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Unanswered memantine questions


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#1 winston

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Posted 24 June 2010 - 02:12 AM


I'm thinking of using memantine allow me to stay on benzos for longer stretches. Would it work to take it for a week, take memantine for a day to lower tolerance quickly, then start on the benzos again, then memantine... etc etc?
I know it can lower the time that tolerance takes to get back to zero, but I'm not sure on just how strongly it does this.

Also, which effects of memantine are subject to tolerance after a while? In one thread, some people said they developed a tolerance, but it wasn't clear weather memantines anti-dependent effect on other drugs was still working just as well.

#2 krillin

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Posted 24 June 2010 - 04:49 AM

Am I the only person for whom memantine doesn't work? The muscarinic stimulation was way more intense than the NMDA antagonism, so 5 mg/day actually increased muscle tension from dust activating my TRPs. (I am apparently very sensitive to cholinergics. Sulbutiamine has the same effect.) I tried to counter it with trihexyphenidyl, but trihexy mainly goes to the brain, while memantine makes a pit stop in the lungs (PMID: 9639292) on its way there, so I got bronchoconstriction. Rimantadine is now the only NMDA antagonist in my stack, and it doesn't do anything without both felodipine (or nimodipine) and gabapentin. Clonidine augments it, and safens NMDA antagonists according to Olney's papers. I used to have 100 mg/day amantadine in there too (much cheaper than rimantadine, but can't go above 100 mg without it depleting my catecholamines), until I learned about how it damages the cornea. L-dopa does that too, so it looks like a dopamine effect so rimantadine should be safe.

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#3 graatch

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Posted 24 June 2010 - 06:56 AM

>I'm thinking of using memantine allow me to stay on benzos for longer stretches

I recently wrote this in a Mind & Muscle thread (http://www.mindandmu...showtopic=42354):

"I wouldn't count on memantine doing much to change the desensitization of GABA receptors (and upregulation of excitatory systems) that generally characterizes extended use of GABAnergic agents, nor to stave off associated issues of dependence and withdrawal. I'm not aware of any mechanism that would have it do so.

Although it should help ease the withdrawal syndrome from a GABAnergic drug to some extent (a la alcohol withdrawal or benzodiazepine withdrawal) by inhibiting excitatory rebounds of glutamate, which are a component of the syndrome's toxicity.

It could indeed help to preserve the reactivity and sensitivity of dopaminergic systems (the dopamine response to a given dose of GABAnergic sedative, as well as dopaminergic rebounds as the drug recedes."


"With regards to memantine, there's really no reason at all it would affect this. The mechanism of memantine's downstream affect on opioid and certain specific dopaminergic systems is something that has been drawn out by research and analysis -- whereas the distinct subset of receptor sites related to GABA-A that benzodiazepines cling to is not on the current map."


That said, in the thread there was however one anecdotal report where the person believes that memantine allowed him to use alprazolam with diminished tolerance, for whatever that may be worth.

#4 medievil

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Posted 24 June 2010 - 07:11 AM

its actually well documented that NMDA antagonists prevent tolerance to the hypnotic effects of ethanol and benzo's, however another study found no effect on tolerance to the anxiolytic effect of benzo's.

http://www.ncbi.nlm..../pubmed/8971413
http://www.ncbi.nlm..../pubmed/9399331
http://www.ncbi.nlm..../pubmed/8341715
(look for my old thread for further referenes regarding ethanol and other drugs).

Copy of a post of me on another forum:

While updating my NMDA antagonist thread i accidently deleted the benzo section. There were 3 studies showing that NMDA antagonist prevent dependence and tolerance to the sedative effect of benzo's, however there was also a study showing that NMDA antagonists dont prevent tolerance to the anxiolytic effect.

And then ive read 3 reports about memantine for benzo tolerance, one ive got in a PM (saying memantine reversed tolerance to the anxiolytic effect), the other one says this:

I took Alprazolam for 3 years, then went through accidental cold-turkey withdrawal because the local pharmacies weren't carrying any (happens where I live occasionally, sucky country/city). I experienced severe withdrawal symptoms including paranoia and transient psychosis but soon I got again on Alprazolam and thankfully didn't have a seizure. During that period I was completely tolerant to 2 mg Alprazolam's both sedative and anxiolytic effects.

