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Memantine Cured Me.. But Why?

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#31 crazepharmacist

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Posted 01 June 2015 - 07:33 PM

So Ceretropic actually tested TLR's memantine a few months ago and got a 97.4% match to their reference model. That's good enough for me to buy a sample and test it.


https://www.reddit.c...esting_results/

Edited by crazepharmacist, 01 June 2015 - 07:43 PM.


#32 Kingsley

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Posted 04 June 2015 - 05:35 PM

Almosteasy:

 

Fascinating post.  Please, please keep us updated on the progress of your treatment with memantine and any tips you may have in effectively using this med.

 

This topic is of great interest to me as I have spent the last couple of years trying to find an effective treatment for my own version of cognitive dysfunction.  I am diagnosed ADHD-Inattentive type, though I have never felt that this disorder fully describes my symptoms.  The references to negative symptoms of schizophrenia in this and other threads really resonate with me as I experience every single one of them: cognitive slowness, poor memory, asociality, flat affect, thought poverty, the list goes on.  To my knowledge I have never experienced anything resembling a hallucination or delusion, but the negative schizo symptoms are intriguing to me and suggest that my symptoms may be somehow related to NMDA receptor hypo-function.

 

I currently take Vyvanse, without which I couldn't imagine getting through my work days, but it doesn't get me where I need to be cognitively.  I have tried a whole host of other supplements, vitamins, and medications which I will not list yet since I don't want to hijack your thread with too much info.  I have had some significant successes though they rarely last and are sometimes inconsistent.  I actually have some memantine laying around from a while back that I never tried.  Basically, I chickened out because I became convinced that my problem is related to NMDA receptor hypo-function, so I figured that an NMDA antagonist is the last thing I need.  However, your thread and some others scattered around the internet have convinced me to give memantine a try.  I will begin in the coming days.

 

Your success with memantine is fantastic and it's great that you are trying to figure out why it is so effective for you.  Here is a thought based on my lay understanding of some studies I have read. 

 

There are studies out there showing that memantine can be effective not just as an alzheimers treatment, but as an add-on treatment for the negative symptoms of schizophrenia.  I am new to the forum and it won't let me link to studies, but they are easily googlable.  In one of the alzherimers studies, the authors speculated as to why memantine would improve cognition in patients when, as an NMDA antagonist, it should be expected to worsen cognition.  The authors noted that memantine specifically targets a subset of NMDA receptors, the NR1/2C and NR1/2D, and leaves untouched the primary subset: NR1/2A and NR1/2B.  The authors speculated that the 2C and 2D receptors might be more highly expressed on inhibitory neurons (or something like that) such that antagonizing them may have an excitory effect.  So, could it be that your condition is related to NMDA hypo-function which memantine is paradoxically reversing by antagonizing inhibitory receptors?  Any commentary by anyone with knowledge in this area (which is not me) would be great.

 

On the other hand, ketamine has been shown to be similarly selective and it certainly doesn't improve cognition (can provide study on request, can't link it).  Who knows what the hell is going on. 

 

As to your memantine treatment, how long before you felt effects and at what dosage?  Have the effects lessened at all?  Was there cognitive impairment at first?

 

Please keep us posted!

 

 

 

 

 



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#33 AlmostEasy

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Posted 08 June 2015 - 11:56 PM

So Ceretropic actually tested TLR's memantine a few months ago and got a 97.4% match to their reference model. That's good enough for me to buy a sample and test it.


https://www.reddit.c...esting_results/

I noticed that as well but it feels a bit sketchy to trust not only that the other 2.6% of the product is harmless but that this time it's actually going to be what it was before.  Do let us know how your experience goes though, if enough validation comes in I might consider it.

 

Almosteasy:

 

Fascinating post.  Please, please keep us updated on the progress of your treatment with memantine and any tips you may have in effectively using this med.

 

This topic is of great interest to me as I have spent the last couple of years trying to find an effective treatment for my own version of cognitive dysfunction.  I am diagnosed ADHD-Inattentive type, though I have never felt that this disorder fully describes my symptoms.  The references to negative symptoms of schizophrenia in this and other threads really resonate with me as I experience every single one of them: cognitive slowness, poor memory, asociality, flat affect, thought poverty, the list goes on.  To my knowledge I have never experienced anything resembling a hallucination or delusion, but the negative schizo symptoms are intriguing to me and suggest that my symptoms may be somehow related to NMDA receptor hypo-function.

 

I currently take Vyvanse, without which I couldn't imagine getting through my work days, but it doesn't get me where I need to be cognitively.  I have tried a whole host of other supplements, vitamins, and medications which I will not list yet since I don't want to hijack your thread with too much info.  I have had some significant successes though they rarely last and are sometimes inconsistent.  I actually have some memantine laying around from a while back that I never tried.  Basically, I chickened out because I became convinced that my problem is related to NMDA receptor hypo-function, so I figured that an NMDA antagonist is the last thing I need.  However, your thread and some others scattered around the internet have convinced me to give memantine a try.  I will begin in the coming days.

 

Your success with memantine is fantastic and it's great that you are trying to figure out why it is so effective for you.  Here is a thought based on my lay understanding of some studies I have read. 

