# Possible tolerance prevention for dexedrine/adderall?



## Canadian4Life (Sep 27, 2010)

I am on dexedrine and take 10mg since I started and still am on 10mg a day (spansule). I take 600mg of lithium a day too and I have read some studies showing how nmda receptor antagonists can stop or prevent tolerance to stimulants like dexedrine or adderall. There have been studies showing that lithium has nmda receptor blocking effects too.

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http://jop.sagepub.com/content/24/4/585.abstract
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anyone know if lithium can be helping my tolerance to the dexedrine I am on. I took it a few years back when I wasn't on lithium and I was on 30mg a day and still no better benefit.


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## Xande (Jul 18, 2011)

Memantine is supposed to help with tolerance to adderall. Of course you have to get it prescribed first and also have to see if you can put up with any side effects you might get.

DXM is also said to help with tolerance to adderall, I personally don't feel too comfortable taking DXM on a daily basis while taking an SSRI due to the possibility of serotonin syndrome.

Chelated Magnesium is also supposed to help. I started taking this and actually find it helpful for sleep. Not sure if it has helped with tolerance at all, but great sleep aid.


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## Canadian4Life (Sep 27, 2010)

Xande said:


> Memantine is supposed to help with tolerance to adderall. Of course you have to get it prescribed first and also have to see if you can put up with any side effects you might get.
> 
> DXM is also said to help with tolerance to adderall, I personally don't feel too comfortable taking DXM on a daily basis while taking an SSRI due to the possibility of serotonin syndrome.
> 
> Chelated Magnesium is also supposed to help. I started taking this and actually find it helpful for sleep. Not sure if it has helped with tolerance at all, but great sleep aid.


Yeah I don't want to ask my doctor for memantine to help tolerance not adding another drug. DXM forget that .. wouldn't use that either. Magnesium glycinate 500-750mg at night I take helps a bit. BTW I'm on a low dose of zoloft so DXM would be a no for that reason as well


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## Under17 (May 4, 2010)

Definitely go with acamprosate, memantine, or both. Dosage and timing, all that stuff is basically up to you to discover, there's so many different ways to approach this I wouldn't even know where to begin. But I think 40 mg memantine a day and 1332 mg of acamprosate is the most recommended, or something like that. I haven't got my acamprosate yet so I don't know all about it. You can get either one without a prescription from certain Indian online pharmacies, some of them open all day, and have reliable chemists. It's semi-legal in US and probably no one cares much about it in Canada but I could be wrong.

Oh and curcumin too I would take.


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## Xande (Jul 18, 2011)

Canadian4Life said:


> Yeah I don't want to ask my doctor for memantine to help tolerance not adding another drug. DXM forget that .. wouldn't use that either. Magnesium glycinate 500-750mg at night I take helps a bit. BTW I'm on a low dose of zoloft so DXM would be a no for that reason as well


Wow that's a lot of magnesium lol. I only take 300mg of supplemental magnesium at night time, especially since I looked up the max amount of supplemental magnesium a person should take a day is 350mg (office of dietary supplement site, I think it was).

Does magnesium help you sleep as well?


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## Echonnector (Sep 12, 2010)

*Answers*



> Memantine is supposed to help with tolerance to adderall. Of course you have to get it prescribed first and also have to see if you can put up with any side effects you might get.
> 
> DXM is also said to help with tolerance to adderall, I personally don't feel too comfortable taking DXM on a daily basis while taking an SSRI due to the possibility of serotonin syndrome.
> 
> Chelated Magnesium is also supposed to help. I started taking this and actually find it helpful for sleep. Not sure if it has helped with tolerance at all, but great sleep aid.





> You can get either one without a prescription from certain Indian online pharmacies, some of them open all day, and have reliable chemists. It's semi-legal in US and probably no one cares much about it in Canada but I could be wrong.


Both of these suggestions pretty much give you the best methods to prevent further tolerance/possibly reverse it and a means by which you can obtain the necessary materials. I'm sure it shouldn't be too hard to find an online source for anything you cannot get OTC, and being in Canada only makes it more likely you may find a domestic source online.
Personally I know a pretty decent site that actually offers a decent range of both z-benzos and benzodiazepines, ritalin, tramadol etc. Not all of them are indian. Aside from getting pharms to assist your cause, there are _alternative_ chemicals you could consider as well. Be careful about which you use, don't wanna get scammed or worse.

