79 replies to this topic

[noos]

What about Magnesium for NMDA-antagonism/modulation?

http://en.wikipedia....ptor#Modulators

[scarredforlife]

What about Magnesium for NMDA-antagonism/modulation?

http://en.wikipedia....ptor#Modulators

 

It's so subtle, it won't help anyone with serious anxiety problems.

[Ezeon]

Great that Memantine is working for you. I've tried it for some time, but it did nothing for me. IMO, the α7 blockade is felt more strongly than the NMDA blockade. I believe this is also the reason some people don't like smoking while taking Memantine. Didn't affect me this way though.

 

Memantine was more potent in inhibiting α7* nAChRs than NMDA receptors; at -60 mV, the IC50 values for memantine were 0.34 and 5.1 μM [1]. The affinity for for α7* nAChRs is 15 times higher than for the NMDA receptor. However the blockade of α7s are voltage-dependent so that might factor into it as well.

 

[1] http://jpet.aspetjou...12/3/1195.short

[Frigo]

Hi!

 

I am also troubled by similar symptoms, and I also arrived at the conclusion that there is something funky going on regarding EAAT2/GLT-1.

 

I react negatively to most Glutamatergics. Most striking among those were the supposedly harmless Glutamine, which induces irritability, anger, paranoia, looping thoughts of hate, frontal headache, overheating and heart pain, even at laughtable doses (~500mg). I experienced this with D-Aspartic Acid as well, though to a much lesser degree.

 

I am curious, have you tried any kind of Glutamatergics, including Racetams, and experienced similar symptoms?

 

[satsumass]

DAA absoultey did that to me. Total rage, insanity, hate, paranoia. Glutamine energizes me and is friendly and i take 5-10g a day with no problem. Seems very odd that 500mg does that to you...very odd. You get dozens of grams a day with decent protein intake.

[FeelsNumbMan]

Hey OP, that's really good to hear. I have some Memantine with me from Ceretropic that I've ordered a long while back. I still haven't gave it a try yet. I heard that for the first week or so, you'll be experiencing some brain fog... That's probably one of the reasons why I didn't want to try it.

 

But I have tried ketamine, MXE, and DXM before. They didn't really seem to do much for how shitty I was feeling. Ketamine, maybe, but nothing *too* noticeable.

 

I have doubts for things working for me but I would also like to be optimistic. I've tried tianeptine once and I felt pretty out of it when I was working... I hated that. I don't want to feel out of it, especially at work. I never did tianeptine again, even though it was just a first time dose of 12.5mg.

 

-sigh- I hope there are things out there that I can try that would actually work for my feelings of anhedonia and apathy. I find it hard to socialize with people because I just don't care... I can't really bounce off their conversations because I don't even feel like I have anything interesting to say. Or I just think whatever I say isn't interesting, but there are a lot of things that doesn't interest me. That includes other people's conversations... but I just do it just because.

 

I wanted to try SJW this weekend... but maybe I should try memantine? Would it hurt to try both at the same time or would I just feel really really out of it because of the two? I also don't like having a reduced appetite and such either.

[Frigo]

DAA absoultey did that to me. Total rage, insanity, hate, paranoia. Glutamine energizes me and is friendly and i take 5-10g a day with no problem. Seems very odd that 500mg does that to you...very odd. You get dozens of grams a day with decent protein intake.

 

I can take Whey Protein shakes without any apparent problems, but it has other amino acids as well that can counteract it, for example Cysteine. Pure Glutamine screwed me up every time I have tried it.

Edited by Frigo, 11 July 2014 - 12:02 PM.

[Climactic]

Memantine is useful, but let's also consider bupropion extended-release at a dose of 150 mg with a possible later increase to 300 mg. Bupropion takes a few weeks for its metabolites to accumulate in the body at a steady state. It's an antidepressant and is reported to help with socialization. You can read about their specific effects on various receptors on Wikipedia. Two drugs have some similarities with regard to dopaminergic and anticholinergic effects. While memantine is useful for lowering glutamate receptor overactivation, bupropion offers no such luck - it in fact slightly increases the risk of a seizure by lowering its threshold.

