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The Use of Lithium to alter glutamate reception


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Nov,

 

Thank you for sharing.  I do think one would have to get beyond a few milligrams found in orotate to have permanent change.  I do hope it did not contribute to your setback.  Do you have any thoughts on that?

 

Definitely had nothing to do with my setback.

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Well put Colley.  We are talking about working up to a dose a bipolar person would not even feel.

 

And Why Lithium?  Because lithium has one very specific trait that makes it unique, it slows cations (positive ions) thru ion gated channels, which makes us calm, while simultaneously holding glutamate in the synapse longer.  If we can hold glutamate in the synapse longer, increasing slowly and repeatedly for 6 months to a year, we juuuuuuuuuuuust might coax some of those receptors away, and reduce current flow on a more permanent basis.  If we coax some glutamate receptors away and reduce their current, we might reverse some benzo damage.

 

Maybe.  That is the question.

 

Ramcon1

YPN,RYTHIT, AIYAGTH, KG!

 

I see. I'm sorry. I misunderstood the dosing on it.

 

You're trying to updose someone from a very low dose to the smallest dose made correct?

 

Bipolar people feel those doses still. They still have known side effects even though they're much diminished.

For a psychiatrist to prescribe the lowest dose they'll probably still require renal and TSH/T3/T4 (Thyroid) panels.

 

 

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Fayt,

 

Yes exactly what you said.  Build from orotate, or even fractions of orotate, so 1-5 mg lithium ion to the lowest dose made for carbonate which is 150 mg carbonate, 28 mg lithium ion.

 

Ramcon1

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Ramcon... Lots of questions, bare with me.

 

So, do lithium, SAMe, and Zoloft/sertraline essentially accomplish the same goal?

Or do you theorize the mechanism of one may be more promising than the others?

 

Could one use them synergistically to positive effect?

 

Are your theories on dosage and timeframe for lithium based on anything in particular, or just estimated speculation?

Orotate is the easiest to get, so you think 25mg of orotate for 6 months would do the job, yeah?

 

......

As a side thought... I really like the NO/ONOO theory because it has potential to explain why our symptoms are so varied. And each one of them seems to mimic or mirror one of the prominently proposed NO/ONOO diseases, almost perfectly. Do you really think upregulated ionotropic glutamate receptors could similarly and accurately explain ALL of the different symptoms that we have?

 

What about someone like myself who had a 'setback' from intense workouts/cardio (which I've heard from other buddies as well, like PowerMM) what could be the explained neurophysiological process for such a 'setback'? How could a workout kindle those receptors or 'poke' something as you've suggested?

 

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Nov,

 

All good questions.

 

I know that lithium ions and serotonergic meds and supps work by different mechanisms, but yes they accomplish the same goal: reduction in count, firing voltage, and current flow thru glutamate receptors, particularly NMDA.  Do I know if one will work "better" than another?  I have absolutely no idea, and I SUSPECT, have no proof, that some will respond better to one than the other.  Will they be synergistic?  I SUSPECT, I really have no way to know because no one has studied this yet, that they would be additive, as in you could get some benefit from the serotonin mechanism and additional benefit from the mechanism of lithium, but not synergistic in the truest definition of the word, as in "the whole is greater than the sum of its parts, 2+2=5."

 

My theories on time frame and dosages are "educated guesses."

 

I saw a good gastro doc.  She called herself a neurological gastroenterologist, but her neurology knowledge was not that deep.  A lot of IBS comes along with something called "visceral hypersensitivity," which is a fancy way of saying you feel your colon like a normal person feels his fingertips.  I have this.  As I said, she does not know much about neurology, but she knows, "Patient has visceral hypersensitivity.  I prescribe Zoloft.  Build from 12.5 to 50 mg and in 6 months 75% of my patients are cured."

 

I dig, and find surprise surprise, visceral hypersensitivity is conclusively correlated with NMDA hyperfunction.

 

Thus the educated guess of dose and time frame.  And keep going.  Average people who benefit from SAMe benefit from between 400 and 800 mg tops.  Another educated guess.  The lithium dose was just from googling around.  Lots of psyche journals talk about the benefits of "low dose lithium" for anxiety and depression.

Here's one article:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854802/

 

When they talk about low dose 150 mg, they mean 150 mg carbonate = 28 mg lithium ion, which equals 5 1/2 - 120 mg orotate supps.  My other educated guess is that anyone with health insurance will literally pay pennies a day for 150 mg lithium carbonate med, so that recommendation was purely financial.  There is no functional difference between one 150 mg carbonate med and 5 1/2 120mg orotate supps, so if it is easier/cheaper for you to use orotate the whole time, I cannot see a difference.