Aside from using tolerance prevention strategies you could always find a substitute for dexedrine that you can use basically so that you are able to take vacations/periods of abstinence from using dexamphetamine, helping add to your tolerance. The key here would be to incorporate the memantine and other tolerance reduction methods into use while using a substitute stimulant that will not exhibit a very strong cross tolerance/perhaps has a different mechanism of action since amp isi primarily a DA releaser that prevents reuptake via some monoamine effect. A typical dopamine/norepinepherine reuptake inhibitor perhaps at more mild doses since you wanna assure you dont incite cross tolerance.
I couldn't really say what you should use if you chose this, I am certainly no licensed doctor and I wouldn't tell you should do anything that may be in conflict with your ethics or the law. I know ephedra is often something I've heard of college students using to study with. Not sure if ephedra is legal. I looked up this link for you, discussing modafinal and dex for purposes like yours and even asks about nmda antagonism for both. You may be able to get modafinal/nuvigil from your doc, if not the online pharmacies may carry adrafinal, the prodrug of modafinal that you dont need a script for

There are a few classes of chemicals that would work for this purpose, some belonging to phenethylamine classes like amphetamine, also there are cathinone family drugs that may suite you're needs for example Wellbutrin, piperidines like ritalin, "wakefullness enhancers" like modafinal or its legal prodrug adrafinal, pyrovalerones...the list goes on, but the classes are ones you can do some research on to see if there are any chemicals that meet your criteria.


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## Echonnector (Sep 12, 2010)

Here is an excerpt that I feel successfully explains and informs people about the general concept of nmda antagonism and amphetamine/drug tolerance and gives them multiple options with thorough explanations of each


> Almost everyone's opinion on using speed/amphetamine/meth is that the best highs were the first two (or three). That is also the case with me.
> When I first tried speed I've used very small amount (I'd say it was around 50 mg) of rather pure amphetamine and damn, it was the best day of my life :] I remember that I was euphoric for around 12 hours, I couldn't stop talking, the music sounded extremely well, I was full of motivation and never felt better in my whole life. Afterwards I had no comedown.
> My second attempt wasn't as fantastic, but also wonderful. Since then I've never achieved that extremely euphoric sensation with my head tingling from pleasure and my insides screaming "DAMN I FEEL ****ING AWESOME!!!". After a year of my speed usage and trying doses even four times as high as the 1st amount I tried - I never came close to that feeling. Sure, I can be motivated, energetic, have a great time during the tweak, be very sociable, but it is still not like during the first two times. I'm aware that amphetamine tolerance develops very quickly and stays at that level for a long period of time (even when taking breaks), so lately I've been doing some online reading on that subject.
> 
> ...


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## Canadian4Life (Sep 27, 2010)

Echonnector said:


> Both of these suggestions pretty much give you the best methods to prevent further tolerance/possibly reverse it and a means by which you can obtain the necessary materials. I'm sure it shouldn't be too hard to find an online source for anything you cannot get OTC, and being in Canada only makes it more likely you may find a domestic source online.
> Personally I know a pretty decent site that actually offers a decent range of both z-benzos and benzodiazepines, ritalin, tramadol etc. Not all of them are indian. Aside from getting pharms to assist your cause, there are _alternative_ chemicals you could consider as well. Be careful about which you use, don't wanna get scammed or worse.
> 
> Aside from using tolerance prevention strategies you could always find a substitute for dexedrine that you can use basically so that you are able to take vacations/periods of abstinence from using dexamphetamine, helping add to your tolerance. The key here would be to incorporate the memantine and other tolerance reduction methods into use while using a substitute stimulant that will not exhibit a very strong cross tolerance/perhaps has a different mechanism of action since amp isi primarily a DA releaser that prevents reuptake via some monoamine effect. A typical dopamine/norepinepherine reuptake inhibitor perhaps at more mild doses since you wanna assure you dont incite cross tolerance.
> ...


Thanks, I think breaks will be the best help for me. I'm not looking to add anything else right now. Yes ephedra is available where I live. Ephedrine comes in 8mg tablets in bottles of 50 (cheap too under 10 bucks) and there is no set number of bottles you can buy. Tried it before and actually found it to be good stuff! definetly going to give that stuff a try again on breaks!


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## Canadian4Life (Sep 27, 2010)

Xande said:


> Wow that's a lot of magnesium lol. I only take 300mg of supplemental magnesium at night time, especially since I looked up the max amount of supplemental magnesium a person should take a day is 350mg (office of dietary supplement site, I think it was).
> 
> Does magnesium help you sleep as well?


Yes magnesium definetly helps me sleep it's great stuff


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## Opiman (Aug 8, 2011)

Echonnector said:


> There are a few classes of chemicals that would work for this purpose, some belonging to phenethylamine classes like amphetamine, also there are cathinone family drugs that may suite you're needs for example Wellbutrin, piperidines like ritalin, "wakefullness enhancers" like modafinal or its legal prodrug adrafinal, pyrovalerones...the list goes on, but the classes are ones you can do some research on to see if there are any chemicals that meet your criteria.