 

There are studies out there showing that memantine can be effective not just as an alzheimers treatment, but as an add-on treatment for the negative symptoms of schizophrenia.  I am new to the forum and it won't let me link to studies, but they are easily googlable.  In one of the alzherimers studies, the authors speculated as to why memantine would improve cognition in patients when, as an NMDA antagonist, it should be expected to worsen cognition.  The authors noted that memantine specifically targets a subset of NMDA receptors, the NR1/2C and NR1/2D, and leaves untouched the primary subset: NR1/2A and NR1/2B.  The authors speculated that the 2C and 2D receptors might be more highly expressed on inhibitory neurons (or something like that) such that antagonizing them may have an excitory effect.  So, could it be that your condition is related to NMDA hypo-function which memantine is paradoxically reversing by antagonizing inhibitory receptors?  Any commentary by anyone with knowledge in this area (which is not me) would be great.

 

On the other hand, ketamine has been shown to be similarly selective and it certainly doesn't improve cognition (can provide study on request, can't link it).  Who knows what the hell is going on. 

 

As to your memantine treatment, how long before you felt effects and at what dosage?  Have the effects lessened at all?  Was there cognitive impairment at first?

 

Please keep us posted!

 

First off, best of luck to you with memantine.  It's definitely a game changer for me.  I feel like damage has been done and I don't know if it can be fixed but I feel like the progression of whatever I have will probably slow and my every day experience of life is greatly increased.  It's not perfect and it's a rollercoaster every day but after 7 years of IMPENETRABLE STEEL like brain fog and cognitive impairment, memantine has finally managed to nudge me into a better place.

 

Anyways, not much time for a full post but I did want to mention a few things.  Today I accidentally took wayyyy too much.  In the morning I took 20 mg as normal out of my Ceretropic dropper then I, in a rush, accidentally took 20 mg again for my second dose instead of my normal 5mg - 10mg.  Looked at the lines wrong and didn't realize it until I started feeling like I was extremely drunk.  Please be very careful with this stuff.  I was in the middle of my universities cafeteria feeling like I was on some heavy drugs.  I only ran into 1 person I knew and I think I handled it alright but I was not in any state to be in public lol, or driving for that matter.  Drove myself right home after.  Titration is very important with this stuff, please use with caution!  I can understand now why Ceretropic doesn't want to sell this stuff in bulk powder, one uninformed guy going full Murica and taking 50 mg first dose could end very badly.  I'm still reeling from it and I've a lot of studying to do and I don't think it's going to get done in the manner I had intended.  Hopefully it subsides by tomorrow for my exam.

 

After the Sz / Memantine connection was brought to my attention I remembered that minocycline, a proven alternative treatment for Sz as well, dealt with NMDA receptors.  I looked it up and low and behold it provides neuroprotection from NMDA neurotoxicity.  Why I never discovered this when I first was looking at Sz I have no clue but it would have been nice to find memantine 2 years ago.  I've never even seen it mentioned on the Sz forums and I militantly ravaged through that database for months, I think it's a basic unknown in the online Sz community.

 

But to the point (sorry hopefully this is cohesive I'm really out of it right now) I felt the effects very quickly, the first day in fact.  Like mentioned before I experience it in 2 states, let's call them "A" and "B".  State "A" comes from my first dose and at first at ~2.5mg it lasted 1.5 - 2.0 hours, and then what happens is I transition almost instantaneously, maybe over like 30 seconds, into state "B" which is much less desirable.  State "B" feels like I'm drunk, I'm uncoordinated, I'm tipsy feeling.  State "A" is the state I'm looking for.  So after titrating up to 20 mg, state "A" lasts about 6 hours before falling into state "B".  I plan on a slow titration to a therapeutic ceiling, wherever that may be, in hopes of increased therapeutic effect and a longer "A" state.

 

 Today while I went way too far way too fast I did experience some enhanced clarity along with the drunk feeling.  I'd read an anecdotal where one guy claims that for him at his high doses (50mg) it took 6 weeks for those side effects to fade and he was left with only the positives, so I'm going to attempt to hold out for a little while before passing judgment on how this is all going to work.  He didn't mention anything (and I'm still trying to find his post again) about the 2 different states thing, but he did say that it took quite some time for the side effects to eventually fade.  So that's basically where I'm at right now in terms of progress. 

 

For the past 7 years, me trying to experience an emotion has basically felt like when you're trying really hard to thread a needle and you just can't get it no matter how hard you try.  That for about 7 years.  Just a full disconnect.  It's gotten a little better now, it's still clunky for me to transition from emotion to emotion but it's definitely better then it has been.  I don't know, but I'm rambling.

 

Let me know how your experience goes and I'll continue to update with my progress.  Cheers!


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#34 Kingsley

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Posted 10 June 2015 - 12:59 PM

 

 

For the past 7 years, me trying to experience an emotion has basically felt like when you're trying really hard to thread a needle and you just can't get it no matter how hard you try.  That for about 7 years.  Just a full disconnect.  It's gotten a little better now, it's still clunky for me to transition from emotion to emotion but it's definitely better then it has been.  I don't know, but I'm rambling.

 

Let me know how your experience goes and I'll continue to update with my progress.  Cheers!

 

 

Thanks for the update, and I look forward to seeing how it turns out for you.  I know how it feels to bang your head against the wall trying to be normal and to do something most people take for granted, and to not understand why you can't.  I imagine science will have the answers to our various issues in 20-50 years but that doesn't help us in the mean time.  

Until then I guess we're in uncharted territory.

 

I am putting off my memantine experiment for the moment.  I have been having some surprisingly good experiences after tweaking my stack a bit and adding NAC.  Plus, I added magnesium back in after realizing that I am likely depleted due to the diuretic effects of vyvanse and all the coffee I drink, and that's been night and day.  We'll see where this goes or if it's another dead end.

