The Use of Lithium to alter glutamate reception

Good questions. I think if we knew we would be able to decipher mental illness in general. I think about this all the time. For example, a normal person becomes depressed but is able to go back to normal baseline after a while. How does the brain accomplish this? What mechanisms are in place to bring that person out of their temporary depression and back to a normal baseline? Another question I have is why time plays such a big factor. When it comes to other injuries in the body, it make more sense that time would be a factor. There’s a lot of work to be done; bring nutrients and material to help rebuild tissue/bone etc. How much work can tiny little receptors need to upregulate? How does the brain/mind maintain its integrity? We know how to strengthen the body but how do we strengthen the brain/mind?

All I will say is if you think the long term side effects of benzos are bad, you should see the long term side effects of lithium. I think it's a pretty risky strategy.

 

Very Common (> 10% incidence) adverse effects of lithium include

Confusion

Constipation (usually transient, but can persist in some)

Decreased memory

Diarrhea (usually transient, but can persist in some)

Dry mouth

EKG changes — usually benign changes in T waves.

Hand tremor (usually transient, but can persist in some)

Headache

Hyperreflexia — overresponsive reflexes.

Leukocytosis — elevated white blood cell count

Muscle weakness (usually transient, but can persist in some)

Myoclonus — muscle twitching.

Nausea (usually transient, but can persist in some)

Polydypsia — increased thirst.

Polyuria — increased urination.

Renal (kidney) toxicity which may lead to chronic kidney failure

Vomiting (usually transient, but can persist in some)

Vertigo

Weight gain

Common (1–10%) adverse effects include

Acne

Extrapyramidal side effects — movement-related problems such as muscle rigidity, parkinsonism, dystonia, etc.

Euthyroid goitre — i.e. the formation of a goitre despite normal thyroid functioning.

Hypothyroidism — a deficiency of thyroid hormone.

Hair loss/hair thinning

I took a tiny dose of lithium orotate for two weeks, 2.5 milligrams. It did not help me at all. I'm wondering how long it would take for this to build up in the system and actually help if it were able to.

First Greek,

 

You are so right.  It does not take a long time and energy to rebuild GABA receptors.  That is why ours is a disease of glutamate.  After a few months, it is not about not enough GABA receptors, it is about too many glutamate receptors.  Of that I am 100% certain  I am 99% certain that can take a very long time because the need to down regulate glutamate reception does not exist in nature, at least I have not been able to find it.  I cannot be 100% certain of that because just because I can't find something certainly does not mean it does not exist.

 

Data and all who fear Lithium,

 

I am NOT saying I am anywhere close certain it will actually work.  We will never know until we try, but remember, anything can be poison depending on the dose.  Lithium can be very dangerous for those who need to take it at levels used to treat bipolar disorder.  We are talking about working up from the supplement to the LOWEST prescribable dose.  I cannot say with 100% certainty that the lowest prescribable dose is safe for absolutely everyone, but it is very likely to be safe for almost everyone.

 

and Boom,

 

My best educated guess based on the references in the paper is for us to have it effect the change we need neurological restructuring, it would take at least a few months at 25-28 mg Li+ ion.  (600 mg orotate supp or 150 mg carbonate med.) Do not let the 600 mg part scare you.  Remember the chart that I posted in the beginning of this thread 120 mg orotate = 5 mg Li+.  150 mg carbonate = 28 mg Li+

 

Hope that helped.

 

Ramcon1

Question about lithium. Since it acts as a mood stabilizer wouldn’t it also cause a flattening effect on the emotions like a lot of antidepressants or antipsychotics do? I’ve seen YouTube videos of people suffering with bipolar complaining of this effect.

Sorry, one more question. If the down regulation of glutamate is a problem then how do we explain windows? As a side note I’m a smoker. Many years ago I decided to quit. I had head pressure that increased every day to a point where on the 4th day I felt like my head was going to explode. This feeling of head pressure, irritability, rumination came to climax and then just stoped. It was as if my mind opened up and all the symptoms went away just like that. Was that pressure I was feeling in my head at the time glutamate related?