 

Also consider extended-release 40 mg propranolol. It seems to slightly inhibit fear, or rather the fight vs flight response. Within a week people will find you happier. I would consider the safest of the three.

Edited by Climactic, 11 July 2014 - 02:27 PM.

[medievil]

Im preparing a new central memantine thread, did one years ago but the net is full of new anecdotes and some new interesting research came out so stay tuned guys.

[sparkk51]

Ive asked two psychiatrists for memantine to combine with amphetamines and they rejected it because it would be off-label. Is there anyway someone like me in the U.S. could get my hands on some good quality memantine?

 

[FW900]

Ive asked two psychiatrists for memantine to combine with amphetamines and they rejected it because it would be off-label. Is there anyway someone like me in the U.S. could get my hands on some good quality memantine?

 

 

It's not a controlled substance and you can import it online as an actual medication or buy it as a bulk chemical from domestic sources (e.g., Ceretropic).

 

Online pharmacies like ADC sell memantine but it is rather pricey and the dosages are much too high and will cause brain fog if they are your starting dose. Ceretropic sells it as a sublingual solution and the dosages are much lower (which is a good thing) than the prescription medication (Namenda/other). It would make more sense to start out with the sublingual solution so you can slowly, upwardly, titrate your memantine dose.

[Al Capacino]

Ive asked two psychiatrists for memantine to combine with amphetamines and they rejected it because it would be off-label. Is there anyway someone like me in the U.S. could get my hands on some good quality memantine?
 

I get mine from United pharmacies. It's an online pharmacy which appears to be based in Australasia somewhere. They ship international and prices very reasonable I think. In fact I think they are cheapest I've seen for certain things. I get buspar and wellbutrin from them too.

[neuralis]

Always Learning, how did you work up your dosage to current level? You said that you started on IR, did you notice any beneficial effects from it, or only from the ER formulation?

I just started taking memantine for social and general anxiety, as well for depression. I also suffer from terrible brain fog, I long suspect to be caused by glutamate over activity.

I took my first dose of 5mg IR and want to know how fast is it safe to up my dosage?

[sparkk51]

Wow, I've already received my Memantine solution from Ceretropics. Does anyone have any idea how I should store this stuff?

 

So, I've already received a solution of Memantine from Ceretropics. Does anyone know how I should store it?

 

[thereisway]

aLWAYS Learning .. . have yoou tried racetams before as coluracetam is anxyolitic?

[Mind_Paralysis]

 

NMDA-antagonism makes the brain forget. The depressive anxiety-inducing pathways are de-learned

 

It depends. In theory NMDA-antagonism should be considered anti-nootropic, and it is unnecessary with healthy individuals. However, some people experience too much NMDA activity, which is even worse, because it causes excitotoxicity (neuronal death). Also, there is a difference between full antagonists like Ketamine and DXM, and Memantine. Memantine is a partial antagonist and seems to eliminate only excessive glutamate without impairing normal receptor function.  

 

 

Quite correct. Highly, highly increased NMDA-activity has been discovered among sufferers of Alzheimers -disease, which was the original intended patient-group for Memantine. However, it was also found that it was insufficient - it actually seems like Memantine is too WEAK to stop the high glutamate excitotoxicity that people with the disease has. 0_0

 

When you're already losing your ENTIRE mind, memories and all, NMDA-manipulation might not be such a bad thing, after all.

 

And even though Alzheimers is one of the extremes of neurological diseases related to increased NMDA-activity, there are others as well - ADHD for instance.

 

Hence, enter: NITRO-Memantine!

 

http://en.wikipedia..../Nitromemantine

 

Nitromemantine is more powerful than Memantine, since it has a nitrate-group added to it, allowing Memantine to bind to a second site on the NMDA-receptors, hence, it theoretically lowers glutamate enough to even help Alzheimers-sufferers.

 

It's currently in testing, but it won't be on the market until a couple of years, probably.