 

Good luck and keep fighting the good fight! 

  
 



#35 AlmostEasy

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Posted 11 June 2015 - 07:41 PM

 

 

 

For the past 7 years, me trying to experience an emotion has basically felt like when you're trying really hard to thread a needle and you just can't get it no matter how hard you try.  That for about 7 years.  Just a full disconnect.  It's gotten a little better now, it's still clunky for me to transition from emotion to emotion but it's definitely better then it has been.  I don't know, but I'm rambling.

 

Let me know how your experience goes and I'll continue to update with my progress.  Cheers!

 

 

Thanks for the update, and I look forward to seeing how it turns out for you.  I know how it feels to bang your head against the wall trying to be normal and to do something most people take for granted, and to not understand why you can't.  I imagine science will have the answers to our various issues in 20-50 years but that doesn't help us in the mean time.  

Until then I guess we're in uncharted territory.

 

I am putting off my memantine experiment for the moment.  I have been having some surprisingly good experiences after tweaking my stack a bit and adding NAC.  Plus, I added magnesium back in after realizing that I am likely depleted due to the diuretic effects of vyvanse and all the coffee I drink, and that's been night and day.  We'll see where this goes or if it's another dead end.

 

Good luck and keep fighting the good fight! 

  
 

 

Good to hear!  Do you have a log of your situation and experiences?  I'm curious to see what your symptoms might be / what's worked.  That's a good point on the magnesium, which form are you using?  I'm using glycinate and I don't get much from it even when taking a lot of ritalin / using a lot of coffee.

 

Definitely keep the memantine in mind though, there's been a lot of times I've been onto something exciting only to have it be blown away by some other substance which made me realize I wasn't even close lol.  You can see it happen like 5 times in my main thread, makes me feel like that kid who just can't quite get his life together and is always onto the next get rich quick scheme, though of course it's a little different for us, we're only doing what we can.

 

Best of luck to you as well, hope that stack works out.  I tried NAC back in the day without much luck, have you tried sarcosine at all?  Again it would be good to see your symptoms but NAC / Sarcosine are the top dogs when it comes to negative / cognitive Sz, if NAC helps it might be a good idea to investigate.


Edited by AlmostEasy, 11 June 2015 - 07:42 PM.


#36 Kingsley

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Posted 12 June 2015 - 01:43 PM

 

Good to hear!  Do you have a log of your situation and experiences?  I'm curious to see what your symptoms might be / what's worked.  That's a good point on the magnesium, which form are you using?  I'm using glycinate and I don't get much from it even when taking a lot of ritalin / using a lot of coffee.

 

Definitely keep the memantine in mind though, there's been a lot of times I've been onto something exciting only to have it be blown away by some other substance which made me realize I wasn't even close lol.  You can see it happen like 5 times in my main thread, makes me feel like that kid who just can't quite get his life together and is always onto the next get rich quick scheme, though of course it's a little different for us, we're only doing what we can.

 

Best of luck to you as well, hope that stack works out.  I tried NAC back in the day without much luck, have you tried sarcosine at all?  Again it would be good to see your symptoms but NAC / Sarcosine are the top dogs when it comes to negative / cognitive Sz, if NAC helps it might be a good idea to investigate.

 

 

Nope, no log, though I have benefitted greatly from others logging their experiences.  The magnesium I take is a combination of oxide and citrate, and it also has calcium, so it's possible that is helping me too.  I assumed it was mainly the magnesium helping because it seemed to alleviate another issue I was having with a fast/strong heartbeat, which I understand can be a sign of magnesium deficiency.  Anyway, it's the type of thing that probably only helps if you're deficient.

 

I can so relate to your comment about thinking you have found the answer, wanting to trumpet it to the world, only to find that it is a dead end.  Story of my life.  For example, when I first experimented with l-glutamic acid, I felt essentially cured for the first 2-3 days, only to have the effects diminish.  Same thing with many other supplements, many of which retain a benefit but become much less dramatic over time. 

 

As for my symptoms, I am diagnosed ADHD-PI and have had lifelong problems with focus and concentration.  It runs strongly in my family so I am positive that it's genetic, though I'm the only one who is diagnosed.  I don't feel that the ADHD-PI diagnosis fully captures my symptoms, and I relate more to the emerging concept of Sluggish Cognitive Tempo, which is becoming recognized as its own distinct disorder.  The problem as I see it with the ADHD diagnosis is that it broadly emphasizes problems with attention and focus without really distinguishing between distractibility vs. cognitive sluggishness, both of which can manifest as lack of attention.  My problems are not the distractibility or "mental chatter" typically associated with the ADHD spectrum, but rather cognitive issues like mental sluggishness, horrible working memory, etc.

 

As I said before, my symptoms seem very much in line with the negative schizo symptoms.  Maybe some day when the concept of Sluggish Cognitive Tempo disorder evolves and is fully established (and hopefully gets a better name), it will be recognized as being more related to schizophrenia and glutamate system dysfunction than to ADHD.  My theory is strengthened by the fact that my grandfather, who had similar attentional issues as me his whole life, had a brother who was apparently schizophrenic.  I also have a cousin who seems to qualify.  Something must be going on here.

 

Predictably, the supplements and meds that are the most helpful to me cognitively are glutamatergic in nature.  For example, nothing has been more effective than modafinil, which is theorized to affect this system.  Vyvanse is also very helpful, though it is more about mood, motivation, and wakefulness than cognition for me.  I also benefit from glutamine, glutamic acid, and NAC, and have been experimenting with other supplements that affect the nmda receptor.  My current stack is as follows, in varying dosages.  Aside from basic vitamins, I try to take things that have shown a significant benefit for me on their own.