Question about lithium. Since it acts as a mood stabilizer wouldn’t it also cause a flattening effect on the emotions like a lot of antidepressants or antipsychotics do? I’ve seen YouTube videos of people suffering with bipolar complaining of this effect.

 

Yes  Greek,

Im not bipolar however it did that to me ( the  Lithium supplement)

and some of the other side effects mentioned in a post by Data guy,

much like the valium did for me also sadly

and I was never able to tolerate either

and tried the lithium orotate  several times

for varying lengths and altered doses.

  Just wasnt for me.

 

Flattening/dumbed down/ and a nothingness for me, confusion, etc etc

which was way worse than windows and waves

that happen in this healing journey.

Greek,

 

Windows are when, by pure random chance or by conscious choice, you have lowered your pool of glutamate in your blood, it diffused out of your nerves, so there was less glutamate to be received.  Now, during what is hopefully my final taper after reinstatement, the only way I can function, is to eat absolutely no free glutamate and no histamine liberators.

 

I eat no dairy, no grains, no vegetables.  I eat the same 7 carefully selected home-prepared and minimally processed foods every night in one meal at about 10 pm.  If I try to eat earlier, I ruin the day.  The act of eating releases glutamate and histamine.  If I eat anything else, I can ruin a week. This life style sucks ass, but I have gotten used to it.  It is better to do this than be hysterical, which is what happens when I don't. 

 

Another thing that can cause a window is stress.  When you have a stressful day, you create adrenaline to get through it.  Adrenaline speeds glutamate out if the synapase, and the next day violá, a window.

 

Ah smoking my favorite/least favorite subject.  I had to quit because of IBS.  I miss it everyday.  There are two camps on this one:

Camp 1:  Benzo wd is very hard.  Just keep smoking until you are a year over it.

Camp 2:  Tobacco, while giving a glutamate boost, is a strong accelerator of glutamate transport, so it takes glutamate out of the synapse quicker.  Anything that takes glutamate out of the synapse quicker will slow or even prevent healing.

 

I will borrow from Sky, "we are all so different."

 

I tell you when I am 100% certain of something, and if I do, I promise you on whatever God to whom you pray, you can accept that and move on.  On smoking, I have absolutely no idea and I have to agree with Sky, everyone is going to be different.  Some will heal better smoking.  Some will never heal until they quit.  Some it does not matter.  I have read success stories with all three.

 

The head pressure could have been glutamate, but more probably histamine.  Tobacco is also an antihistamine.

 

As for flattening, its possible.  I put in my "how I am going to do it when I am clean" post, if it is "sedating," take it all at bedtime.  Last time I tried it it revved me up.  Frankly sedating is the best thing that could happen to me, and flattening would not be the end of the world either.  If it meant I could eat?

I would take "flattening" in a second.  That is pure opinion.

 

Whenever I am ready, at least based on my current knowledge, I am going to try a few mgs of lithium for a week and see what it does.  Then I will try a few mgs of SAMe for a week and see what that does.  It may be a combination that achieves the effect we want.

 

Also and finally, that is my plan based on what I know now.  I have thousands of pages of reading to do between now and getting clean, and I may change my mind.  I am also looking to see how any of you who are already clean do with various things you try, and hope to learn from your experience.

 

Hope that helped.

 

Ramcon1

Ramcon,

Any thoughts on my questions?

 

Greek,

Agreed, that is all very interesting.

Another interesting note, Pall theorizes that PTSD is also a NO/ONOO cycle disorder.