 

It should also be noted... that the developers of nitro-mem, have also been testing it for other uses - primarily ADHD and Aspergers! : 0 As it would appear, Autism appears to have some pathophysiology shared not just with ADHD, but with several of the comorbid diseases that the two groups of NPD's share - namely learning-disabilities.

 

According to their findings - Nitromemantine may not just help ADHD, it could help those with Autism, DCD, Dyslexia, Dyscalculia, Dysgraphia and several other genetically inclined learning-disabilities.

 

Apparently... they're all the same thing, in one way or another. Which isn't odd, since genetic data seems to imply that metabotropic glutamate-network mutations are involved in many NPD's.

 

Here's the article about theoretical effect on ASD:
 

http://sfari.org/new...ism-mouse-model

 

 

In the new study, the researchers found that the drugs reverse the anxiety, repetitive behavior and abnormal social behavior seen in the mutant mice. They also alleviate the deficits in learning and memory.

The researchers plan to test these drugs in neurons generated from induced pluripotent stem cells derived from two individuals who have MEF2C mutations and autism.

 

There's already been some talk about Nitromemantine on the board, but not enough, IMHO. When the chemical formula for Nitromemantine is properly available, a group-buy should target this, as it could well be outstanding stuff for anyone with some form of NPD.

 

( neuro-psychiatric disease)

 

The fact that the OP noticed increased coordination fills me with quite some hope! =)

 

Coordination-problems and ADhD-PI is currently holding my evolution as an artist back, and if Memantine really does serve to affect more of the symptoms that I have, than normal medication, then that would be absolutely stellar.

 

 

aLWAYS Learning .. . have yoou tried racetams before as coluracetam is anxyolitic?

 

Would definitely be interesting to know. I happen to know that others with ADHD, that try racetams, can actually get brainfog, or they are simply highly ineffective, as a treatment for the memory-problems associated with ADHD.

 

GetOutofBox on this board, which had a great, great thread regarding ADD ( ADhD-PI, hypoactive, instead of HYPER-active) reported that Coluracetam was in essence USELESS for him.

That's what got him on the track of NMDA-antagonism actually, since he felt that Glutamate-agonists, seemed to worsen some of his symptoms.

 

This actually makes sense, because ADHD ( elevated NMDA-receptors, highly lowered dopamine-release ) is in many wasy a disease that works IN REVERSE of Schizophrenia ( lowered NMDA-receptors, highly elevated dopamine-release), and there is currently research into racetams as a con-commitant treatment for Schizophrenia - some of them apparently benefit GREATLY from both Aniracetam and Oxiracetam - which both increase NMDA-activity.

 

They were, accidentally, two of the compounds that GoB found to be UTTERLY useless for ADHD-PI.

 

All things considered, all of this makes sense.

 

Ketamine has long been used to induce psychotic states, in order to study them, and try to devise treatment for Schizophreniacs - and Ketamine shares a lot of its properties with Memantine. And ADHD-ers have low dopamine, while Schizo's have high dopamine. Amphetamine is POISON to Schizo's, but LIFES-BLOOD for ADHD-ers.

 

It all finally makes sense... when you just slam it all up there, on the drawing-board, and start drawing all the connecting lines.

Edited by Stinkorninjor, 20 July 2014 - 09:45 PM.

[VICREP]

I was on the memantine + Dextroamphetmine combo not to long ago, and slowly titrated my dose up to 10mg per day. I was on this dose consistently for around 1 month and couldn't cope with the constant lapse in memory, and dissociative feeling I was getting from the drug.

 

I couldn't imagine getting up to 20+mg of memantine daily.

 

I might try it again in a few months when my memory dose not have to be as sharp. I just can't see how something that antagonizes NMDA receptors and Nicotinic Acetycholine receptors could be taken daily without noticeable cognitive deficits.

[sparkk51]

I havent noticed anything from the memantine solution I got from Ceretropics. Im taking 10mg per day.