 

*Vyvanse: mood, drive, wakefulness, and to a lesser extent cognition

 

*Modafinil: currently out of it, but it is a great alternative to vyvanse and actually has a better cognitive effect for me

 

*L-Glutamic Acid: helpful with cognition and alertness.  Not always consistent

 

*L-Glutamine: similar to glutamic acid.  Hard to say which is more effective

 

*NAC: Sort of like windex to my cognition.  Doesn't greatly affect mental energy but adds clarity.  Still experimenting with it but it is likely a permanent addition

 

*Grape seed extract: Surprisingly helpful with cognition and alertness and another example of something that was amazing at first but became attenuated over time.  Mechanism unclear: possible COMT inhibitor?

 

*Phosphatidylserine: Was very surprised to see a significant acute effect on cognition.  Depends greatly on the brand and again, not always consistent

 

*CDP-choline: mental energy

 

*SAM-E: can be very helpful for cognition, though I have found that too many methyl donors can put me into a stupor.  Still figuring out the right balance

 

*Methyl folate: I am homozygous for the C667T MTHFR mutation, so I have problems metabolizing folate.  However, I am still figuring out the right balance for methyl folate.  Sometimes it is greatly effective and others it puts me into a stupor.  Work in progress.  Same thing with Methyl B12.
 

I have tried many other supplements but the above are the current keepers.  I am currently experimenting with sarcosine and I can't say that I have noticed a huge benefit, though it may be helping.  May need to up my dosage.

 

The memantine is sitting in my medicine cabinet awaiting its turn.  It will get its chance sooner or later.  I will be sure to post my results.


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#37 Kingsley

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Posted 14 July 2015 - 05:19 PM

AlmostEasy:

 

How goes the memantine treatment?



#38 AlmostEasy

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Posted 17 July 2015 - 10:01 PM

AlmostEasy:

 

How goes the memantine treatment?

 

Howdy!

 

Well it's still effective but I elected to put it down for a little bit after some of the dissociation caused some uncomfortable situations at school.  That weird shift from phase A to phase B was just to bizarre.  In the middle of a conversation I could go from normal to confused almost instantly.  I knew it was hitting the right switches but maybe not for the wrong reasons, but not from a pathway that is treating the cause and I think I'm onto what's really going on.

 

EDIT:  just realized you have MTHFR issues too!  Imagine that xD

 

I looked at MTHFR mutations a long time ago and tried one of the protocols with no success.  It was suggesting folate levels of 400 mcg and hydroxycobolamin, which is key to the methylation block.  methylfolate and b12.  I've now found out that some people actually require HUGE doses of folate and METHYLcobolamin and once I started going down that path I've been getting pretty awesome results.  It's been a gigantic process to figure everything out for what I need personally but I think this is the actual cause and I think I know why memantine helped so much

 

"Homocysteine is toxic to neurons via direct DNA damage and excitotoxicity, inducing apoptosis" - http://www.sciencedi...213158212000174

 

Homocysteine is highly elevated in individuals with MTHFR ( and COMT/ VDR Taq / MTRR etc etc) mutations and it's very likely this is why it was helping me so significantly.  The pieces are starting to fit together and the results I'm getting from my methylation protocol are too significant to ignore.  I was still on edge scared of getting too excited even when it was working but after some time I can't deny how much sense it makes and how good the results are.

 

Once I get everything streamlined in this protocol and I research more and fill in all the cracks I'll definitely give memantine a try again to see if it's still needed.  I may even do it sooner, it's very tempting.  The only downside was that dissociation and that bizarre crash I would get after 5 hours that made me go from like a 9 to a 3 almost instantaneously but maybe after supplying my body with some crucial things it was lacking that won't happen anymore.  If that's the case I will continue to use it.


Edited by AlmostEasy, 17 July 2015 - 10:02 PM.


#39 Kingsley

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Posted 20 July 2015 - 03:40 PM

Interesting.  I'm pretty familiar with methylation protocol as I've explored it myself to good effect.  I'm skeptical that elevated homocysteine itself could cause the dramatic symptoms that you have described, especially in a young man, but who knows?  Or maybe it is a contributory factor along with some other issues.  And, of course, methylation has a lot of other important purposes including the production of SAM-E, which drives countless processes in the body.

 

One bit of advice.  After having initial success on a methylation protocol, I found after a while that methyl donors were making me feel sick and zombified, even in small doses.  The problem resolved when I began supplementing potassium.  There is a lot of anecdotal evidence out there of methylation increasing the need for potassium, so you may want to consider at least eating more bananas and potentially buying a bottle of potassium supplements.  Also, there is some speculation that dramatically increasing certain B vitamins may deplete others.  So, you may want to invest in a good base B multivitamin.  I like Country Life brand co-enzyme b-complex advanced. 

 

I haven't tried memantine yet either, though I have a supply of it and am curious.  I am having exciting results myself having re-added methyl folate and b12 and other base vitamins and minerals, including IRON, which has been dramatically effective for me.  I believe that high dose grape seed extract and green tea for years may have depleted me, as polyphenols can dramatically decrease iron absorption.  Add to that sarcosine, NAC, and 5-htp, which have all produced significant results on their own and appear to be key to my neurochemistry (my genetic profile indicates significant mutations affecting nmda receptors and serotonin metabolism), and things are looking better than they have in years for me.