That's a pretty broad suggestion for drug substitutions. I tried doing some research but there are literally a hundred+ drugs that fall under these classes. Any more specific suggestions?


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## Echonnector (Sep 12, 2010)

Opiman said:


> That's a pretty broad suggestion for drug substitutions. I tried doing some research but there are literally a hundred+ drugs that fall under these classes. Any more specific suggestions?


Of course, the problem that comes up then is availability/legality of the substitutions you seek. If you want a more comprehensive list I'd suggest having a private chat with someone that may be able to discuss sensitive information in a more secure form of communication


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## crayzyMed (Nov 2, 2006)

If memantine is too hard to get, lithium may (with a big questionmark) work due to its upregulation of D2 receptors in the striatum.


> Effects of lithium on dopamine D2 receptor expression in the rat brain striatum.
> Kameda K, Miura J, Suzuki K, Kusumi I, Tanaka T, Koyama T.
> Source
> Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, Japan. [email protected]
> ...


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## crayzyMed (Nov 2, 2006)

Echonnector said:


> Here is an excerpt that I feel successfully explains and informs people about the general concept of nmda antagonism and amphetamine/drug tolerance and gives them multiple options with thorough explanations of each


That stuff was posted on bluelight years ago i dont really agree with their explanation tough.


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## The Professor (Jul 31, 2011)

Canadian4Life said:


> I am on dexedrine and take 10mg since I started and still am on 10mg a day (spansule). I take 600mg of lithium a day too and I have read some studies showing how nmda receptor antagonists can stop or prevent tolerance to stimulants like dexedrine or adderall. There have been studies showing that lithium has nmda receptor blocking effects too.
> 
> ```
> http://jop.sagepub.com/content/24/4/585.abstract
> ...


Magnesium is good for tolerance. It keeps it it yor system longer longer too. Supposedly cheleated magnesium is bad though. The best is Magnesium Glycinate, I just got some it is good.

This link talks about a lot of ways to prevent neurotoxicity from ampohetamines. Skip through the first posts if you want. I'm thinking turmeric (curcumin), CoQ10, and magnesium will be good for me.

The one thing I'm unclear about is that magnesium is considered a NMDA receptor antagonist! All of the other substances in this category are harmful to the brain so I don't see how magnesium isn't too. I'm probably way off on this, but from what I understand only 1/20 of the magnesium gets into your brain so that is what makes it safer than the others... I'm really not sure though, does anyone know?


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## crayzyMed (Nov 2, 2006)

I was allways under the impression magnesium is too weak, any long term succes reports?


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## Xande (Jul 18, 2011)

The Professor said:


> Magnesium is good for tolerance. It keeps it it yor system longer longer too. Supposedly cheleated magnesium is bad though. The best is Magnesium Glycinate, I just got some it is good.


How is chelated magnesium bad? I take chelated magensium in the form of magnesium glycinate. I thought chelated was just supposed to mean more bio-availability.

Been taking magnesium past three weeks, don't know how well it works for tolerance, as I've only been on adderall for a month.

Haven't noticed a decrease in tolerance, so that's good. But I'm also a small dosage of 15mg daily.


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## The Professor (Jul 31, 2011)

hmm... chelated glycinate should be be good. Here is the source I was talking about...

http://george-eby-research.com/html/depression-anxiety.html

Glutamate Toxicity

The worst mistake you can make is to use a magnesium compound called "magnesium amino acid chelate", or "chelated magnesium", or "magnesium chelate". Why? Many times these products are in fact magnesium glutamate or magnesium aspartate products and they will very likely make your depression worse. I don't know why laws exist to allow companies to label their products as a "chelate". That makes as much sense as labeling a product a "magnesium compound" or a "magnesium complex", since the words do not tell the full truth. I strongly suggest that you look over this list of legal aliases for the words "glutamate" or "aspartate".

chelate
glutamate
caseinate
textured protein
natural flavoring
yeast food
autolyzed yeast
hydrolyzed protein
hydrolyzed vegetable protein
yeast extract
hydrolyzed yeast
natural chicken or turkey flavoring
spices, and
modified food starch
Any time you find a magnesium compound that contains the above words in any kind of description, watch out! It will likely make you much more depressed than if you did nothing at all, since all of these words may (or may not) mean that glutamate and/or aspartate is the main ingredient in the product. The reason I bring this up is that a man from England bought and used a product labled "Magnesium Chelate" and got much sicker. This has also occured in the United States (very common) and Canada, and I suspect elsewhere too. When I researched it, I found the product to contain the magnesium complex of a modified food starch (glutamate). Needless to say, it made him much, much sicker. He barely survived since it very greatly worsened his depression and suicidal tendency. You have been warned as loudly as I can scream this warning! Here is more on glutamtate and aspartate.