Since I started taking Memantine, the tolerance was reversed somewhat and 1 mg was anxiolytic and practical enough for social anxiety disorder. 2 mg was very effective sedative. Tolerance didn't develop any further from this point on.


And then there's that report about rebound anxiety.

Personally i'm inclined to beleive that memantine does in fact prevent tolerance to the anxiolytic effects too (beleiving the anecdotal reports), the reason why that wasnt the case in that seperate rat study is imo because they used a differend NMDA antagonist then memantine, ive seen that they can behave differendly (for example recently saw a study showing NMDA antagonist 1 prevented both tolerance by repeated dosing, and tolerance induced by social defeat, however memantine only prevented tolerance to repeated dosing and not that induced by social defeat) so differend NMDA antagonists can behave differendly wheter thats the reason i dont know, but thats my gues about whats going on.

Edited by medievil, 24 June 2010 - 07:16 AM.

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#5 graatch

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Posted 24 June 2010 - 07:16 AM

Am I the only person for whom memantine doesn't work? The muscarinic stimulation was way more intense than the NMDA antagonism, so 5 mg/day actually increased muscle tension from dust activating my TRPs. (I am apparently very sensitive to cholinergics. Sulbutiamine has the same effect.) I tried to counter it with trihexyphenidyl, but trihexy mainly goes to the brain, while memantine makes a pit stop in the lungs (PMID: 9639292) on its way there, so I got bronchoconstriction.


I'm sensitive to some symptoms associated with muscarinic excitation also (muscle tension, racing thoughts), and sometimes have gotten them from memantine initially or when I accidentally take more than usual. For me though they fade after a few days at a constant dose, and were not much of a problem when I titrated slowly to my target dose (increasing by increments of 2.5mg/day every 3 days, up to 40mg/day split into two doses).

My inclination is to link muscarinic effects from memantine to nicotinic antagonism, which if selective classically will result in concomitant muscarinic stimulation -- to an extent the two acetylcholine receptor types compete for activity -- this effect desensitizes fully after some time in the memantine research, which also seems common with the nicotinic receptors in general. This would bring things in line, neatly in terms of timeframe, with my and others' experience of early negative cognitive effects (and things like muscle tension) that fade after an adaptation period.

However, the adaptation may not be as smooth for you, or fail to occur!

I do certainly doubt that you are the only person who might have lingering problems with this area of side effects.

Rimantadine is now the only NMDA antagonist in my stack, and it doesn't do anything without both felodipine (or nimodipine) and gabapentin. Clonidine augments it, and safens NMDA antagonists according to Olney's papers. I used to have 100 mg/day amantadine in there too (much cheaper than rimantadine, but can't go above 100 mg without it depleting my catecholamines), until I learned about how it damages the cornea. L-dopa does that too, so it looks like a dopamine effect so rimantadine should be safe.


You might look at acamprosate (Campral) one of these days. Like memantine, unlike e.g. ketamine or DXM, it may be categorized as an "uncompetitive" antagonist of NMDA, with activity that usefully scales to NMDA stimulation. The poster andrewb, one of the first people (he posted on the dr-bob forums) to document in detail conjecture and his experiences with memantine applied to the purpose of maintaining sensitivity to limbic psychostimulant effects, eventually used, instead of 30mg memantine daily, 10mg with 333mg acamprosate (Campral) taken twice daily, with equal considerable success.

I don't know how acamprosate might differ from memantine's potential for muscarinic activity, but it's worth a look perhaps.
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#6 graatch

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Posted 24 June 2010 - 07:16 AM

edit: double post

Edited by graatch, 24 June 2010 - 07:46 AM.


#7 graatch

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Posted 24 June 2010 - 07:45 AM

Whoops. My left-click is screwed up, sorry about that.

Medievil, thanks for those, it seems there may be more to this than I thought and you are definitely making me re-evaluate. With regards to the third abstract, it appears that an NMDA antagonist diminished the toxicity of benzodiazepine withdrawal during the period that toxic symptoms appear in the rat, which is not surprising and certainly something an NMDA antagonist should do. Note this does not speak to benzodiazepine tolerance in terms of diminished effect however.