 

Happy to hear of your success, and keep us posted.  Keep potassium in mind!

 

 



#40 Kingsley

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Posted 08 March 2016 - 06:13 PM

AlmostEasy:

 

Any chance of an update on your progress?



#41 medievil

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Posted 08 March 2016 - 08:17 PM

 Wow. I just read your original post and your symptoms are almost exactly what I deal with every single day. PAWS. Low testosterone. All the negative shizo symptoms. but also dealing with IBS and possibly Candida. 

 

I am not having much relief. And yes the stimulants have temporary benefits but not worth it long term. Some of the more promising days I have had this year were from low doses of pregnenolone. Around 5mg but it's inconsistent unless you get the cream. Last year royal jelly had some benefits but these days it gives me terrible die off reactions so I have to avoid it. Royal Jelly can rejuvinate pituitary + dozens of other health benefits. 

 

I tried Mementine about 2-3 years ago when I had a small trial. It gave me the most astonishing cognitive boost I may have ever felt!! I was beginning to feel like a genius again. Everything was flowing so freely after 1 and a half days. I could effortlessly type some brilliant paragraphs full of profound insight and advanced vocabulary. Absolutely unlike what I am capable of right now.  Unfortunately at about the 2 day mark I started to feel really creepy and strange. It was even a bit fearful. Maybe a bad reaction with other meds as I was taking ritalin and likely some SSRI at the time + who knows what else but this strange fear crept over me intenselyyy and I felt I absolutely had to stop taking it. If I find my journal I may be able to describe what it was exactly but I know I felt very very strange. And I was taking low doses as well. The long half life meant it took a while to build up and thus a while to leave the system.

 

Does anyone know why such a side effect would emerge? It may have been detachment from my surroundings along with some very real dysphoria.   And how might it be prevented?? Any precautions to take with memantine or anything I should not be taking with it?   Because the cognitive boost was an absolute MIRACLE but the side effects were terrifying.

 

I would like to try memantine again but the doctor was unwilling to give it to me and my old ones are long expired unfortunately. 

Hi, most of the members wont know this but im responsible for the current widespread use of memantine for the treatment of many mental illnrss or drug tolerance, before i promoted it for the prevention of tolerance to most meds it was pretty much unheared of on most fora.

 

That said, amphetamine will work as long term treatment for negative symptions in shizophrenia in combination with memantine or dxm for the prevention of tolerance, eventually depending on the individual in combination with a one day break a week.

 

I suffer from predromal shizophrenia myself and am pretty much a expert on the subject, im planning on making a thread about the treatment of shizophrenia, either way if you have any question or others with regards to shizophrenia, please email me at

wesley452266@gmail.com
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#42 AlmostEasy

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Posted 10 March 2016 - 02:09 AM

AlmostEasy:

 

Any chance of an update on your progress?

 

Hiya!

 

I've been doing trial and error on a whole assortment of things, but I'm not using memantine quite as much anymore.  It does work to some extent but it lost that true power it had, though it's still one of my stronger supplements.  I'm definitely feeling like the effective part of it was it's microglial inhibition, which you can read fully about here:

 

http://forums.phoeni...hibitors.34164/

 

I'm also into a pretty advanced methylation protocol.  10mg x 3 methylcobalamin injections daily, 20mg x 3 methylfolate along with all kinds of cofactors and other b vitamins.  Also potassium ;) oh and I don't know if you're on a methylation protocol but copper has been huuuge with this, it's been crucial for me.  It took me a while to believe it but the results were the results, I was scared of copper for some time.

 

That is helping SOME but I can tell something major / fundamental is missing.  BH4 (Tetrahydrobiopterin) may be one of our answers, as it's certainly low in those with the CBS mutation leading to increased ammonia in the body, which steals BH4 away from making neurotransmitters.  I've received some BH4 in the mail but it's most likely degraded as it was out shipping for who fucking knows why for 10 days straight on 1 ice pack.  Another online friend I chat with that has almost identical issues has massive benefit from it, his was only out in the post for 3 days.  I'm going to have to get a refund or new order to really see if it's the real deal or not.  The 1st day was very very intriguing, less so today.  I had it in the fridge, probably should've been in the freezer.  We're working on some other sources for it.

 

Asides from that I've tried Low Dose Naltrexone which was a life saver at first, possibly for it's microglial inhibiting effects as well, but that has faded as well, of course.  The effects that do remain from it are a complete elimination of my erectile dysfunction.  It started getting pretty bad.  I don't know what is causing it.  I take testosterone and my levels are fine.

 

I've also started to trial higher dose Acyclovir for my EBV, but this can take many many months to see the results of.  Dr. Lerner, a ME/CFS doctor, uses 1.5g x 4 daily with 70+kg patients.  I'm doing 800mg x 5 daily.

 

Memantine though is still a big one for me.

 

Asides from the hope with BH4 I'm not too sure where I'm going to go with it.  Some in the ME/CFS community (I highly recommend checking out that website, the main page, and going through all the pages and drop down menu's and just thoroughly getting a feel for it) are doing well with the Brewer Protocol using Amphotericin B and/or Nystatin, as mycotoxin's / fungus in the brain can apparently be an issue.

 

For advanced methylation definitely check out "My Current Understanding of Freddd's Protocol".  Freddd really led the way on it, he's a member of the Phoenix Rising board, good stuff.