 

[Ames]

 

I'm also on 21mg, but would advise that initial namenda responses are typically VERY different than long term. Initially you are getting a ton of nicotinic and d2 action as you build up blood levels. I'm VERY interested in how you do long term. I've found long term for me it tends to lose some punch but whenever I decrease my dose I get a bit more unstable, more disnhibited, less able to focus and definitely more compulsive.

 

The more pertinent information would be whether you are above, at, or below pre-memantine baseline after you wean yourself off of memantine. Of course, taking amphetamines concurrently introduces a variable that makes your experience only significant to the informal consensus on memantine's effects while taking amphetamines. That's valuable too, but also different than speaking to responses to memantine-only medication.

 

 

It's really where pathologies like autism come from.  Autism covers a broad spectrum of misprogrammed epigenetic pathways that are abnormal and stable in their abnormality even years later.  These misprogrammings can become progressively maladaptive over time.

 

As an aside: I get this perspective, however it most often leads to looking toward methylation manipulation as therapy. I'm not sure why people focus on methylation abnomrailities as a treatable cause of autism. I agree that there is evidence for an epigenetc cause of autism,  however, there are proven grey matter volume abnormalities in individuals with ASD vs controls that methyl donors, and probably even gene therapy, could likely never hope to treat. In other words, mentioning the probable epigenetic cause of autism without mentioning permanent  morphological differences (not you, but in general) misleads the public in my opinion.

 

http://www.ncbi.nlm....les/PMC3201995/

 

 

Memantine is useful, but let's also consider bupropion extended-release at a dose of 150 mg with a possible later increase to 300 mg. Bupropion takes a few weeks for its metabolites to accumulate in the body at a steady state. It's an antidepressant and is reported to help with socialization. You can read about their specific effects on various receptors on Wikipedia. Two drugs have some similarities with regard to dopaminergic and anticholinergic effects. While memantine is useful for lowering glutamate receptor overactivation, bupropion offers no such luck - it in fact slightly increases the risk of a seizure by lowering its threshold.

 

Also consider extended-release 40 mg propranolol. It seems to slightly inhibit fear, or rather the fight vs flight response. Within a week people will find you happier. I would consider the safest of the three.

 

I see where you're coming from: that is from the perspective of ameliorating depression/anxiety by any means necessary that is supported in the clinically accepted pharmacy. That's as valid as it gets. I think, though, that what most people, who are looking toward memantine as a solution, are aiming for is a solution that is theoretically neuroprotective in nature. A marker for an effective substance, that would also fill the "do less harm" (if not be outright neuroprotective), is one for which there is little withdrawal. Additionally, some form of positive adaptation or upregulation in function would also be desired. I'm not saying that memantine necessarily fills this role very well, although some might argue that fact, I'm just attempting to articulate why someone might look to memantine for depression vs approved antidepressants.

Edited by golgi1, 25 July 2014 - 03:15 PM.

[neuralis]

Did anyone else notice increase in social anxiety when first started taking memantine?

[simone_no1]

Hi Chaps, thanks for excellent comments and research on Memantine. Any thoughts and/or experiences of combining Memantine with Concerta? I have seen some benefits from the latter in terms of attention - but also think it makes me less creative and cognitively adaptive. Any thoughts on overcoming these issues would be appreciated...

[AlwaysLearning]

Sorry I've been so reticent lately, I've had a lot going on including a move to a new city. I am happy to report that the antidepressant and anxiolytic effects are still going strong and I still seem to be using my new pathways. ^_^ I'll try to give a better response soon, but for now -

 

I've actually come across a paper or two indicating that magnesium actually blocks the activity of memantine. I haven't noticed a problem when I've taken magnesium while on memantine though.

 

I definitely titrated my dose. It took a month or two to get to the 28 mg XR dose. I started with IR and switched to XR. I've never taken it sublingually but that'd be pretty much the opposite of an extended release route, as it'd give you a quick spike and faster fall-off in plasma concentration. I can't speak to the effects in such a scenario from personal experience, but if you don't like them, don't take it sublingually. I also can't speak to the quality of the "memantine" obtained from internet sources - afaik there is no mainstream sublingual formulation so I'd be really wary of anything like that from the grey market. I have had good experiences with United Pharmacies though and I see they have "Ebixa" memantine as an oral solution, which might be absorbable sublingually.