The second abstract and first contain some more interesting data, the second being the strongest, although I have to remain skeptical at this point, due to contradictory data in other research (which you mention) and some confusing things or perhaps caveats found in the abstracts as well. It is important to get clarification on certain terms and what partial tolerance constitutes in this study ... as well as 'learned and unlearned tolerance', which is an unusual description. I hope to get a hold of the full texts of these.

Personally i'm inclined to beleive that memantine does in fact prevent tolerance to the anxiolytic effects too (beleiving the anecdotal reports)


If we're making predictions, I think ultimately I may have to settle for a more complex view of this issue, because even if dopaminergic mechanisms is the only thing about benzodiazepine effects that memantine touches, then that would still change benzodiazepine tolerance, because none of these systems stand alone. Mesolimbic dopamine is certainly intimately related to one other major system with depressant tendencies, the endogenous opioid system.

(Hence my interest in descriptors like partial tolerance)

But I think it's important, healthy to retain doubt in these cases ... not until there's more information. This goes for memantine and amphetamine as well as memantine and benzodiazepines.

the reason why that wasnt the case in that seperate rat study is imo because they used a differend NMDA antagonist then memantine, ive seen that they can behave differendly (for example recently saw a study showing NMDA antagonist 1 prevented both tolerance by repeated dosing, and tolerance induced by social defeat, however memantine only prevented tolerance to repeated dosing and not that induced by social defeat) so differend NMDA antagonists can behave differendly wheter thats the reason i dont know, but thats my gues about whats going on.


It's certainly the case that NMDA antagonists can differ vastly and memantine especially has a number of unusual properties, although this doesn't say anything specific.

Edited by graatch, 24 June 2010 - 07:59 AM.


#8 bobman

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Posted 25 June 2010 - 05:30 AM

Memantine is not an "NMDA antagonist" competitve or non-competitive, because it does not bind to glycine or glutamate sites. Its NMDA-antagonizing mode of action is by blockade of pre-synaptic CA2+ entry. So yes, while it won't cause glutamergic neurotoxicity (since it decreases voltage-gated glutamte release by inactivating CA2+ evoked NMDAR activation), it absolutely will evoke a homeostatic response leading to increase in NMDAR binding sites. Tolerance & withdrawal effects will follow, although there's no way to tell how severe. It will probably mimic lamotrigine or riluzole tolerance and withdrawal effects (both of those mainly inhibit NA+ evoked NMDA excitation/extracellular glutamate).

#9 penisbreath

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Posted 25 June 2010 - 08:16 AM

M Tolerance & withdrawal effects will follow, although there's no way to tell how severe. It will probably mimic lamotrigine or riluzole tolerance and withdrawal effects (both of those mainly inhibit NA+ evoked NMDA excitation/extracellular glutamate).


Tolerance to what though? Memantine's tolerance prevention? Its anti-obsessional mechanism?
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#10 medievil

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Posted 25 June 2010 - 01:05 PM

Memantine is not an "NMDA antagonist" competitve or non-competitive, because it does not bind to glycine or glutamate sites. Its NMDA-antagonizing mode of action is by blockade of pre-synaptic CA2+ entry. So yes, while it won't cause glutamergic neurotoxicity (since it decreases voltage-gated glutamte release by inactivating CA2+ evoked NMDAR activation), it absolutely will evoke a homeostatic response leading to increase in NMDAR binding sites. Tolerance & withdrawal effects will follow, although there's no way to tell how severe. It will probably mimic lamotrigine or riluzole tolerance and withdrawal effects (both of those mainly inhibit NA+ evoked NMDA excitation/extracellular glutamate).


I personally didnt experience any sign of withdrawal after taking 10mg for a month in my first trial. And from reading anecdotal reports i'm not the only one.

Memantine HCl is a low to moderate affinity uncompetitive NMDA antagonist that did not produce any evidence of drug-seeking behavior or withdrawal symptoms upon discontinuation in 2,504 patients who participated in clinical trials at therapeutic doses


But on the other hand:

Two cases of discontinuation syndrome following cessation of memantine.

Although memantine is widely used and generally considered safe, an abrupt cessation of memantine may result in discontinuation syndrome that can be distressing and result in decline of natural course. We report two patients who developed significant behavior disturbance after abrupt cessation of memantine. Although re-trial of memantine improves these symptoms, more additional drugs may be required to achieve previous status. Therefore, abrupt cessation of memantine should be prudent and require cautious follow up.

