# NMDA receptor agonists. A new direction in treating DP DR.



## rob35235 (Feb 21, 2009)

I have come to the conclusion that doctors and researchers don't give a fuck about us, since so little research has gone into DP and DR. They are mainly concerned about the mental processes which cause a ruckus to the observer, such as acting out associated with bipolar, shizophrenia, etc etc. Where as we mostly act "normal" but inside are tortured beyond comprehension!!! We have to figure this shit out on our own, people.

Now, to understand my next proposal, first you must familiarize yourself with the NMDA receptor of the brain: http://en.wikipedia.org/wiki/Nmda_receptor

Good, now that you're an expert on the NMDA receptor, let's move on to NMDA receptor _Antagonists_ (google: antagonist definition if you're not sure what that means): Dextromethorphan (found in some cough syrups), ketamine (that white powder that stupid people snort), and the infamous PCP. All Extremely bad for the DP/DR sufferer, obviously, as these drugs are actually known for their dissociative effects. NMDA recptor antagonists on wiki: http://en.wikipedia.org/wiki/NMDA_receptor_antagonist
Also, did you know nitrous oxide (dental gas) is an NMDA receptor antagonist, with dissociative effects, as well?

Hmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmm.

Agonist is the polar opposite of antagonist, the following excerpt is from wikipedia.org:
Agonists

Activation of NMDA receptors requires binding of glutamate or aspartate (aspartate does not stimulate the receptors as strongly).[12] In addition, NMDARs also require the binding of the co-agonist glycine for the efficient opening of the ion channel, which is a part of this receptor.

D-serine has also been found to co-agonize the NMDA receptor with even greater potency than glycine. D-serine is produced by serine racemase, and is enriched in the same areas as NMDA receptors. Removal of D-serine can block NMDA-mediated excitatory neurotransmission in many areas. Recently, it has been shown that D-serine is synthesized mostly by neurons, indicating a role for neuron-derived D-serine in NMDA receptor regulation.

In addition, a third requirement is membrane depolarization. A positive change in transmembrane potential will make it more likely that the ion channel in the NMDA receptor will open by expelling the Mg2+ ion that blocks the channel from the outside. This property is fundamental to the role of the NMDA receptor in memory and learning, and it has been suggested that this channel is a biochemical substrate of Hebbian learning, where it can act as a coincidence detector for membrane depolarization and synaptic transmission.

OK somebody figure this shit out, I gotta run...but I'll be back. find drugs which are agonists


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## Claymore (Jun 13, 2009)

rob35235 said:


> Dextromethorphan (found in some cough syrups)


This drug right here is what put me in DP in the first place after I drank a 4oz bottle of Robotussin DM (Which Dextromethorphan is the main ingredient and gives you an EXTREMLY dissociative high) and mixed a little pot with it and went into a phychotic rant I was so high that I had to go to the hospital. The Dextromethorphan high is DP, it feels exactly like DP because thats what it is I guess.


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## rob35235 (Feb 21, 2009)

Claymore said:


> rob35235 said:
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> 
> > Dextromethorphan (found in some cough syrups)
> ...


Oh my god, how cool is that? (I don't mean cool that you have DP, but I damn well think I/we must be on to something. We must find a way to agonize the NMDA receptors. What drug will do this, though. This CANNOT be ignored


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## Claymore (Jun 13, 2009)

rob35235 said:


> Claymore said:
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> 
> > rob35235 said:
> ...


I agree we need to find an agonist to these receptors. How could we find one though?


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## rob35235 (Feb 21, 2009)

Here is a little reading I'm doing right now http://www.medhelp.org/posts/Schizophre ... how/952637
Something to do with glutamate..........

although we don't have schizophrenia, we probably have a similar pathology, I found this article very interesting (wonder why we haven't heard about this all over the news)? http://www.theage.com.au/national/cause ... -b6tb.html


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## rob35235 (Feb 21, 2009)

OK I get it now, NMDA receptors are a type of glutamate receptor


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## Claymore (Jun 13, 2009)

I found this page it may help. Go to the top of the page to "disorders research" and DP is on the list.

http://www.neurotransmitter.net/migraineglutamate.html


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## rob35235 (Feb 21, 2009)

Nice find...from that page..
"Neurochemical findings have suggested possible involvement of serotonergic, endogenous opioid and *glutamatergic NMDA* pathways"

I assume, though am not certain, serotonergic is related to serotonin, ie-SSRI drugs, and the opioid thing is related to that naloxitine (sp?) experiement that was going with some people here on the board.