 

Overall I'd say I'm fairly discouraged.  It's asinine to have put SO much effort into every possible scenario and see most people doing significantly better with 1/4 the effort put in.  If BH4 truly isn't the answer I don't know what I'm going to do.  I'm sure new avenues will pop up but wow it's been a long haul.

 

I wish I had more answers, it's basically all I work on and think about 24/7 when I'm not dealing with university full time.  There's a lot of us trying very hard but the answers seem to be eluding us.

 

Making any progress yourself?


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#43 BobbyDick

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Posted 11 March 2016 - 08:16 AM

Memantine repairs cholinergic system.
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#44 Kingsley

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Posted 11 March 2016 - 06:36 PM

It's really interesting how closely your experiences track mine. Like you I have tried a lot of different avenues, many of which gave me huge gains that faded with time. Tolerance really is the dream killer.

Like you I was all about methylation for a while and was convinced it was the answer especially in light of my homozygous MTHFR status. However, the magic wore off, though I do find it important to keep up with my folate. Also like you, I had huge gains with copper and figured I must be deficient. I believe the gains I got from copper have held somewhat though it was not the magic bullet. I am familiar with Freddd's protocol and all the methylation jabber over at the Rising Phoenix Forum, though my current opinion is that it's a lot of pseudo-science. But that's a discussion for another day.

Also like you, I became fascinated with BH4 as the potential holy grail, though I have not been able to obtain any and past experiences suggest I should not get my hopes up. I intend to try it when I can, and will be interested to see if you ultimately make gains on it.

I came to a similar conclusion as you regarding micro-glial activation and brain inflammation and experimented with many anti-inflammatory supplements with mostly dead ends. HOWEVER, one supplement, n-acetylglucosamine, has been giving me gains that have all but convinced me that my problem is neuroinflammation. The best I can describe it is that with NAG my brain begins to actually process information, though it is not the least bit stimulating.  As a result, it dramatically improves my work performance, my interaction with people, and thus my mood. 

I totally relate to the letdown and frustration that comes with failure after failure, and am also in touch with some other people on this forum searching for answers.  Like you (again) a good portion of my day goes into trying to find a solution.  I think I may be onto something big with the idea of neuro-inflammation and NAG in particular, though time will tell.  Please try it if you have not already--couldn't hurt, though of course we both know to manage expectations. 


Edited by Kingsley, 11 March 2016 - 07:02 PM.


#45 AlmostEasy

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Posted 12 March 2016 - 02:03 AM

It's really interesting how closely your experiences track mine. Like you I have tried a lot of different avenues, many of which gave me huge gains that faded with time. Tolerance really is the dream killer.

Like you I was all about methylation for a while and was convinced it was the answer especially in light of my homozygous MTHFR status. However, the magic wore off, though I do find it important to keep up with my folate. Also like you, I had huge gains with copper and figured I must be deficient. I believe the gains I got from copper have held somewhat though it was not the magic bullet. I am familiar with Freddd's protocol and all the methylation jabber over at the Rising Phoenix Forum, though my current opinion is that it's a lot of pseudo-science. But that's a discussion for another day.

Also like you, I became fascinated with BH4 as the potential holy grail, though I have not been able to obtain any and past experiences suggest I should not get my hopes up. I intend to try it when I can, and will be interested to see if you ultimately make gains on it.

I came to a similar conclusion as you regarding micro-glial activation and brain inflammation and experimented with many anti-inflammatory supplements with mostly dead ends. HOWEVER, one supplement, n-acetylglucosamine, has been giving me gains that have all but convinced me that my problem is neuroinflammation. The best I can describe it is that with NAG my brain begins to actually process information, though it is not the least bit stimulating.  As a result, it dramatically improves my work performance, my interaction with people, and thus my mood. 

I totally relate to the letdown and frustration that comes with failure after failure, and am also in touch with some other people on this forum searching for answers.  Like you (again) a good portion of my day goes into trying to find a solution.  I think I may be onto something big with the idea of neuro-inflammation and NAG in particular, though time will tell.  Please try it if you have not already--couldn't hurt, though of course we both know to manage expectations. 

Hahaha, oh man.  I did use NAG for a bit there, forgot to mention since unfortunately it did fade.  I went up to 2.1 grams x 2 daily.  I don't notice the effects much anymore.  I found Low Dose Naltrexone to be quite an amazing augment to it but it's a tricky one (faded mostly).  Sometimes it will stick if I skip a day, I might play with every other day.  Ugh.  

 

Phenibut I should also mention is amazing for restoring cognition.  I'm thinking of doing 2 week cycles, it's really nice mentally just to have some relief for a bit and have actual enjoyment.  I feel like my GABA system is drastically under performing.  Inositol was big for a bit too but I get SO much fatigue from it that I can't handle it.

 

Have you tried Minocycline or any other antibiotics?

 

This was interesting as well:

http://forums.phoeni...-fatigue.41749/

 

Also going to try Liposomal Vit C.  Oral absorption I've seen claimed as low as 3%.  On paper Vit C looks like the holy grail for NO/ONOO scavenging and BH4 / Folate recycling.  I've ordered the infamous LivOn professionally made product and if that works I'll switch to home made.  It's supposed to be more effective than even IV Vit C.

 

We should definitely chat though, do you have Skype?  There's about 10 of us chatting on the platform Slack trying to figure things out.  If you want to PM me an e-mail I can invite you can we can chat there.  We should definitely swap ideas.  There's 2 others on there that do some pretty hardcore researching as well.