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## Opiman (Aug 8, 2011)

The Professor said:


> The one thing I'm unclear about is that magnesium is considered a NMDA receptor antagonist! All of the other substances in this category are harmful to the brain so I don't see how magnesium isn't too. I'm probably way off on this, but from what I understand only 1/20 of the magnesium gets into your brain so that is what makes it safer than the others... I'm really not sure though, does anyone know?


No no no.. In a nutshell..

The brain tries it's best to maintain homeostasis (chemical balance). When you introduce a drug (amphetamine), it throws off this balance. The brain has several mechanisms by which it becomes aware of imbalances such as this. In the case of neurotransmitters, ie dopamine and serotonin, this mechanism is an influx of Ca+ ions. These ions signal the brain to release less dopamine and serotonin, restoring the balance. NMDA antagonists indirectly block this influx of Ca+ ions via another mechanism (glutamate), but the result is that the brain is not "aware" of any chemical imbalance. Magnesium is just another NMDA antagonist, similar to Memantine, and is just as harmless.

The reason Memantine is effective in "treating" Alzheimers is that glutamate just happens to have implications in learning and memory. From what I understand (and I'm not sure about this), the brain eventually (in a matter of weeks) upregulates another chemical downstream of glutamate (or perhaps glutamate itself?), restoring learning and memory function to it's previous (and even enhancing it according to some), but leaves the inhibition of Ca+ ions in place, allowing for tolerance prevention.

But no, NMDA antagonists are not in the least a bad thing.


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## Xande (Jul 18, 2011)

The Professor said:


> hmm... chelated glycinate should be be good. Here is the source I was talking about...
> 
> http://george-eby-research.com/html/depression-anxiety.html


Thanks! Yeah it just seems like author was saying to avoid chelated magnesium, since most of them are magnesium aspartame or gluatmate, of course I only skimmed your post.

But yeah, I heard magnesium glycinate is one of the best forms of magnesium. Also great sleep aid for me lol.


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## The Professor (Jul 31, 2011)

Opiman said:


> No no no.. In a nutshell..
> 
> The brain tries it's best to maintain homeostasis (chemical balance). When you introduce a drug (amphetamine), it throws off this balance. The brain has several mechanisms by which it becomes aware of imbalances such as this. In the case of neurotransmitters, ie dopamine and serotonin, this mechanism is an influx of Ca+ ions. These ions signal the brain to release less dopamine and serotonin, restoring the balance. NMDA antagonists indirectly block this influx of Ca+ ions via another mechanism (glutamate), but the result is that the brain is not "aware" of any chemical imbalance. Magnesium is just another NMDA antagonist, similar to Memantine, and is just as harmless.
> 
> ...


I don't understand how it isn't harmful according to this... Try to explain again. I need to put more thought into this.

http://en.wikipedia.org/wiki/NMDA_receptor_antagonist

So are you saying in the case of rasing any type of neroutransmitter, the brain releases Ca+ ions?

And I have a bad habit of reading user posts instead of scholarly sources but what do you think of this (the answer):

Q:
I heard here and on another set of forums magnesium was a nmda antagonist? I searched pubmed for 'magnesium nmda' and 'magnesium nmda antagonist' and found thousands of results, browsed a few pages randomly and found nothing.

Is this true?

I was also wondering if, being an nmda ant., it would potentiate opiates? I know DXM does, but does it due this because it's an nmda antagonist, or is some other method of action responsible for its potentiating opiates?

A:
"Well, yes. It's definatly true. But you can't really exploit that fact for recreational uses. Normally, your brain is under a very high level of Mg2+ blockade. Like, the concentration of Mg2+ needed to block 50% of NMDA receptor mediated currents is around the 20µM level. But in your brain, there's gonna be a concentration of around 1mM. So most of the channels are blocked by Mg2+.

The thing is, the Mg2+ NMDA receptor channel blockade is voltage dependent, so when ther neuron gets excited (depolarized), it kicks the Mg2+ out of the channel. But it can't kick Ketamine out, so thats why K gets you high and your magnesium multivitamin wont."


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## Opiman (Aug 8, 2011)

Drugs aren't by nature "bad". The negative effects some drugs exhibit are what make them dangerous. To look at it another way..

You say oranges are bad for you.
I explain how oranges work. How the acids and vitamins contained in them effect your body.
You say you don't understand how oranges aren't bad for you.

Well you can't just assume everything is bad for you without evidence.That just puts everything in the world into two categories:
Things that are bad for you and things that have not yet been shown to be bad for you.

You can see, this is a very negative way to live your life. I definitely would not recommend it.