Also, "Overall, novel therapeutic approaches are clearly needed to help individuals experiencing this refractory disorder."
Yeah...no kidding!


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## Guest (Aug 19, 2009)

You guys are *awesome*! Keep up the good work 8)

Check: Niacin :mrgreen:


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## rob35235 (Feb 21, 2009)

ThoughtOnFire said:


> You guys are *awesome*! Keep up the good work 8)
> 
> Check: Niacin :mrgreen:


Niacin? That's vitamin B3.....can you explain your thoughts?


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## voidvoid (Sep 5, 2008)

CAN WE GET *ABSENTIS* AND *COMFORTABLY NUMB* IN THIS THREAD AS SOON AS POSSIBLE THANKS

GREAT WORK YOU GUYS


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## Guest (Aug 19, 2009)

rob35235 said:


> ThoughtOnFire said:
> 
> 
> > You guys are *awesome*! Keep up the good work 8)
> ...


Oh, it has been known to treat Schizophrenia. I just thought I'd throw it out there. I don't know what it does in the brain.


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## Claymore (Jun 13, 2009)

I found this as well Rob. A page with possible treatments of psychiatric disorders, once again if you look at the list, DP is under dissociative disorders. Here it is.

http://psychcentral.com/disorders/


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## comfortably numb (Mar 6, 2006)

The NMDA recept is a tricky little bugger more then abit difficult to understand for sure. It's pretty complicated compared to say the serotonin receptor for instance.

I hate to dissapoint anyone here but a NMDA receptor agonist is pretty damn neurotoxic. The cure would be worse then the disease for sure. NMDA itself which is a amino acid is a excitotoxin. In other words anything that acts as a NMDA receptor agonist is bad shit.


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## Absentis (Jul 10, 2007)

Inzom said:


> CAN WE GET *ABSENTIS* AND *COMFORTABLY NUMB* IN THIS THREAD AS SOON AS POSSIBLE THANKS


Reporting for duty!

The matter of the role of NMDA receptors in DPD isn't a new one. It recevied a good discussion in Dr. Simeon's book _Feeling Unreal_, and provids the rationale for using lamotrigine. As mentioned previously in this thread, ketamine is an NMDA receptor antagonist, and produces dissociation. Pretreatment with lamotrigine prevents dissociation, and was investigated in treating DPD for that reason, having limited success.

In terms of similar treatments, I believe the one thing that wasn't mentioned in the book is the use of l-glycine, an amino acid. IIRC, a user of this forum posted that Dr. Simeon had prescribed (or was recommending) that her patients try using this amino acid on top of whatever else they were taking. A similar amino acid is d-serine. Both of which act together with glutamate to activate a receptor. The reason they aren't examined very closely in neurobiology texts is because enough of them are produced by the body (non-essential amino acid) to always fulfill their role as a co-agonist.

(As an aside, I recently had a friend who experienced his first episode of psychosis and was lucky enough to be living in a big city in which there is a treatment center devoted solely to treating individuals who have experienced psychosis for less than 6 months (before schizophrenia can be officially diagnosed.) I researched the literature on using animo acid and even spoke with the clinic's director who had recently finished a study on the use of several amino acids as adjunct therapy. All-in-all, I'm not particularly enthusiastic about the efficacy of using amino acids to treat mental disorders.)



comfortably numb said:


> I hate to dissapoint anyone here but a NMDA receptor agonist is pretty damn neurotoxic. The cure would be worse then the disease for sure. NMDA itself which is a amino acid is a excitotoxin. In other words anything that acts as a NMDA receptor agonist is bad shit.


I disagree that NDMA receptor agonists are inherently neurotoxic, as some are endogenous and play a crucial role in memory (and probably other things that don't immediately come to mind.) I'll certainly concede that they are excitatory, but not necessarily excitotoxic. As with any neurotransmitter, too much can be harmful; take an abundance of serotonin which can lead to serotonin syndrome as an example. If you have a particular reason, however, for saying that NMDARAs are inherently dangerous, I'd like to get the reference from you and take a look.

I think the most important aspect of this discussion is to emphasize the importance of avoiding NMDAR antagonsts (like DXM and ketamine) as they _certainly_ exacerbate dissociative phenomena.


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## Claymore (Jun 13, 2009)

Absentis said:


> (like DXM and ketamine) as they _certainly_ exacerbate dissociative phenomena.


