets until you get a bunch of good quarter tabs.

The scale is accurate to about +/- 0.003g (+/- 3 mg), so do not worry about its being exact.  For example if the capsule content weighs about 0.200 g (200 mg) you will find it will vary from 0.180 g to 0.220 g.  That is accounting for manufacturing variation and scale accuracy. So in this example, you weigh out about 0.050 g (50 mg).  So anywhere from 0.045 to 0.055 g is acceptable.  If you have powder from capsules, you can use the tiny spoons to put that amount in the capsule.  Remember that 0.050 g or whatever a quarter capsule of POWDER (or tablet) weighs = 1.25 mg lithium.

Once you have prepared a few days wait for a day when you have nothing to do, and take one in the morning.  It might make you calm.  It might rev you up.  It might do nothing.  I want you to take it in the morning so you are awake and can feel what it does.

If it makes you calm, move the dose to night. 
If it revs you up, keep it in the morning. 
If it revs you up A LOT, halve the dose. 
If it does nothing, double the dose.

Once you feel it do SOMETHING, hold there.  Take that dose until you no longer feel it do anything.  That might be a week. That might be a month.  If it still makes you calm after a month, increase the dose until you feel just a little drowsy during the day.  Just barely.  Hold there until you no longer feel drowsy during the day.

Ideally, you don’t feel it until you get to a few milligrams of LITHIUM.  Then you keep building lithium orotate until you can take about 25 mg lithium or 5 pills.  At that point you see a psychiatrist, and get a scrip for 150 mg lithium carbonate, the lowest available dose, which equals 28 mg lithium. You never take more than that.  When you can stay on that dose for several months, you might notice significant improvement.

That is the theory.    Now here is the catch.  It looks very good, and I mean VERY good on paper.  That DOES NOT MEAN IT WILL ACTUALLY WORK AT ALL.  If I had a dollar for everything that I thought would work on paper, I would have a lot of dollars.

If anyone actually does this, please let the rest of us know.

Good luck,

[...]
(YPNRYTHIT, AIYAGTH, KG!)
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The Use of Lithium to alter glutamate reception
« Reply #16 on: November 06, 2019, 09:10:42 pm »
Following
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The Use of Lithium to alter glutamate reception
« Reply #17 on: November 06, 2019, 09:27:47 pm »
bumping too
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The Use of Lithium to alter glutamate reception
« Reply #18 on: November 07, 2019, 01:03:32 am »
Hey, [...].
Just wanted to throw my experience into this thread in case it could help.

Last year, I took a stack of supplements for about 6 months or so with the goal of boosting BDNF.
Lithium was one of said supplements. I took it in the orotate form daily for those 6 months.
I felt pretty decent while on the stack, seemed to be more alert with more energy, etc. Basic nootropic type of effects.

But it didn't cure me by any means. I had a 'setback' a few months after I stopped taking the stack and am worse than I ever have been. So... it may have helped a little while on it, but 6 months taking it was definitely not enough to repair whatever neurological damage or issue I have.
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The Use of Lithium to alter glutamate reception
« Reply #19 on: November 07, 2019, 01:42:18 am »
Maybe it’s not necessarily about time but about finding the right “medicine “. My background is in Osteopathic manual therapy. We were taught the general principle that the body has self regulating and self healing mechanisms. In cases where illness presented itself, as Osteopaths we would work through structure trying to find tissues or bones that were lacking physiological range of motion and bring motion to that structure. This would then effectively take the barrier away from healing and the body would then resume its self regulating/healing mechanism. It’s not effective and even detrimental to just throw everything at the body hoping that something sticks. The key lesion would have to be found and corrected and then miracles could occur. I understand that the brain is much more complicated than physical structure but in principle the approach and outcome should be the same.
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.