Either way, I would advise reading the wikipedia article on Memantine at the very least. It does a decent job explaining what the drug does if you can grasp the whole Ca+/glutamate concept.

You can also read this post. It's basically a better/more in depth explanation of what I wrote in the last post.


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## crayzyMed (Nov 2, 2006)

Opiman said:


> Drugs aren't by nature "bad". The negative effects some drugs exhibit are what make them dangerous. To look at it another way..
> 
> You say oranges are bad for you.
> I explain how oranges work. How the acids and vitamins contained in them effect your body.
> ...


Agreed


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## euphoria (Jan 21, 2009)

The Professor said:


> hmm... chelated glycinate should be be good. Here is the source I was talking about...
> 
> http://george-eby-research.com/html/depression-anxiety.html
> 
> ...


That guy's a bit of a loon if you ask me. Magnesium deficiency sure can exist but it's not like it's THE cause of all mental illness, nor should it be megadosed like he advises. Just because it relieves symptoms doesn't mean magnesium deficiency was the cause - magnesium has an antidepressant effect, and this would be stronger even beyond doses that simply restore deficiency. It's like saying because lithium treats mania, lithium deficiency is the cause of mania. I haven't read his site properly in a while however.

Magnesium probably helps tolerance but you'd do better taking something like memantine for a stronger NMDA antagonism, and limiting magnesium intake to reccommended supplemental levels. And on the topic of memantine, keep the doses reasonable. It's indicated at 5-20mg per day for Alzheimer's. Who knows what side effects could become apparent in huge doses. Perhaps it could wreck the bladder like ketamine, and psychosis is a known side effect that'd likely be dose-dependent.


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## The Professor (Jul 31, 2011)

euphoria said:


> That guy's a bit of a loon if you ask me. Magnesium deficiency sure can exist but it's not like it's THE cause of all mental illness, nor should it be megadosed like he advises. Just because it relieves symptoms doesn't mean magnesium deficiency was the cause - magnesium has an antidepressant effect, and this would be stronger even beyond doses that simply restore deficiency. It's like saying because lithium treats mania, lithium deficiency causes mania. I haven't read his site properly in a while however.
> 
> Magnesium probably helps tolerance but you'd do better taking something like memantine for a stronger NMDA antagonism, and limiting magnesium intake to reccommended supplemental levels. And on the topic of memantine, keep the doses reasonable. It's indicated at 5-20mg per day for Alzheimer's. Who knows what side effects could become apparent in huge doses. Perhaps it could wreck the bladder like ketamine, and psychosis is a known side effect that'd likely be dose-dependent.


Yeah I agree with you. I was mostly just using it to find out what the best kind of magnesium is. I think he's right about that (gycinate), idk though.

Although, I remember reading somwhere that 50% of all americans are lactose intolerant and don't even know it, and this causes magnesium deficiency or something. I'm not saying it's from the magnesium that could be causing problems but mabe something that the dairy causes??? I'm going dairy free for a while to see if anything changes. It makes sense though... I read this book that was saying how dumb and unnatural it is to drink milk from a cow. We are the only mammals who drink milk after we are at the nursing age, and it's not even human milk it's froma cow! And all those got milk ads that say how healthy it is is put out by the gov't... I believe as a way to subsidize the industry. It contains (added) Vitamin D and calcium and a little protein... big deal! right?

But do you know the answer to my question about NMDA receptor antagonistS? from the wikipedia page it seems as though the effects are harmful and some of them are used as street drugs. Am I wrong?


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## euphoria (Jan 21, 2009)

The Professor said:


> But do you know the answer to my question about NMDA receptor antagonistS? from the wikipedia page it seems as though the effects are harmful and some of them are used as street drugs. Am I wrong?


Magnesium has a natural mild blocking effect on the NMDA receptor, but it's kind of different to actual NMDA antagonist drugs. I doubt dietary/supplemental magnesium could reach high enough levels, but IV magnesium probably could cause some sort of dissociative effect. NMDA receptor antagonist drugs aren't very dangerous in low amounts but high doses cause psychosis, and in ketamine's case, prolonged use causes bladder damage. High doses may also cause brain damage.


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## The Professor (Jul 31, 2011)

euphoria said:


> Magnesium has a natural mild blocking effect on the NMDA receptor, but it's kind of different to actual NMDA antagonist drugs. I doubt dietary/supplemental magnesium could reach high enough levels, but IV magnesium probably could cause some sort of dissociative effect. NMDA receptor antagonist drugs aren't very dangerous in low amounts but high doses cause psychosis, and in ketamine's case, prolonged use causes bladder damage. High doses may also cause brain damage.