Your not KIDDING!!!!!!!! Only after I did DXM did I get DP and ill tell you one thing, the DXM high IS THE >EXACT< SAME AS DP. A DXM high feels, looks, and anything else you can think of JUST LIKE DP!!!! THAT STUFF IS EVIL!!!!! :evil: If anyone wants to know what DP feels like who has never experienced it before, just drink 2 or 3 oz of Robotussin DM, and you'll know EXACTLY what DP is like. I drank a whole 4oz bottle and got the high (that kinda scared the crap out of me!!!) and the next day I realized that a lot of the DXM high wasn't wearing off, and ive had DP every sense. Absentis, do you think the DXM could have caused some kind of brain damage?


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## Absentis (Jul 10, 2007)

Claymore said:


> Absentis, do you think the DXM could have caused some kind of brain damage?


You're not going to like my answer, but it would be irresponsible of me to lie, so I will tell you the truth: It is possible that DXM causes brain damage. This particular type of brain damage is called Olney's lesions, and they are the result of NMDAR antagonist neurotoxicity.[1] They are the result of high doses of dissociative drugs, particularly drugs like ketamine, PCP, and the drug you used, DXM.

However! Before you become scared that you have permanently damaged your brain, consider this: The tests that scientists conducted on NMDAR antagonist neurotoxicity were done on *rats*, not humans. To date, there have been no studies that have conclusively demonstrated Olney's lesions in humans. Since no one has looked at the brains of humans immediately after administering these drugs, [it isn't known] whether or not the physical neuronal injury occur.[2] Anecdotal information from speaking with friends and reading on the internet points towards the accumulation of vast cognitive impairment in individuals who constantly abuse DXM at high doses.

So if you got high on DXM once or twice, any potential damage would be negligible because your brain has amazing methods of coping with neuron and glial damage through recruitment, reorganization, and compensation. It may have triggered a latent predisposition to DPD, but I can't comment for sure in your case as I don't know if you've identified your experience with DXM as the major trigger for your DP/DR. (Edit: Re-reading your post made me realize that you identify DXM as having caused you DP. In this case, I have no information, sorry.)

Now, for some better news that is more applicable to the thread: During the course of fact-checking my post, I came across a list of substances that are purported to reduce or prevent the neurotoxicity associated with NMDAR antagonists: GABA-A agnoists, anticholinergics, benzodiazepines, barbiturates, and agonists at alpha-2 adrenergic receptors, such as clonidine. Of this list, benzodiazepines are already widely used in the treatment of DPD, but I've never heard of clonidine being tried. Perhaps that's something we should find out if anyone has had experience with.

In conclusion, if you did get brain damage from DXM, it was probably minor (unless you abused it, or took massive doses) and your brain has been able to compensate for it and maintain proper cognitive and executive functioning. If you have further questions, or wish to discuss more of this, feel free to post again or send me a pm.

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1. Olney JW et al. NMDA antagonist neurotoxicity: mechanism and prevention. _Science_ 254(5037):1515-8, 1991 Dec 6.
2. Olney JW. Personal Communication. 28 January 2002. Published on _erowid.org._


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## Claymore (Jun 13, 2009)

Absentis said:


> Claymore said:
> 
> 
> > Absentis, do you think the DXM could have caused some kind of brain damage?
> ...