Either way, the above seems to be very rare (only 2 reports) and i doubt any rebound is a big issue in anyone that isnt suffering from alzheimer.

I beleive thorsten here reported tolerance to the stimulating rewarding seeking effects (wich i personally never experienced) however regarding its OCD and tolerance reduction properties i havent seen anyone reporting a tolerance.

Edited by medievil, 25 June 2010 - 01:08 PM.


#11 bobman

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Posted 25 June 2010 - 07:19 PM

M Tolerance & withdrawal effects will follow, although there's no way to tell how severe. It will probably mimic lamotrigine or riluzole tolerance and withdrawal effects (both of those mainly inhibit NA+ evoked NMDA excitation/extracellular glutamate).


Tolerance to what though? Memantine's tolerance prevention? Its anti-obsessional mechanism?


Essentially your brain will need to figure out how to operate with massively increased CA2+ evoked signals. Memantine inhibits one of the main excitatory responses in the human brain. To make up for that, your body will increase the amount of receptors, in hopes that the lower levels of extracellular CA2+ will be made up for by more potential binding sites. When you go off memantine, all bets are off, as now you probably have normalized levels of extracellular CA2+, AND more receptors. Your body has to manage the situation or you'll have massive glutamate toxicity. The severity of withdrawal of course depends on dose and duration. It is no surprise that some people do not exhibit any withdrawal symptoms (the regulatory response upon washout is not enough of a disruption to be noticed).

Also, there is some new research showing that antidepressants, neuroleptics, and anti-epileptics cause epigenetic changes in the brain. So it is possible that you no longer have the same levels of gene expression after taking memantine. No one knows if these changes are fixable, or even whether all of them need to be fixed, but some research shows that gene expression can be controlled by thought alone, and of course diet and exercise changes gene expression as well.

Both of those factors can contribute to withdrawal issues.

Edited by bobmann, 25 June 2010 - 07:23 PM.


#12 Logan

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Posted 25 June 2010 - 07:29 PM

M Tolerance & withdrawal effects will follow, although there's no way to tell how severe. It will probably mimic lamotrigine or riluzole tolerance and withdrawal effects (both of those mainly inhibit NA+ evoked NMDA excitation/extracellular glutamate).


Tolerance to what though? Memantine's tolerance prevention? Its anti-obsessional mechanism?


Essentially your brain will need to figure out how to operate with massively increased CA2+ evoked signals. Memantine inhibits one of the main excitatory responses in the human brain. To make up for that, your body will increase the amount of receptors, in hopes that the lower levels of extracellular CA2+ will be made up for by more potential binding sites. When you go off memantine, all bets are off, as now you probably have normalized levels of extracellular CA2+, AND more receptors. Your body has to manage the situation or you'll have massive glutamate toxicity. The severity of withdrawal of course depends on dose and duration. It is no surprise that some people do not exhibit any withdrawal symptoms (the regulatory response upon washout is not enough of a disruption to be noticed).

Also, there is some new research showing that antidepressants, neuroleptics, and anti-epileptics cause epigenetic changes in the brain. So it is possible that you no longer have the same levels of gene expression after taking memantine. No one knows if these changes are fixable, or even whether all of them need to be fixed, but some research shows that gene expression can be controlled by thought alone, and of course diet and exercise changes gene expression as well.

Both of those factors can contribute to withdrawal issues.


While I am still taking a few medications, I am hoping that my current fast will help my brain heal and recover from all the medication trials and chronic stress/depression/anxiety of the past 2 years. When I feel well enough, I will begin to exercise as I used to and hopefully this will continue to maintain the health of my brain.

#13 bobman

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Posted 25 June 2010 - 07:55 PM

M Tolerance & withdrawal effects will follow, although there's no way to tell how severe. It will probably mimic lamotrigine or riluzole tolerance and withdrawal effects (both of those mainly inhibit NA+ evoked NMDA excitation/extracellular glutamate).


Tolerance to what though? Memantine's tolerance prevention? Its anti-obsessional mechanism?