This is my hypochondraism talking but how can something that is harmful in higher doses not be somewhat harmful in lower doses... I mean proportionately to the amount taken? Maybe it has never been _proved_ to cause damage but I don't see how it wouldn't.


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## Opiman (Aug 8, 2011)

The Professor said:


> This is my hypochondraism talking but how can something that is harmful in higher doses not be somewhat harmful in lower doses... I mean proportionately to the amount taken? Maybe it has never been _proved_ to cause damage but I don't see how it wouldn't.


Can you please link me *one* study that shows memantine to be harmful in higher doses? Just one? No? That's because there isn't one. It does not exist. Again, you're going into this with the same "everything in the world is bad for you despite lack of any evidence otherwise" mentality, and to be honest, it's f*cking ridiculous. The same argument can be used against pretty much anything and it makes just as much sense is it does here.

Maybe orange juice has never been _proved_ to cause damage but I don't see how it wouldn't.

Maybe exercise has never been _proved_ to cause damage but I don't see how it wouldn't.

Maybe breathing has never been _proved_ to cause damage but I don't see how it wouldn't.

Hell, with this mentality, I don't see how you manage to force yourself to get out of bed every morning with the constant fear that everything you encounter on a daily basis is in some way deadly, despite the fact that there is no evidence whatsoever to support any such notion.

Oh and by your logic, household Tylenol should be considered exceedingly lethal as it has been shown to cause liver failure and *DEATH* in just 5x the recommended therapeutic dose.

And just for your personal enlightenment, Dextromethorphan (DXM), the active ingredient in most cough syrup, is also an NMDA antagonist and at high doses has been shown at high doses to induce dissociative effects liken to PCP. Yet people don't seem to be avoiding cough syrup like the plague do they?

Most drugs WILL kill you at high enough doses. In fact, I can't think of any drugs that are completely harmless and benign regardless when taken at stupid high doses. But that isn't what we're discussing here.

In case you didn't understand the first two (three?) time I explained this,

Memantine is completely and utterly harmless when taken at the doses recommended here. And yes, the lack of a single study proving, or even hinting or suggesting otherwise does, in fact, *prove* this to be the case.

I am done with this topic. You can choose to believe whatever you want, and at this point I don't care. Any logical, rationally thinking person would look at the evidence presented to them and the overabundance of evidence all around that the vast majority of people you've been in contact with have pointed out to you, and choose to believe it. But I can tell at this point that you will, most likely, stick to your preconceived notions about the dangers of Memantine rather than heed the evidence presented to you by the scientific community as a whole.


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## The Professor (Jul 31, 2011)

Opiman said:


> Can you please link me *one* study that shows memantine to be harmful in higher doses? Just one? No? That's because there isn't one. It does not exist. Again, you're going into this with the same "everything in the world is bad for you despite lack of any evidence otherwise" mentality, and to be honest, it's f*cking ridiculous. The same argument can be used against pretty much anything and it makes just as much sense is it does here.
> 
> Maybe orange juice has never been _proved_ to cause damage but I don't see how it wouldn't.
> 
> ...


Well... like I said, I am a hypochondriac. It's a very tough way to live, please you don't need to tell me. What caused me to have this is problem is when I was "under the influence" of paxil, I decided to (it caused me to) combine and overdose on two extremely dangerous substances. Paxil was terrible for me and looking back on what I did while on it has caused me to have panic attacks and is what caused my current hypochodraism towards medications/chemicals. Do you think I don't know my mentality is ridiculous? Hypochondraism is a very powerful disorder.

And by the way, at high doses or in high amounts, breathing and exercise are harmful.

And I don't take household tylenol anymore (by my logic)... or anything with acetaminophen (this was in one of the things I took while on paxil)

All I'm looking for is an explanation about the wikipedia page that I posted on NMDA receptors... but I guess the "scientific community" doesn't have a direct answer.



> And just for your personal enlightenment, Dextromethorphan (DXM), the active ingredient in most cough syrup, is also an NMDA antagonist and at high doses has been shown at high doses to induce dissociative effects liken to PCP. Yet people don't seem to be avoiding cough syrup like the plague do they?


Yes this is my point! DXM is a very serious chemical that can cause damage and at very high doses, olney's lesions. Beleive it or not, there _are_ many people who avoid it like the plague, not just hypochondriacs either, but rather people who don't beleive man made chemicals are necessary to solve a cough. But my question is, how does magnesium differ from DXM in the fact that they are both NMDA receptor antagonists?



> Most drugs WILL kill you at high enough doses. In fact, I can't think of any drugs that are completely harmless and benign regardless when taken at stupid high doses. But that isn't what we're discussing here.


This is exactly why I seek to avoid drugs whenever I can. Unfortunately I may need them for SA and ADD, which is why I'm being so difficult.