So some sort of extreme event or recurrent psychological stressor or trauma can instigate a recurrent cycle of depression or mental illness. So again, not caused by receptor changes inherently, but a cyclical inflammation response of sorts... It's hard to create blanket statements about mental illness though of course. When I think of my own history with anxiety and depression, it certainly didn't just appear. It was on account of recurrent psychological trauma or life stresses. Stressful situation after stressful situation after stressful situation. If I was isolated in a remote, beautiful forest and allowed to do things I love all day every day, there is no way my mental health issues would've emerged. I may have been predisposed toward falling into the mental health rabbit hole, but could've only fallen victim with the stressors, triggers, and instigators.

 

Maybe some people just become depressed from nothing. Without constant stress, without trauma, without cyclical negative thoughts. I dunno! Again, can't make blanket statements. But I'd guess that a considerable amount of depressed people weren't simply super positive, stress-free, happy-go-lucky people that all the sudden got hit with inexplainable chronic depression after a day of natural sadness. Repeated stress is known to cause inflammation and disease, and not just in the brain. Constant stress is the killer, imo. And once it hits enough, it could create a cyclical, inflammatory response, a la NO/ONOO. But, that's just another theory or different explanation...........could be the receptors, who knows!

read the Ashton manual supplement

 

https://www.benzo.org.uk/ashsupp11.htm

https://neuro.psychiatryonline.org/doi/full/10.1176/jnp.12.3.328

 

'Sensitization Phenomena in Psychiatric Illness: Lessons from the Kindling Model'

 

There's a lot to digest here, but it's all about glutamate receptor kindling and the resulting hypersensitivity.

 

Is it possible that our glutamate-receptor issue isn't necessarily that we have too many, but the one's that we do have are kindled, hypersensitive, and dysfunctional? Could it be that simple? The article talks about alcohol withdrawal and kindling and how when the glutamate receptors are kindled, they remain hypersensitive for life; permanently dysfunctional. Each withdrawal or subsequent response to the stimuli is worse than the last. Could it be that we simply have kindled glutamate receptors and whenever some external or internal stimuli affects those receptors too much, it throws us back into that withdrawal state - and a worse one than the prior at that?

 

This is not a fun idea to entertain. As, I don't know how one would address kindled, dysfunctional receptors. It seems to be a concept that has been pretty accepted for a while though, this article is from a decade ago. And I've not seen anything written about successfully repairing kindled, hypersensitive receptors. The common consensus seems to be that the damage is permanent. Again, the article talks about this state of dysfunction in relation to alcohol withdrawal, but it's not a stretch to connect the dots to benzos? ....Correct me if I'm wrong, but kindled hypersensitive receptors and an excess of glutamate receptors as theorized in this thread are totally different neurological beasts, yeah? I don't imagine lithium or anything else could completely remove all of our damaged glutamate receptors.

 

Though, maybe it isn't 'simple' in that, I don't think the exact molecular mechanisms for a 'kindled state' are totally and completely elucidated. WHY are the receptors in a state of hyperexcitability? There was some discussion of this specific pathophysiology in the article, maybe it explained it all perfectly, but I didn't gather that. But I am also not a neuroscientist and am dead tired and in a wave. Regardless, I think it says some potentially important things and poses new questions for this thread.

Nov3 (and All),

 

I am having a bad day, but I cannot just leave this out there.  It is too important.  Before I give you a short answer to what may be the best question asked yet, am going to ask in advance that nobody panic.

 

I only gave the article the skimming my brain would allow today.  It was not a bad skimming.  It was far from thorough, but the short answer to your question is:

 

I think this is exactly what is wrong with us.  Exactly. 

 

They only partially cover the mechanism of kindling, and again, I only partially read the authors discussion.  But it is my opinion that dysfunctional glutamate receptors are THE SOURCE of our misery, and upregulation is a known part of kindling.  And kindling is THE REASON a member was well for "x" months/years and then did "something," an antibiotic, quit smoking, started smoking, has no idea at all what he did, but whatever he did it induced a voltage on those ionotropic glutamate receptors, he kindled, and he was sick all over again.