Essentially your brain will need to figure out how to operate with massively increased CA2+ evoked signals. Memantine inhibits one of the main excitatory responses in the human brain. To make up for that, your body will increase the amount of receptors, in hopes that the lower levels of extracellular CA2+ will be made up for by more potential binding sites. When you go off memantine, all bets are off, as now you probably have normalized levels of extracellular CA2+, AND more receptors. Your body has to manage the situation or you'll have massive glutamate toxicity. The severity of withdrawal of course depends on dose and duration. It is no surprise that some people do not exhibit any withdrawal symptoms (the regulatory response upon washout is not enough of a disruption to be noticed).

Also, there is some new research showing that antidepressants, neuroleptics, and anti-epileptics cause epigenetic changes in the brain. So it is possible that you no longer have the same levels of gene expression after taking memantine. No one knows if these changes are fixable, or even whether all of them need to be fixed, but some research shows that gene expression can be controlled by thought alone, and of course diet and exercise changes gene expression as well.

Both of those factors can contribute to withdrawal issues.


While I am still taking a few medications, I am hoping that my current fast will help my brain heal and recover from all the medication trials and chronic stress/depression/anxiety of the past 2 years. When I feel well enough, I will begin to exercise as I used to and hopefully this will continue to maintain the health of my brain.



Good luck. I'm not trying to scare you. If the medications are helping you get through a tough time, and you know you cannot do without them, then taking them is your only option, and the right decision. I can tell that once you're able you'll reduce the medication load. I doubt that even a few years of non-neurotoxic medications (meaning that they don't directly result in brain death) will cause any permanent cognitive debilitation.

#14 FunkOdyssey

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Posted 25 June 2010 - 08:53 PM

Good luck. I'm not trying to scare you. If the medications are helping you get through a tough time, and you know you cannot do without them, then taking them is your only option, and the right decision. I can tell that once you're able you'll reduce the medication load. I doubt that even a few years of non-neurotoxic medications (meaning that they don't directly result in brain death) will cause any permanent cognitive debilitation.


There's also the possibility that whatever epigenetic changes occur are part of the drugs therapeutic effect, and may leave you better off than you started. I wouldn't assume that simply because changes in gene expression take place that these are automatically negative or undesirable.

Edited by FunkOdyssey, 25 June 2010 - 08:53 PM.

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#15 bobman

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Posted 25 June 2010 - 11:51 PM

Good luck. I'm not trying to scare you. If the medications are helping you get through a tough time, and you know you cannot do without them, then taking them is your only option, and the right decision. I can tell that once you're able you'll reduce the medication load. I doubt that even a few years of non-neurotoxic medications (meaning that they don't directly result in brain death) will cause any permanent cognitive debilitation.


There's also the possibility that whatever epigenetic changes occur are part of the drugs therapeutic effect, and may leave you better off than you started. I wouldn't assume that simply because changes in gene expression take place that these are automatically negative or undesirable.


I didn't say they were, although it is quite evident that unless the costs of the changes are known it is better to abstain from anything impacting your genome. That's besides the point, both the epigenetic changes and upregulated NMDAR expression are likely mechanisms for memantine tolerance and withdrawal symptoms. The question was whether memantine could induce dependency, and it absolutely can, by means similar to other voltage-dependent, cation-inhibitory drugs. Also reduction in extracellular glutamate by lamotrigine leads to increased GABA levels (~20-30% at ~10x therapeutic steady state plasma levels), and associated changes in GABA receptor expression, which indicates another possible target for memantine dependency.

#16 penisbreath

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Posted 26 June 2010 - 02:25 AM

Essentially your brain will need to figure out how to operate with massively increased CA2+ evoked signals. Memantine inhibits one of the main excitatory responses in the human brain. To make up for that, your body will increase the amount of receptors, in hopes that the lower levels of extracellular CA2+ will be made up for by more potential binding sites. When you go off memantine, all bets are off, as now you probably have normalized levels of extracellular CA2+, AND more receptors. Your body has to manage the situation or you'll have massive glutamate toxicity. The severity of withdrawal of course depends on dose and duration. It is no surprise that some people do not exhibit any withdrawal symptoms (the regulatory response upon washout is not enough of a disruption to be noticed).

Also, there is some new research showing that antidepressants, neuroleptics, and anti-epileptics cause epigenetic changes in the brain. So it is possible that you no longer have the same levels of gene expression after taking memantine. No one knows if these changes are fixable, or even whether all of them need to be fixed, but some research shows that gene expression can be controlled by thought alone, and of course diet and exercise changes gene expression as well.