Also we have some sources for BH4 if you're interested.


Edited by AlmostEasy, 12 March 2016 - 02:14 AM.


#46 AlmostEasy

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Posted 12 March 2016 - 02:15 AM

Memantine repairs cholinergic system.

 

In what context?  Acutely while it is active or chronically from continued use?  I do not receive benefit when it is not in my system in any way.



#47 Kingsley

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Posted 14 March 2016 - 04:02 PM

Not surprising you've been there done that with the NAG.  I'll PM you my email for the Skype discussion.



#48 BobbyDick

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Posted 16 March 2016 - 08:57 PM

To low and to high level of ACH give the similar symptoms. To low level of ACH causes insufficient activation of nicotinic receptor. To high level of ACH causes blockade of depolarisation and in effect blockade of receptor.

Memantine is voltage-dependent antagonist of nicotinic receptor. That means the stronger receptor is activated, the stronger memantine block it.

Memantine and nicotine patch (small part of patch) optimize activation of cholinergic system.

#49 Londonscouser

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Posted 30 March 2016 - 04:04 AM

Just wondering if the mementine is still working for you ?

 

I got pretty similar symptoms to you, in regards to reduced ability to socialize, no emotions, ect from smoking weed everyday....



#50 komputerhead

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Posted 24 November 2016 - 11:13 AM

I'm on week 3, slowly moved up 5ml per day to now at 15ml per day in the evening, I source from alldaychemist, I feel amazing, I feel calm and relaxed unphased by things, I bumped a plate on the table and turned and grabbed it before it fell, I noticefl I did it but did not feel the usual spike of adrenalin or rush I usually get. Work is going well, I have quite a bit of pressure and work in IT doing everything, I'm coping well. This is the most amazing thing I have ever taken, I have dextroamphetamine on prescription and I was taking it very regularly, the amount required has come down, about 20mg roughly a day. I am smiling more, my internal dialogue and grumpy pants has faded and it is no where near as strong as it used to be, I feel more carefree and cool even, it's quite amazing .My reading and focus has improved too. I have been recovering myself from a subarachnoid hemorrhage I had 5 years ago. My mood, focus, reading and working memory had all been impacted or changed as a result, this seems to have put so much right.

#51 jack black

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Posted 24 November 2016 - 03:08 PM


 

I've been doing trial and error on a whole assortment of things, but I'm not using memantine quite as much anymore.  It does work to some extent but it lost that true power it had, though it's still one of my stronger supplements.

 

 

so, it wasn't a cure after all? how long did it take to build tolerance? did you try taking a brake from it? any other updates?


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#52 Xptriate

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Posted 25 November 2016 - 01:08 PM

Memantine repairs cholinergic system.


I am suffering the same issues as OP and i came to the conclusion it is an issue in cholinegic system.

OP i think your answer is in BobbyDick one line post.

Maybe if you got a vagus nerve stimulator you would feel great. Im looking into that

#53 AlmostEasy

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Posted 09 December 2016 - 10:51 PM

After lots more trial and error and learning and research, it's quite obvious that memantine could never be a "cure" as it is covering up something that went wrong.  It was a solid band aid.  It definitely lost its magic but I come back to it now and again when I'm feeling really down and just need something, anything to help.

 

I've put literally hundreds of substances in my body and it's become so clear after this monumental effort that something needs to be removed, not added.  I did the IGeneX Lyme testing and I'm CDC negative for Lyme but positive by IGeneX standards.  Some of the positive bands are Lyme specific.

 

I could just have an extremely neuro dominant Lyme disease.  Fairly soon here I'm going to be attempting to get my GP to coordinate with an LLMD in my general area and see if we can start some heavy antibiotics of some sort.

 

Other things since then that I've found helpful:
 

  • Low Dose Naltrexone (lasted about 4 weeks)
  • Ipamorelin + CJC 1295 w/o DAC (200mg/200mg 3x / day) - $$$.  Super helpful at first, almost curative.  Memantine level.
  • Semax / NA-Semax injection/spray - Was always so nice to feel but even that quit working for me.  Semax tolerance is almost unheard of.
  • High dose T3 up to 150 mcg / day.  Studies show it helps push out Lyme toxins clogging up T3 receptors.  Quit working ofc.
  • Hydrocortisone ~25 mg / day.  I ate the Cortizone 10 ointment (not cream).  Yes you read that right.  It's petroleum jelly and HC.  Worked so well for a while.  Does nothing now, weened off.  Careful with this one.  I got the generic prescription tabs and they were shitty, didn't do anything really.
  • H2 Blockers (Zantac) - Really sharpened my environmental awareness.  Felt like I was in the world again, sociability went through the roof on it.  I tried 3 different types, Zantac being 1 of them.  Stopped working, might've made me start feeling bad too actually.  Messes with stomach acid.
  • Sarcosine 2-4g/ day.  Still playing with this one but it's been helpful.  I think it's starting to crap out though, we'll see.

Why these stop working I'm not sure I'll ever know, it's like my body literally adapts to what I put it in, like the inflammation corrects itself for every correction made to it.  I have read nothing to explain why that might be happening.

 

I'm sure if it's Lyme it has infested my HPA and is wreaking havoc there.  It's amazing that the T3 / GH peptides / HC do not continually work.  I'll never understand that.  I've heard if you have poor signaling taking legit Growth Hormone can be the way to go but I haven't went that route yet.  I'm also interested in IGF peptides, but haven't got there yet.  