 

My experience with Wellbutrin XR is that it increased my anxiety, and I felt as though it brought me close to panic attacks (though I never actually had one). Let's be clear though - there isn't one single kind of anxiety. We use that term to describe more than one neurological phenomenon, and I believe the anxiety that Wellbutrin caused was a different sort than I was used to. Also I should note that I was not taking Wellbutrin alone; it may well have synergized with Adderall XR and caffeine to produce that effect.

 

Again I must stress that if your problems do not have a glutamatergic etiology, memantine may have only negative effects for you! Do NOT rush to a high dose. DO consider it a diagnostic tool.

 

Regarding the commonality between the disorders mentioned - my money is still on immune-related pathology. All of those disorders are likely to involve inflammatory processes, and as I've mentioned, "neuroinflammation" is likely to affect glutamate regulation (among other things).

 

Simone - it sounds like what you're describing could involve overactivity in the anterior cingulate, which I suspect can be worsened by stimulants and alleviated by memantine. So YES, try combining them (at your own risk, of course - I assume no responsibility ).

[AlwaysLearning]

FYI, something else (very preliminary) to ponder, regarding ADHD and glutamate. Some interesting background is provided as well.

 

Association between the GRM7 rs3792452 polymorphism and attention deficit hyperacitiveity [sic] disorder in a Korean sample

 

The purpose of this study was to investigate the association between the ionotropic and glutamate receptors, N-methyl D-asparate 2A (GRIN2A) and 2B (GRIN2B), and the metabotropic glutamate receptor mGluR7 (GRM7) gene polymorphisms and attention-deficit hyperactivity disorder (ADHD) in Korean population.

→ source (external link)

 

The metabotropic glutamate receptor subtype 7 rs3792452 polymorphism is associated with the response to methylphenidate in children with attention-deficit/hyperactivity disorder.

 

The purpose of this study was to investigate the association between the metabotropic glutamate receptor subtype 7 (mGluR7) gene (GRM7) polymorphism and treatment response to methylphenidate in Korean children with attention-deficit/hyperactivity disorder (ADHD).

METHODS:
We enrolled 175 medication-naïve children with ADHD in an open-label 8 week trial of methylphenidate. The participants were genotyped and evaluated using the Clinical Global Impressions (CGI) Scale and the parent version of the ADHD Rating Scale-IV (ADHD-RS) before and after treatment.

RESULTS:
After the 8 week course of methylphenidate, children with the GRM7 rs37952452 polymorphism G/A genotype had a more pronounced response rate to the treatment than did children with the G/G genotype according to the ADHD-RS scores (72.2% vs. 55.4%, respectively; p=0.011) and the more stringent standard of combined ADHD-RS and CGI-Improvement (CGI-I) scores (50.0% vs. 35.3%, respectively; p=0.044).

CONCLUSIONS:
The present study suggests that the GRM7 rs37952452 polymorphism may play a role in the treatment response to methylphenidate in children with ADHD. Further studies to evaluate the association between glutamate genes and treatment response to methylphenidate in children with ADHD, including a replication of our findings using a control or comparative group in a larger sample, are warranted.

→ source (external link)

------------------

 

 

Another interesting article regarding depression and glutamate (also touching on cadherins):

 

Genome-wide association scan of trait depression

Abstract
Background
Independent of temporal circumstances, some individuals have greater susceptibility to depressive affects, such as feelings of guilt, sadness, hopelessness, and loneliness. Identifying the genetic variants that contribute to these individual differences can point to biological pathways etiologically involved in psychiatric disorders.

Methods
Genome-wide association scans (GWA or GWAS) for the Depression scale of the Revised NEO Personality Inventory (NEO-PI-R) in community-based samples from a genetically homogeneous area of Sardinia, Italy (N = 3,972) and from the Baltimore Longitudinal Study of Aging in the US (N = 839).