 

And the best for last:

 

Yes, I do think that glutamate receptor dysfunction could really be the cause of all of our misery.  BUT, that does NOT mean that the NO-ONOO mechanism does not come into play!  There are a dozen maybe dozens of different chemical reactions that control the count and function (voltage and current) of glutamate receptors, and I have absolutely if or how much the idea if NO-ONOO is important to that control.  I have only started skimming the NO-ONOO articles, and I have a few hundred pages of stuff I need to go thru first before I get to them.  But I remember seeing peroxynitrite (ONOO) NMDA and nanotubules on the same page somewhere in some article.  Nanotubules are essential for NMDA regulation and if we can tie NO-ONOO and peroxynitrite to the formulation of nanotubules, we have a strong argument that it is VERY important to NMDA.

 

But right now, I, ramcon1, do not know that.  Yet.

 

If you Nov3 or anyone who has read a lot on NO-ONOO want to post or PM me a link to the paper that says "HERE! LOOK HERE! PEROXYNITRITE NMDA NANOTUBULES IS IN THIS PAPER!" that would help me a lot.

 

Now I am back to work.  Today is a decent day, and I intend to use it.

 

Be well, and thanks for the great questions I hope will foster more discussion on all three threads.

 

Ramcon1

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Thanks guys - good stuff.

 

 

Ramcon1- I recommend Pall’s book - it goes into so much detail. Right now, I’m reading about NMDA in the NO OH NOO process ....

 

 

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As Power said, Pall's book is a great suggestion.

I would like to add, make sure you read LaCorte's article as well. As that is the root of this whole connection to benzos.

 

https://cdn.shopify.com/s/files/1/2161/5909/files/SL.pdf

 

Elevated activity of the NMDA receptors is a hallmark element of the NO/ONOO cycle that is mentioned by both Pall and LaCorte. LaCorte acknowledges the role of these receptors in later stages of 'withdrawal', but in either his or Pall's work, I don't believe there are specific mentions of the formation of nanotubules... None that I have seen.

 

Regardless, while excessive NMDA activity is a central part of the LaCorte/Pall's NO/ONOO cycle theory, as it is with your theory, the underlying mechanism that causes both differs greatly between the two. So the proposed solutions for rectifying each issue are totally different and I can't imagine a way to tie them together in any poetic fashion.

 

Ramcon, have you reached out to the University of Arizona team that held the Benzo Withdrawal Symposium? I have spoken to a couple different members of their team. They are super cool guys; receptive to discussion and also interested in finding solutions. Maybe you could run your idea of upregulated ionotropic glutamate receptors by them. See if they have any thoughts. They might be able to provide more guidance or criticism than our non-neurochemist-minds can.

 

Ramcon, my response as posted in the NO/ONOO thread.

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I saw a good gastro doc.  She called herself a neurological gastroenterologist, but her neurology knowledge was not that deep.  A lot of IBS comes along with something called "visceral hypersensitivity," which is a fancy way of saying you feel your colon like a normal person feels his fingertips.  I have this.  As I said, she does not know much about neurology, but she knows, "Patient has visceral hypersensitivity.  I prescribe Zoloft.  Build from 12.5 to 50 mg and in 6 months 75% of my patients are cured."

 

I dig, and find surprise surprise, visceral hypersensitivity is conclusively correlated with NMDA hyperfunction.

 

That's interesting.

Does she take the patients off of Zoloft after 6 months? .......and they remain 'cured' without taking it?

 

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No.  They stay on 50 mg Zoloft of the rest of their lives.  I do not know if that is necessary.  It might be.  You might have to keep reminding those NMDA receptors to stay away.  Then again, those are people who got IBS without ever taking a benzo, so we might not have to.

 

The answer is I do not know how it applies to us.  Yet.

 

Ramcon1 

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No.  They stay on 50 mg Zoloft of the rest of their lives.  I do not know if that is necessary.  It might be.  You might have to keep reminding those NMDA receptors to stay away.  Then again, those are people who got IBS without ever taking a benzo, so we might not have to.