Both of those factors can contribute to withdrawal issues.


Memantine is a drug that helped me a lot when I trialled it for a month, and one I plan to return to soon. While obviously not your intention, your post has scared me a little. Would an increase in NMDAR sites be an ongoing problem post-discontinuation? Or is it more an issue with respect to withdrawal?

#17 penisbreath

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Posted 26 June 2010 - 07:36 AM

edit: double post


On an unrelated note, graatch I briefly wrote about some working memory issues I'd been having on M&M, which you were nice enough to reply to. I've just been wondering - do you think memantine would have a positive effect on working memory? I can't really find a definitive answer from studies.

#18 medievil

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Posted 26 June 2010 - 09:54 AM

Essentially your brain will need to figure out how to operate with massively increased CA2+ evoked signals. Memantine inhibits one of the main excitatory responses in the human brain. To make up for that, your body will increase the amount of receptors, in hopes that the lower levels of extracellular CA2+ will be made up for by more potential binding sites. When you go off memantine, all bets are off, as now you probably have normalized levels of extracellular CA2+, AND more receptors. Your body has to manage the situation or you'll have massive glutamate toxicity. The severity of withdrawal of course depends on dose and duration. It is no surprise that some people do not exhibit any withdrawal symptoms (the regulatory response upon washout is not enough of a disruption to be noticed).

Also, there is some new research showing that antidepressants, neuroleptics, and anti-epileptics cause epigenetic changes in the brain. So it is possible that you no longer have the same levels of gene expression after taking memantine. No one knows if these changes are fixable, or even whether all of them need to be fixed, but some research shows that gene expression can be controlled by thought alone, and of course diet and exercise changes gene expression as well.

Both of those factors can contribute to withdrawal issues.


Memantine is a drug that helped me a lot when I trialled it for a month, and one I plan to return to soon. While obviously not your intention, your post has scared me a little. Would an increase in NMDAR sites be an ongoing problem post-discontinuation? Or is it more an issue with respect to withdrawal?

While memantine can upregulate NMDA receptors, AFAIK this is only limited and there isnt an ungoing tolerance, also memantine is known for its lack of withdrawal.

Edited by medievil, 26 June 2010 - 09:59 AM.


#19 chrono

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Posted 26 June 2010 - 10:17 PM

On an unrelated note, graatch I briefly wrote about some working memory issues I'd been having on M&M, which you were nice enough to reply to. I've just been wondering - do you think memantine would have a positive effect on working memory? I can't really find a definitive answer from studies.

I'm wondering about this as well. This study in MS patients found "significant declines in some variables associated with verbal learning and memory that improved upon medication withdrawal." But most people here have said that they don't notice impairments once they're used to a given dose. Either it was an interaction specific to MS patients, only certain people are affected, or it's the kind of problem difficult to detect without the aid of objective testing.

#20 FunkOdyssey

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Posted 26 June 2010 - 10:42 PM

On an unrelated note, graatch I briefly wrote about some working memory issues I'd been having on M&M, which you were nice enough to reply to. I've just been wondering - do you think memantine would have a positive effect on working memory? I can't really find a definitive answer from studies.

I'm wondering about this as well. This study in MS patients found "significant declines in some variables associated with verbal learning and memory that improved upon medication withdrawal." But most people here have said that they don't notice impairments once they're used to a given dose. Either it was an interaction specific to MS patients, only certain people are affected, or it's the kind of problem difficult to detect without the aid of objective testing.


Also remember it was dose-related and only occurred once they reached 30mg, higher than is typically used (20mg).

#21 penisbreath

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Posted 27 June 2010 - 01:34 AM

On an unrelated note, graatch I briefly wrote about some working memory issues I'd been having on M&M, which you were nice enough to reply to. I've just been wondering - do you think memantine would have a positive effect on working memory? I can't really find a definitive answer from studies.

I'm wondering about this as well. This study in MS patients found "significant declines in some variables associated with verbal learning and memory that improved upon medication withdrawal." But most people here have said that they don't notice impairments once they're used to a given dose. Either it was an interaction specific to MS patients, only certain people are affected, or it's the kind of problem difficult to detect without the aid of objective testing.