> Memantine is completely and utterly harmless when taken at the doses recommended here. And yes, the lack of a single study proving, or even hinting or suggesting otherwise does, in fact, *prove* this to be the case.


The *lack* of a study does not *prove* anything! The only things it _proves_ is that we may or may not know enough yet.


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## Opiman (Aug 8, 2011)

Seems I forgot this is an anxiety forum..

If lack of evidence showing otherwise doesn't prove Memantine is harmless, please tell me what would. Nothing. There isn't a way to prove anything is harmless. The only way to show something is harmless is by demonstrating a lack of harm. You can never prove something is _incapable_ of causing harm, because really, anything can be harmful if abused. Water can be harmful if abused. You can only demonstrate that something has not caused harm thus far when used in a specific way, and is unlikely to do so with continued usage.

I personally don't use cough syrup, as I deem it unnecessary. Not specifically because I consider low dose DXM dangerous. And olney's legions have only been shown in studies with mice. Years of observation of use in humans has shown nothing similar.

Another problem with your logic is your assumption that since two drugs are of the same class of chemicals, they must have similar effects and side effects. I certainly don't see people going and getting retarded off of Memantine. When was the last time you heard of somebody tripping on Memantine? Never. It doesn't work.

Memantine and Ketamine aren't just two drugs with identical effects that happen to have slightly different chemical structures and different names. They're two completely different drugs that happen to effect the same type of receptor, but in completely different ways with completely different effects.

Something else I think you don't realize is that Ketamine, DXM, PCP, etc all antagonize NMDA receptors, but that isn't what makes them dangerous. Quoted from the Wiki article, these are DXM's other properties:


Uncompetitive NMDA receptor (PCP site) antagonist (Ki = 7,253 nM).[18][19][20][21]
σ1 and σ2 sigma receptor agonist (Ki = 205 nM and 11,060 nM, respectively). In a comparative investigation of dimemorfan, dextromethorphan and dextrorphan in mouse cells, dextromethorpan binds with relatively high affinity to Sigma-1 receptors and with very low affinity to Sigma-2 receptors.[18]
α3β4-, α4β2-, and α7-nACh receptor (Ki = in the μM range) antagonist. Dextromethorphan binds to nicotinic receptors in frog eggs (Xenopus oocytes), human embryonic kidney cells and mouse tissue. It inhibits the antinociceptive (pain killing) action of nicotine in the tail-flick test in mice, where mouse tails are exposed to heat, which makes the mouse flick its tail if it feels pain.[22][23][24]
μ-, δ-, and κ-opioid receptor agonist (Ki = 1,280 nM, 11,500 nM, and 7,000 nM, respectively).[25]
SERT and NET blocker (Ki = 23 nM and 240 nM, respectively).[3][25][26][27]
NADPH oxidase inhibitor.[28]

The only one of these that is relevant to Memantine is the first: NMDA antagonism. As you can see, there are a tirade of other properties by which other drugs cited [by you], which happen to be NMDA antagonists as well, harm the brain.

If you need further convincing:
Olney's legions only occur in lab rats administered DXM, Ketamine, PCP or Nitrous Oxide at moderate (recreational) doses
Olney's legions have NOT been observed in lab rats at low, therapeutic doses of DXM, Ketamine, PCP, or Nitrous Oxide
Olney's legions have NOT been observed in humans at any dose, much less at low, therapeutic doses of DXM, Ketamine, PCP, or Nitrous Oxide
Olney's legions have CERTAINLY NOT been observed in lab rats at moderate doses, in lab rats at low therapeutic doses, nor in humans at any dose, high, moderate or low (therapeutic) doses.

You're relying on not one, not two, but three logical fallacies to draw the conclusion you have.

In case you weren't aware, Olney's legions are not actually "holes" in the brain as the name leads one to believe. Rather, they're dilated mitochondria and endoplasmic reticulum that shrink back to normal size once the neurons are repaired (http://www.ncbi.nlm.nih.gov/pubmed/8140890)

And just to completely destroy your entire illogical argument, alcohol (ethanol) is an NMDA antagonist.

As a side note, Memantine has actually been shown to be neuroprotective


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## The Professor (Jul 31, 2011)

Okay thanks. Where do you learn all of this?

If there is no evidence that something is harmful, all it means it that *as far as we know* it is not harmful. For a normal person who doesn't read into things as much as I do, that might be enough to be considered proof, but I don't see it that way. How many times have there been thoughts about a certain thing based on tests, until a new test comes out that proves all of the old info wrong. Especially when regarding matters of the brain, which we know so little about.

To be clear, you are saying that the following statement on wikipedia is incorrect right?