Results
Meta-analytic results for genotyped or imputed single nucleotide polymorphisms (SNPs) indicate that the strongest association signals for trait depression were found in RORA (rs12912233; p= 6 × 10−7), a gene involved in circadian rhythm. A plausible biological association was also found with SNPs within GRM8 (rs17864092; p = 5 × 10−6), a metabotropic receptor for glutamate, a major excitatory neurotransmitter in the central nervous system.

Conclusions
These findings suggest shared genetic basis underlying the continuum from personality traits to psychopathology.

→ source (external link)

Edited by AlwaysLearning, 19 August 2014 - 05:47 AM.

[zeropoint]

 Always Learning (so true,so true) I have been using low dose DXM like you are using memantine, with similiar benefits with the added advantage of easier availability(OTC cough syrup). I have some memantine  though that I have been meaning to try...thought 2.5mg.-5mg. to start? I believe it has a longer half-life also....Interesting thread by the way....

[Frigo]

[...]

 

Excessive NMDA activation and antagonism can coexist!

 

Quinolinic acid and Kynurenic acid are made at different steps of the same Kynurenine pathway. Insulin resistance and immune activation can and do increase Kynurenine and its metabolites.

 

Although there is insufficient research in this direction, Schizophrenia might have issues with Quinolinic acid as well, not just Kynurenic, especially judging from the cognitive difficulties. So other mental diseases might have simply different levels of Quinolinic and Kynurenic acid at play, rather than being the complete opposite of Schizophrenia. So treatment should not be mutually exclusive either. I heard Memantine and Amphetamine of all things used for the negative effects of Schizophrenia.

Edited by Frigo, 21 August 2014 - 11:19 PM.

[Mind_Paralysis]

Yeah, since I wrote that, I've actually started thinking there's something to that... The negative symptoms of Schizophrenia definitely seem like something pretty similar to ADHD-PI/Slow Cognitive Tempo - brain-fog, bad attention, low motivation, anxiety, etc.

 

Fairly interesting, the on the one hand, clear dichotomy, but on the other hand, similarity as well. Tell me, there is a connection between Bipolar and Schizophrenia, right? But what kind of connection? Is it just the high dopamine-levels? In bipolar, those go up and down, and sometimes they're depressed and SCT-like, but sometimes they're incredibly active and dynamic, with almost enhanced mental abilities, and the next moment - impaired.

Is it the same for Schizophrenia? Do the dopamine-levels fluctuate, or are they always high? That seems to be the primary difference between ADHD and schizo and bipolar btw - our symptoms are remarkably stable, in their negativity, that is.

 

Tell me more about the negative symptoms of Schizophrenia... how do they even exist?

 

Now I got to thinking about Quinolinic acid... does that function as an agonist of glutamate? Instead of an NMDA-antagonist, like Kynurenic acid.

 

It would be highly interesting to do a far-reaching study on quinolinic and kynurenic acid among ADHD-patients, Schizophreniacs, and neurotypicals. What are the differences, indeed...?

BTW, what do you figure would be the result of supplementing Kynurenic acid, in small doses, on those with ADHD? I'm actually crazy enough, that I started considering that as a treatment of ADHD.

[rmuniz]

Hi everyone!

 

Does anyone Still using memantine ? How's it going ?

 

I've started (5mg) 4 days ago. When should I expect to effect ?

 

best regards

[zeropoint]

  Our memory got all shot to heck from the memantine.....we remember nothing. That's how it works, you forget all your problems and are happy! (just kidding)

[eon]

benadryl does the same thing doesn't it?

 

  Our memory got all shot to heck from the memantine.....we remember nothing. That's how it works, you forget all your problems and are happy! (just kidding)

 

[eon]

very interesting thread that I had to bump it. I read about Ketamine being in the same class of drug as memantine (NMDA antagonist). I think PCP is as well but that has more sides. To OP, are you still taking memantine?