 

Hm.... I wonder if she's tried to take her patients off or if that is just an assumptive decision to keep them perpetually medicated. It's a different scenario, but if they're caused by the same essential neurological pathology as you suggest and their pain comes back upon Zoloft cessation, that might be a blow to the fact that it can be 'cured', as opposed to just treated. Maybe not! As again, totally different scenario, but I would imagine our receptor imbalance would be much worse than one with just IBS. And thus, harder to address?... That said, I would gladly stay on a medication indefinitely if it alleviated my symptoms.

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I posted about this drug in another forum. It's related to Buspar.

 

https://en.wikipedia.org/wiki/Tandospirone#Research

 

"In February 2018, a study was conducted by researchers at the Queensland University of Technology and published in the journal Scientific Reports. Researchers found that tandospirone helped reverse brain deficits caused by chronic alcohol exposure in mice. The study was the first of its kind and brought interest in the drug for possible treatment of alcohol withdrawal symptoms."

 

 

I've been trying to get my hands on some but I have to order it at a crazy expensive rate from Japan or in bulk wholesale from China. There's no middle ground  :laugh:

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Nov,

 

I am going to post this on the SAMe/serotonin thread where it is most relevant, but this is the first article I found that got me digging way deeper into serotonin before I even met the gastro doc:

 

http://birthfaith.org/nutrition/glutamate-and-anxiety

 

She is her own case study, and clearly plans on staying on Zoloft for the rest of her life.  Some say she will one day "pay the piper," because Zoloft will eventually stop working and hurt her like benzos hurt us.  I disagree, but I have no proof.  My dad has been on Zoloft for at least 12 years, and he is 89 and healthy.

 

Fayt,

If I had seen your post 3 years ago, I would have said, "Maybe taper K before quitting smoking."  Now having quit smoking and still on Valium, I think you made the right choice to quit smoking first.  Probably time to taper K tho.  Maybe cross to V when you get to 2 mg.

Do what you must to survive.

 

Ramcon1

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I posted about this drug in another forum. It's related to Buspar.

 

https://en.wikipedia.org/wiki/Tandospirone#Research

 

"In February 2018, a study was conducted by researchers at the Queensland University of Technology and published in the journal Scientific Reports. Researchers found that tandospirone helped reverse brain deficits caused by chronic alcohol exposure in mice. The study was the first of its kind and brought interest in the drug for possible treatment of alcohol withdrawal symptoms."

 

'...we show that long-term DID elicits profound deficits in neurogenesis and neuronal fate specification in the dorsal hippocampus that are entirely reversed by a 2-week chronic treatment with the 5-HT1A partial agonist tandospirone'

 

Though the issue addressed seems to be different here, being that it is related to 5-HT1A, not NMDA, it's cool to see the damage 'entirely reversed'. Though, what is a '2-week chronic' treatment? Lol.

 

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Nov,

 

They are absolutely related.  I am 90% sure (note, NOT 100%, and not even 99, but 90%) that the reason ANY serotonergic med, Zoloft/sertraline or tandospirone has anxiolytic effects is BECAUSE 5HT1A wears down NMDA in count, voltage and current. I have posted that paper a bunch of times, and am gathering more info on that every week.

 

ramcon1

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Ramcon as someone who has had head pressure and vibrating brain for years. I took cipralex and it just made my head pressure 100 worse (assuming head pressure is related to glutamate in some way) and sent me into a deep depression/anxiety state. Why didn’t this work for me?
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They are absolutely related.  I am 90% sure (note, NOT 100%, and not even 99, but 90%) that the reason ANY serotonergic med, Zoloft/sertraline or tandospirone has anxiolytic effects is BECAUSE 5HT1A wears down NMDA in count, voltage and current. I have posted that paper a bunch of times, and am gathering more info on that every week.

 

Oh, okay. I understand the thought process now. Interesting!

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Greek,

 

I am not a doctor, but I will give you a very good educated guess.

 

Assuming you were 6 months off benzos when you gave the SSRI a try so it would have a chance, it made you worse because your doctor gave you a dose as if you were a neurotypical person.  The serotonin receptors are right next to those glutamate receptors, and they inhibit the transport of glutamate out of the synapse, so you got slammed by the extra glutamate.  That is why I said if I do it, it will have to be homeopathically, literally starting at a few milligrams, and increasing a few milligrams at a time (after I am 6 months off benzos), because I am SURE that all my system could bear!  And I am 99% sure I am going to try Lithium and SAMe before Zoloft.