I think it is dose-dependent. Some people also metabolize the drug at different rates. I've seen reports where certain bipolar patients were using 5mg b.i.d. with success for disease-related cognitive impairment.

#22 krillin

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Posted 01 July 2010 - 06:07 AM

My inclination is to link muscarinic effects from memantine to nicotinic antagonism, which if selective classically will result in concomitant muscarinic stimulation -- to an extent the two acetylcholine receptor types compete for activity -- this effect desensitizes fully after some time in the memantine research, which also seems common with the nicotinic receptors in general. This would bring things in line, neatly in terms of timeframe, with my and others' experience of early negative cognitive effects (and things like muscle tension) that fade after an adaptation period.

However, the adaptation may not be as smooth for you, or fail to occur!

I think memantine has independent muscarinic effects. Bupropion's nicotinic antagonism makes me stupid but not crushed by my muscles, while memantine causes the crushing but doesn't affect my cognition.

#23 John Barleycorn

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Posted 02 July 2010 - 07:27 AM

I think memantine has independent muscarinic effects. Bupropion's nicotinic antagonism makes me stupid but not crushed by my muscles, while memantine causes the crushing but doesn't affect my cognition.


I get jaw clenches which I simply attributed to the dopamine agonism. Muscarinic effects would presumably include salivation, no?

Personally, 5mg is way too dissociating for me. That's using everyone's favourite Indian brand.

#24 penisbreath

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Posted 04 July 2010 - 12:02 PM

"Cognitive effects of memantine in postmenopausal women at risk of dementia: a pilot study.
Wroolie TE, Kenna HA, Williams KE, Powers BN, Holcomb M, Lazzeroni L, Rasgon NL.

Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA 94305-5723, USA.

BACKGROUND: To determine the effects of memantine on cognition in a normal population of postmenopausal women with putative risk factors for Alzheimer's disease (AD) using a built-in control for the genetic risk factor for AD (apoE-epsilon4 status). METHODS: A prospective, open-label, 6-month pilot medication trial with memantine and follow-up after discontinuance conducted at the Center for Neuroscience in Women's Health, Stanford University School of Medicine. Neuropsychological data were collected on 22 community-dwelling postmenopausal women (11 apoE-epsilon4 carriers and 11 apoE-epsilon4 non-carriers) with at least one putative risk factor for AD. RESULTS: ApoE-epsilon4 status was not a significant predictor of change in neuropsychological performance. Changes associated with memantine treatment for entire sample included significant declines in some variables associated with verbal learning and memory that improved upon medication withdrawal. A positive medication effect was noted with executive functions and possibly category fluency. Trend-level improvements were seen in motor dexterity of the non-dominant hand and maintained even after drug discontinuance. CONCLUSIONS: Treatment with memantine appeared to have differential effects on cognitive performance in a population of women with putative risk factors for AD. ApoE-epsilon4 carrier status did not account for observed changes in cognition.

PMID: 18705678 [PubMed - indexed for MEDLINE]"


can anyone account for this study? i know one poster Pike mentioned that the verbal learning interference went away after 6 weeks, but this study was conducted over 6 months. they do refrain from mentioning the dose they used ...

#25 krillin

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Posted 05 July 2010 - 02:42 AM

I get jaw clenches which I simply attributed to the dopamine agonism. Muscarinic effects would presumably include salivation, no?

Two possible explanations for lack of salivation: either memantine concentrates too much in the brain for that to happen, or my sensitized brain and lungs have lower thresholds than my salivary glands.

Dopamine appears to make my jaw happy. It felt the best when endorphins from LDN would work, but endorphins don't work for me if there's too much NMDA activity from reacting to dust or microbial VOCs. It'll also feel better if I'm feeling dopamine from antimuscarinics or amantadine. (But the former is too impairing, while the latter only works for a week until catecholamine depletion or tolerance sets in.) Serotonin from an SNRI or SSRI made it way worse: raw carrots hurt to chew and I'd get jaw grinding even when awake.

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#26 John250

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Posted 20 June 2018 - 05:06 AM

Ok wait wait wait! Memantine is used to help the tapering process of amphetamines, opiates, nicotine and benzodiazepines but now I’m reading that there can actually be Memantine withdrawl?




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