 

This is why I think a treatment, something like a lithium, zoloft, whatever, is essential for our recovery.  We need to beat those ionotropic glutamate subunits into submission at the neurobiological level, or we will be sick for a very, very long time.

 

All cards on the table, I cannot know this for certain, but I believe it in my bones, and it is my goal in life to understand and fix this exact problem.

 

There are other schools of thought on this:

After 6-8 years you are finally done, your glutamate receptors are fully healed and life goes on.

Kindling of ionotropic glutamate receptors only happens to a small percentage of those who become dependent on glutamate modulating meds or drugs, so don't worry.

Live like a monk till you die, and you will be fine, but if you don't you will be fucked.

 

I am not willing to accept those schools, because if I do, I will lose all hope and purpose.  It is my goal in life to understand and fix this exact problem.

 

Good find.  I will read it again and again when my mind is more clear, but, I think this is THE defining moment of these research threads.

 

Please don't panic.  It does not help. Hang in there.  Do the best you can with today, and worry about tomorrow when it gets here.

 

And.

 

If you are 2 years clean, and life sucks, and/or you sound like what I described as "kindled,"  I am not a doctor, etc and so forth, but when I am clean I will definitely try some of the ideas batted around in Chewing the Fat.

 

Ramcon1

If this is indeed the problem, here is another potential solution.

 

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0224834

 

'Deep brain stimulation restores the glutamatergic and GABAergic synaptic transmission and plasticity to normal levels in kindled rats'

 

Published just 10 days ago...

Thanks Ramcon1,

 

You are making a positive difference. All of us that are searching and pushing forward are.

 

 

We have so much more in the way of resources available to us today compared to years previous.

 

As long as we keep asking, searching, and pushing, it’s possible to find a “cure”.

 

That same process is what led to solving problems of the past - smallpox, measles, malaria, polio, etc.

 

 

Good stuff Nov3!

 

 

 

 

 

 

Nov,

 

Holy $hit.  Good find again. 

 

I am in a bad wave and having a really, really tough time right now.  I might be sick for a week.I will not abandon this.  I have book marked the last two links you sent, and have moved them to the top of the reading list.

 

I will also move all of this to another thread.  You guys keep poking.  I will be back when I feel I can get my head.

 

You all do me a favor and take the discussion of kindling and Deep Brain Stimulation to that thread.

 

Ok?

 

Ramcon1

 

Ramcon1

Ramcom, can you speak to how something like Lamictal, which works on Ca channels and decreases glutamate release, would fit into your theory?

There are other schools of thought on this:

 

After 6-8 years you are finally done, your glutamate receptors are fully healed and life goes on.

 

Kindling of ionotropic glutamate receptors only happens to a small percentage of those who become dependent on glutamate modulating meds or drugs, so don't worry.

 

Live like a monk till you die, and you will be fine, but if you don't you will be fucked.

 

I am not willing to accept those schools, because if I do, I will lose all hope and purpose.  It is my goal in life to understand and fix this exact problem.

 

Yeah uhh.. Maybe you should consider the other "schools". To outright reject other schools of thought is pretty

dogmatic to your own belief.

 

I fear you fail to see that everyone takes benzos for different reasoning. One person's true problem may be entirely

different than another. Some people here's life slipped up and they ended up on Ativan. Some people here are actually

psychotic. I think you have to differentiate those two and realize they're two different animals entirely.

 

To try and treat everyone under one way of thinking doesn't make any sense.

 

It's most likely that your receptors go back to a relative normal. Who knows if they're permanently a little screwed. Some

people report them being perfect. Others don't. So obviously we have more than one boat. There are probably a dozen boats

some of which we don't even know about.

 

That desire to know. To know exactly. That's our ego. Sometimes you just have to recognize the boat your in and learn to

navigate the waters with the boat you understand.

 

Fayt

Update on my Lithium Orotate and SAM-E trial.