 

Ramcon1

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I wasn’t on any medication before taking the SSRI. I actually started at half of the lowest dose at 2.5 mg. When I went up to 5mg after three weeks of being on this dose. Within a week of being on 5 mg all of a sudden, the medication turned on me. I find it interesting because this would usually happen to someone in withdrawal. The common consensus here is that adding an SSRI during withdrawal is like adding gasoline to a fire. I guess that the original condition I had had my nervous system extremely sensitized, so that even a small dose of SSRI put me over the edge. Just be careful
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Greek,

 

I agree with everything you said about an SSRI in benzo wd.  I think, but cannot prove, that many people have too many glutamate receptors for other reasons.  Maybe we were born that way.  I think I was.  I think that is why I was born with insomnia, and I was never healthier than when Ativan was working well.  Then it made my condition worse, and here I am.  If an SSRI did that to you, it is possible that you also had too many glutamate receptors pre-benzo.  What we both need is to be put into a medically induced coma and bombarded with with either a serotonegeric med or supp, or just pure glutamate until we scare those receptors away!  :D

 

Or maybe lithium is a better choice for us?  I honestly do not know.  Yet.

 

Ramcon1

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Fayt,

If I had seen your post 3 years ago, I would have said, "Maybe taper K before quitting smoking."  Now having quit smoking and still on Valium, I think you made the right choice to quit smoking first.  Probably time to taper K tho.  Maybe cross to V when you get to 2 mg.

Do what you must to survive.

 

Thanks, but I'm in no rush.

 

K acts quite long in my body. I've taken it once a day for so many years that I tolerate it pretty well.

Pretty sure I can drop back to 2mg without too much issue. I haven't been at this higher dose too long.

 

I had to ask if nicotine was causing me MORE anxiety or less on average. It definite decreased my anxiety

on demand, which was great. But overall I think it left me in a high state of anxiety.

 

So I quit... ~25 days ago.

 

I've quit before. I wasn't a heavy smoker. I kinda enjoyed it more than anything. I like a few of the properties

of nicotine. It acts to suppress noise in the brain. It's a phenomena called Sensory Gating that isn't terribly well

understood. I haven't had to attend any parties in the last month but I doubt I would handle them well without

nicotine.

 

Sensory gating is the reason nicotine is incredibly helpful to people with autism and a number of other mental

disorders where the "noise" of the world is a little too loud. It's thought to be the reason people with BPD and

Schizophrena are most commonly smokers.

 

 

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Random thought, but it is strange to me that benzos could cause such stubborn, long-lasting upregulation of glutamate receptors, but only for a small percentage of people.

Why do such a small percentage of users suffer horrible, long term effects, while others' receptors have no issue returning back to homeostasis virtually immediately?

 

I began getting symptoms within a few months of infrequent benzo use. Then, after my CT 2+ years ago, it has literally gotten worse with each month that passes. If most people's receptors gradually heal within a couple weeks/months, why would some have receptors that get perpetually worse over time and last indefinitely? And how could some users have irrevocable upregulation after a few months of use, while others get none after using higher doses for a decade? We are talking about receptors that should generally be functioning the same way, minus some identifiable, undetermined pathophysiology that separates some people's receptors from others.

 

I don't know, just sounds strange to me that upregulation could be the singular purported pathophysiology. There would have to be something additional in my opinion. I don't mean to once again contrast this theory with NO/ONOO-, but just for the sake of explaining my point... With that theory, it's not necessarily the benzo itself causing the specific pathophysiology, but the benzos initiating an independent pathophysiology that only really detrimentally affects people on a long term basis that are genetically or biologically susceptible to this process... At that point, the self perpetuating chemical process becomes the issue; not any up/downregulation that the benzos may have caused...

 

In my eyes, this is a sound explanation of how a month-long user might still get symptoms a decade later while a decade long user might only have 'withdrawal' symptoms for a month. The discrepancy for healing timeframes does not seem to add up if the issue is merely receptor dysregulation. Again, not everyones' receptors 'remember' and 'return' to that state perpetually. Why would some? I have not heard of similar examples of such drastic receptor responses to the same stimuli. Has anyone read proven, studied accounts of a rare, severe, substance-induced chronic upregulation of any type of brain receptor? Do we have any similar phenomena to make logical comparisons? The NO/ONOO theory may not be 100% proven fact to some, though there's a lot of data adding up in its favor, but it provides models of comparison that do add up and make sense; various parallels to other diseases and disorders AND a perfect explanation about the aforementioned discrepancies and drastically different responses.

 

Not trying to shift the topic on ya Ramcon, just trying to offer an example to further explain my thought process and point! Hope this makes sense. If I am missing something please do let me know!!

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