"There is evidence that NMDA receptor antagonists can cause a certain type of neurotoxicity or brain damage referred to as Olney's Lesions in rodents, though such damage has never been observed in primates like humans."

According to you, it is not NMDA receptor antagonists that cause this... but rather, it is other properties of drugs that happen to also be NMDA RA's.

And another wikipedia page that backs up my worries is this... (the first few sentences about NMDA RA's)

http://en.wikipedia.org/wiki/Excitotoxicity


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## Opiman (Aug 8, 2011)

The Professor said:


> Okay thanks. Where do you learn all of this?
> 
> If there is no evidence that something is harmful, all it means it that *as far as we know* it is not harmful. For a normal person who doesn't read into things as much as I do, that might be enough to be considered proof, but I don't see it that way. How many times have there been thoughts about a certain thing based on tests, until a new test comes out that proves all of the old info wrong. Especially when regarding matters of the brain, which we know so little about.


Then I pose you the question: What would it take to convince you that something is in fact harmless? According to your definition of "proven" (which is different from a scientist's definition of "proven" as they prove things harmless all the time), it is effectively impossible to "prove" anything is harmless, as the only way to quantify harm is by demonstrating the presence of it. You can't prove that something_ doesn't exist_ because there is nothing to _shown_. But now we're getting into philosophy, which is beside the point. I really can't say anything more on this particular subject save repeat what I have already myself said. You can accept it or move on.



The Professor said:


> To be clear, you are saying that the following statement on wikipedia is incorrect right?
> 
> "There is evidence that NMDA receptor antagonists can cause a certain type of neurotoxicity or brain damage referred to as Olney's Lesions in rodents, though such damage has never been observed in primates like humans."


No that statement is true. Just lacking in detail. Notice it doesn't specify that _all_ NMDA antagonists cause neurotoxicity. Some do. Others don't. Not in the dosages we are discussing here.

Basic cell biology is about maintaining homeostasis. Too much of a chemical and the cell dies. Too much and the cell dies. Say a chemical, X, causes Y amount of atrophy above a concentration of Z. If you give the cell half that amount (Z/2) of the drug, it doesn't cause half the amount of atrophy (Y/2). The cell simply deals with the increased amount of chemical X. Compare it to filling a bucket. If a 8 Liter bucket overflows when filled 10 Liters of water, the bucket doesn't overflow half as much with 5 Liters of water. It just holds the extra water. The same concept applies to biology. Hopefully you understand now.



The Professor said:


> According to you, it is not NMDA receptor antagonists that cause this... but rather, it is other properties of drugs that happen to also be NMDA RA's.


No, that wasn't my point in bring up the other effects. The point was to show you that these drugs that are considered "dangerous" for reasons unrelated to the fact that they are NMDA antagonists. Many of the other properties of Ketamine, PCP, etc, are known to cause long term neurological impairment. You can't look at Memantine and DXM and say "hmm, they're both NMDA antagonists and so much have the same damaging effects on humans" when in reality DXM is a whole host of other things (sigma1 and sigma2 receptor agonist, alpha-3 beta-4 nicotinic receptor, alpha-4 beta-2 nicotinic receptor, alpha-7 nicotinic acetylcholine receptor, μ-, δ-, and κ-opioid receptor agonist, seretonin-transport blocker, norepinephrine-transport blocker, NADPH oxidase inhibitor) that make it dangerous. But the fact is that in the highly unlikely off chance that any NMDA antagonists do cause olney's legions in the brains of humans, human brains are incredibly efficient at repairing themselves. So unless you're abusing the **** out of these drugs, your brain will repair any of these legions before they become permanent damage. But again, none of this really even applies to humans in the first place as these legions only seem to occur in the brains of rats. I'll even quote wikipedia:



> The research into the relationship between rat brain metabolism and the creation of Olney's Lesions has been discredited and may not apply to humans, as has been shown with ketamine.


In other words, rat brains are very different from human brains and they way they deal with NMDA antagonists and metabolize them is very different from how humans do so.



The Professor said:


> And another wikipedia page that backs up my worries is this... (the first few sentences about NMDA RA's)
> 
> http://en.wikipedia.org/wiki/Excitotoxicity


I believe you misread this page.

Excitotoxicity is basically an overabundance of glutamage in the brain, caused by over-stimulation of NMDA receptors. This is what happens when you take amphetamine, but on a very small scale, causing a negligible (though this is subjective) amount of nerutoxicity. NMDA antagonists (Memantine) PREVENT NMDA receptors from being activated thus PREVENTING excitotoxicity. Hence Memantine's neuroprotective effects.


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## crayzyMed (Nov 2, 2006)

Once ive got my ability to focus back (ritalin doesnt help) i can contribute in this topic there's loads of info out there that can be discussed.


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