 

So I've been taking 5mg of LO (some days at 10mg) and 400mg of SAM-E for approx 4-6 weeks. Initially there was some benefit; less head pressure / pain and better emotional control. However this has been hit and miss. Therefore very difficult to tie to this protocol and possibly easier to tie to the windows and waves theory.

 

I've kept up on the protocol and have just moved my SAM-E to 600mg / day. This is making my head pressure worse for the moment; seems like when I take more SAM-E, the first couple of hours are increased headache / pressure symptoms. Unfortunately my mood has been terrible these last couple of weeks. Bad days of dark depression... not much anxiety though. I'm sure my symptoms (headaches / pressure / tinnnitus) is driving the depression.. but who knows.

 

So, I don't believe this protocol is working in the short term. Could it work in the long term? I'm not sure... I'm reluctant to increase the SAM-E dosage any further. The Lithium Orotate I could probably manage at 10mg but I feel like it's making me calmer in a disconnected sort of way.... so I'm reluctant to hold my dosage any higher than 5mg.

 

Anyway... was really hoping this would work / help in a shorter time frame but I'll continue with this until I don't.

 

[edit] also wanted to add that I'm still taking a nicotine supplement (nicorette spray)... I've been trying to wean off of it but that's not going so well. I'm not sure how much this is affecting my benzo withdrawal and associated symptoms. It certainly can't be good for me but I believe it's better than smoking and there don't seem to be any alternatives other than another product that dumps nicotine into your body.

 

[edit] 600mg was far too much SAM-E. I've switched brands and will be sticking to 400mg (200mg 2x / day). LO I'm keeping at 5mg. Other supps included D3 1000iu, K2, EMP Power Stix multi vit and mineral, B12, Probiotics, and a vit B complex 3x per weeek.

 

take care all,

Has anyone here started the protocol as Ramcon outlined? Also Ramcon do you have any studies I could read on antidepressants reducing NMDA? My psych has been trying to give me prozac for a while

Guys I admit I do not get the science to this, altho I pop in now and then to see what some of you say

 

Question, tho, here the drs. almost always try gabapentin and/or doxepin to help people off.  Does that make sense?

Some use lyrica but of course that more expensive, tho have heard fewer side effects.

Finally, some use Depakeen (sp)?

 

According to your theories which if any make sense.  Doxepin is AD but not the others...

 

thx.

Hey guys,

 

Sorry I have been gone for a while.  I have both been busy and in a wave.  I also need to stay focussed, so I am as a rule only going to check in once a week or so.  So if you need neroscience explained, send me a PM.

 

First luket,

 

Your question is more appropriate on the SAMe-serotonin thread, but since you asked it here I will answer it here.

 

Here you go:

https://www.jneurosci.org/content/jneuro/25/23/5488.full.pdf

On paper, it looks good.  Of course if I had a nickel for everything that looked good on paper, I would have a mountain of nickels, but I would (and may once my taper is over) choose Zoloft/sertraline instead of Prozac/fluoxetine because sertraline is available as a liquid, and can be increased VERY slowly using a diabetic syringe.  If you choose to do this, you need to do algebra, so if you need help with algebra send me a PM.

 

Barbara,

 

The policy of BB is not to prescribe anything.  So just like above, "if I were you. . . " gabapentin and especially lyrica/pregabalin are poor choices for us.  They MIGHT make you feel better for a while, but they are the closest thing to reinstating on a benzo you can get, except maybe alcohol.

 

Doxepin is another story.  My sleep has been extra poor of late, and I have been looking at things to help.  I have been on Remeron/mirtazapine too long and I think it has petered out, so I am looking at alternatives, and doxepin made the top 2.