 

I'm mostly concerned with trialing some legitimate antibiotic regimens.  If those fail to do anything, and I give it a good honest go, I think it's probably onto Valcyte and ME/CFS specialists.  Testing for more HHV-6 and coxackievirus or something.  Maybe a flagyl trial for gut stuff, or Xifaxan for SIBO.  I ran a heavy trial of Flagyl that I got from oversea's as someone cured their fog with it, they had some gut bug wreaking havoc in them.  I did a heavy 7 day trial with almost zero effects of any kind.  The only way I could tell I was taking anything was a metallic taste in my mouth.  Weird stuff.

 

I somehow passed my medical program, got my bachelors degree, so that's good.  Soon here I'll have some actual cash to start throwing at this problem instead of spending thousands of hours behind my computer trialing supplements and oversea's pharmaceuticals.  Not to knock that, it's an invaluable part of the process but this is going to take some major assistance to tackle.


Edited by AlmostEasy, 09 December 2016 - 10:57 PM.

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#54 jack black

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Posted 10 December 2016 - 02:49 AM

thanks for the update! i've got different issues of course, but have been experimenting with supplements for 2 years now, and it has been sort of fun and i gained a lot of insights how body/brain works. it's a valuable experience.


Edited by jack black, 10 December 2016 - 02:50 AM.

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#55 Omega 3 Snake Oil

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Posted 14 December 2016 - 07:19 PM

I'm on bee venom therapy for Lyme, I didn't realize it worked on dementia as well

 

Another treatment to consider looking into IMHO is BEE VENOM THERAPY.

http://www.medicalda...dementia-230959

 


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#56 BioFreak

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Posted 15 December 2016 - 10:52 AM

Just wondering... Did you ever consider nutritional sensitivities? Those may not show up in blood tests, like casein (casomorphins), soy, lectins,....

 

I've had quite some of your problems and they got massively better after I went on a low protein diet. I later figured out that lectins in lentils, soy, and probably the casein in milk products (casomorphins!) were the cause for a lot of my problems (not high protein itself).

I'd go on an elimination diet for 2 weeks and if you have a massive improvement in symptoms, you've actually found a basket of root causes (one or more of the ingredients of your normal meals). In fact thats the only way to reliably confirm many food sensitivities, and then there is the fact that you can rule out a LOT of factors within just 2 weeks. Actually, symptoms should decrease even faster then after 14 days, depending on the insensitivity I guess. But after 14 days, the body is more sensitive when you reintroduce foods and if you have a food sensitivity, you should certainly feel the difference when reintroducing it.

 

If you want some tips for the elimination diet, just ask.

 

I personally did not consider this for years, especially not blaming milk products since I was heavily consuming them(and heavily relying on a high protein diet for weight training)... But it was one of the best decisions I ever made. Now I can finally again sleep through the night, and have lots of symptoms reduced or completely eliminated.


Edited by BioFreak, 15 December 2016 - 10:53 AM.

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#57 .Moose.

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Posted 18 December 2016 - 11:26 PM

Just wondering... Did you ever consider nutritional sensitivities? Those may not show up in blood tests, like casein (casomorphins), soy, lectins,....

 

I've had quite some of your problems and they got massively better after I went on a low protein diet. I later figured out that lectins in lentils, soy, and probably the casein in milk products (casomorphins!) were the cause for a lot of my problems (not high protein itself).

 

That's really interesting, personally I was wondering if I had something similar to PKU, which is treated with a similar diet to that which you mentioned...



#58 BioFreak

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Posted 19 December 2016 - 07:37 PM

I just found out that memantine does actually activate histamine neurons in the brain. Maybe there is some connection to the cause of your problems, along the lines of histamine intolerance or mast cell activation syndrome. Still, it would be quite a paradox, if memantine activates histamine neurons, as well as histamine itself, yet memantine improves symptoms, while histamine should worsen it (if thats your problem)



#59 jack black

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Posted 20 December 2016 - 04:33 AM

I just found out that memantine does actually activate histamine neurons in the brain.


This is news to me. Are you sure?
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#60 Dichotohmy

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Posted 20 December 2016 - 07:20 AM

I just found out that memantine does actually activate histamine neurons in the brain. Maybe there is some connection to the cause of your problems, along the lines of histamine intolerance or mast cell activation syndrome. Still, it would be quite a paradox, if memantine activates histamine neurons, as well as histamine itself, yet memantine improves symptoms, while histamine should worsen it (if thats your problem)


Memantine seems to be an H3 agonist, and with H3 being an autoreceptor, would presumably worsen a mast cell disorder rather immediately due to the H3 agonism leading to more histamine synthesis and release from other histamine receptors. I agree a mast cell disorder or other histamine intolerance is too paradoxical given the OP's experience.

Http://forum.mindandmuscle.net/38826-memantine-activation-brain-histaminergic-neurotransmission

Memantine also showed some significant promise for me in the short term. Unfortunately, this promise was entirely in the titration and in fact, holding at a low dose like 5-7.5mg once a day, memantine's benefits vanish after about 4 weeks. I mention that dosage because once I got to around 10-12.5mg once daily, the dissociation was just too much and didn't seem to get better.

I suspect the titration love was due to memantine also being a weak-mild dopamine-agonist and limbic dopamine activation enhancing endorphin release and endorphins release thus calming the malaise promoting cytokine release by the immune system. The dopamine system seems to do WTF it wants, though, and inevitable tolerance to dopaminergic interventions is reality.

Edited by Dichotohmy, 20 December 2016 - 07:24 AM.






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