 

Here is just a little basic neuroscience:  Serotonin can help reduce NMDA action but it does this by poking NMDA so it can make you feel a bit worse, before you feel better.  I had a supply of Zyprexa/olanzapine to use when I get hysterical.  It is a powerful antihistamine, and very sedating.  I thought it might be a good sleep aid, but it pokes serotonin so it is calming, but also mildly stimulating, so it was a poor choice as a sleep aid for me.  Myself and others have had the same issue with Seroquel/quetiapine, although some find it helpful.  Neither touch GABA or INHIBIT glutamate, so will not interfere with healing.

 

Silenor/Doxepin is a tricyclic AD with a pretty good receptor profile for sleep.  Lots of antihistamine, moderate anti-adrenergic anti-acetyl-cholinergic, but it has some moderate serotonergic action as well.  So it will poke those NMDA and rev me up a bit.  But again, some find it helpful.

Next on my personal list is a different tricyclic AD Surmontil/trimipramine.  That has a very similar receptor profile to doxepin, but far less serotonergic activity.  It will not “help” me heal as in remodel my receptors, but it may “help” me heal as more often than not I am exhausted from poor sleep. I am going to try it next week.

 

So if you can tolerate them, Seroquel/quetiapine or Silenor/doxepin might have a positive effect of restructuring glutamate receptors, but beware they could rev you up if you are sensitive.

 

I will report back on Surmontil/trimipramine

 

Hope that helped.

 

“See” you next week.

 

Ramcon1

 

Hey Ramcon,

 

Sorry to hear you have been in a wave recently. The lithium idea looks promising, and the idea of downregulating glutamate seems like a worthwhile pursuit. With that being said, I came across a journal article (https://sci-hub.tw/https://doi.org/10.1111/j.1600-0773.1988.tb01856.x) which finds that chronic lithium administration (4 weeks) reduces GABA receptors in the frontal cortex. I know that we are primarily focused on downregulating NMDA, but would it not be counterproductive to downregulate GABA receptors simultaneously?

Luket,

 

I just happened to come by to check out this thread.  I am going to post that I have a boatload of additional reading to do, and if anyone here needs me to look at something, please send me a PM.

 

That paper was written in 1987.  So it is old.  It is also poorly written.  On one hand I was surprised that after doing some stoichiometry (molar-mass calculations) they did use the equivalent of approximately our target dose of 25-28 mg elemental lithium in a 150 lb human (+/1 appx 25%) they did show a reduction of only 15-20% of GABA receptors in only one specific area of the brain, the prefrontal cortex (the part of the brain that does the most "thinking.")  They went on to say that it had no effect on the hippocampus (limbic/emotional memories) and also the rest of the cortex, but the table shows other wise.  The table showed an 18% reduction in the hippocampus, a 14% reduction in the cortex, and a 2% increase in the hippocampus.

 

I am not sure if any of that matters to us, and I mean that literally.  I am not sure.  I think that GABA grows easily, and NMDA recedes slowly, and that is the reason for protraction.  Because the paper showed no decrease in the hippocampus, and misstated its effect of the occipital cortex, I personally am not going worry about it too much.

 

Still, remember, lithium is tricky.  It holds glutamate in the synapse longer so should be stimulating, and this is how it can downregulate NMDA count and function, but also slows the flow of calcium thru the NMDA pore so it is calming.  If 100 people take it, they will have 50 different levels of stimulation versus sedation.  That is why we have to play with microdoses, and see how it "feels."

 

Good luck, and remember to PM me if you need me.

 

Hope that helped,

 

Ramcon1

Alright I think I'm going to give this a shot. I am still in the process of weighing up the pros and cons but I I'm leaning more on the side of trying it at the moment. I have 5 bottles of lithium orotate from Swanson which was recommended by consumerlab as having the stated amount of lithium in it. My only apprehension is it contains magnesium stearate and silica and earlier in the thread ramcon recommended a bran that did not contain any magnesium or other additives. Should I just wait and order ramcon's recomended brand, or am I ok to get started with Swanson brand which contains magnesium stearate and silica?