Well first off, thank you Absentis for awnsering.  Ok, ill tell you exactly what happened. I started smoking pot around age 12 (Im 19 now) and it started just every once in a while with a new friend that id met at school. Then at around 14 and 15, I was smoking almost every day. Never bothered me except for a couple times where I smoked too much and paniced. But no DP (I didnt even know this existed at this time). Then I became psychologically addicted to pot and at the same time my step-father and I could not get along and I had many health issues that hindered me in school. I had hyperthyroidism, a B-12 defficiancy for which I took shots for every month, I had (and let me see if I can spell this right) pernicious anemia which is a slow heartbeat due to the med (Toperol XL) that my doc had me on for the thyroid issue. The whole time still smoking pot heavily. And because my average heartbeat was 30 beats a minute, I would just kinda pass out at my desk in school and I was constantly tired so they took me off the Toperol and slowly my heart came back to normal. Finally in the later months of age 15, me and my step-dad just could not get along because of his bad verbal abuse. So I moved to my grandmother's house. My 25 year old cousin also stayed there because he couldnt hold down a job because he was highly addicted to DXM. He would drink 5 to 6 bottles of Robotussin DM every night and play computer games all night. I got a job at Mcdonalds and when I got my first paycheck, I bought a half oz of some strong pot and brought it home. Well, one night I became curious of DXM and I wanted to know what the high felt like (now keep in mind id never heard the word dissociation or DP). So I asked my cousin how much it took to get him high the first time he did it and he said 1 4oz bottle. So I said, Ill try it one time. So he gave me a 4oz bottle and I drank it and about an hour later the high kicked in and I thought it was pretty cool, I felt a little strange but still pretty cool. So we stayed up all night playing war games on the PC and watching Pulp Fiction. So the next day I was off work and that night when my cousin came home he had his DXM and I still had my pot so I lit up my pipe and got a little high and said, screw it , after this high wears off im gonna try that DXM one more time. So he gives be another 4oz bottle and I drank it and waited about the same amount of time but this time, it wasnt doing hardly anything, I just felt like I had a little alcohol buzz so instead of drinking more I said, screw this so I pulled out my pipe and took about 8 good hits. Well, about 60 seconds later I experienced something horrible that I can only describe as the highest id ever been, it was a nightmare. I thought I was going to die and I was walking through the house yelling and crying. Long story short, I called the ambulance and went to the hospital. I had bad DP for about 2 years after that. At first I thought I was going crazy but I found out what DP was so I dealt with it. By this time my mom left my step-dad and I moved back in with her. Well after about 2 years, it started to disapate and I was only on 50mg of Zoloft and I was getting out a lot. So when the third year came, It was almost gone, it was barley noticable and I was VERY happy. Well in Febuary of this year, I went to visit my dad in Virginia and the guy he was staying with (and by the way I stopped doing any drugs after the first bout with DP) was a drug addict and he wanted to get high so I mentioned DXM because it was a cheap high. So we go to the store and buy an 8oz bottle of Robo DM and brought it to him and he just started chugging the bottle. He left about 2 oz in the bottle so I figured maybe that will give me a little buzz because I was really bored and nobody else wanted it so I drank it. And I didnt really expect it to do much since it was only 2 oz. So about 2 hours later it started getting me really high and I was thinking, "what the heck?it was only 2 oz!!!!". Well it scared me and I paniced again but didnt go to the hospital this time. Well, finally I was able to fall asleep. I woke up the next day with the DP stronger than ever and it hasnt lifted yet. Its even worse than the last bout because at least last time I didnt question my own existence. I knew I just had an ailment and I expected it to go away. But thats the whole story, I know it was a long one but, what do ya think? :|


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## York (Feb 26, 2008)

I think you got it from panicking... For some fucked up reason it doesn't take much anxiety for it to be triggered and stick with you. You've already experienced the symptoms becoming less severe at one point, right?


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## comfortably numb (Mar 6, 2006)

Ok i was putting it in black and white terms there. In small doses the co-agonist glycine is not toxic but in high doses it can cause cell death via excitotoxicity. But yes you are right they do play a role in learning and memory. So no NMDA is not straight out neurotoxic just like a antagonist at this site is not straight out neurotoxic. However drugs that are straight out NMDA agonists would be neurotoxic and much more so then a antagonist which in small doses are actually neuroprotective. Though this again is abit simplilistic.

I would give a better explaination of all this but my brain isint working that good today and my attension span at the moment is near zero. Plus it is not really needed for this discussion and explaining just how all this shit works is confusing. Even i don't understand a good bit of it.

Taking a NMDA antagonist while you suffer from dp/dr is no doubt a very bad idea. They are dissociatives afterall :roll: . DXM seemed to make mine better while i was high on it (or atleast it usually removed my anxiety) but it came back with a vengence the next day. Nitrous oxide made me feel better and had no effect when it wore off and i can't remember what PCP did besides majorly mess me up. DXM is sort of like alcohol in that way which is also a NMDA antagonist interestingly enough. In fact i think NMDA antagonism is one proposed mechanism by which alcohol causes it's neurotoxicity.

As for brain damage caused by DXM a single use isint going to cause any significant damage unless you take a shitload. Also the olneys lesions theory doesent hold true for humans but DXM certainly does do something with your brain after prologued use. All NMDA antagonists do to a certain extent. Ive seen some people who have used DXM at very high doses for a long time exibit very weird behaviour and act as if they are not with it long after use has stopped.


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## Claymore (Jun 13, 2009)

york said:


> I think you got it from panicking... For some flower* up reason it doesn't take much anxiety for it to be triggered and stick with you. You've already experienced the symptoms becoming less severe at one point, right?


Yeah I have experienced it but I can't remember what it felt like because im so deep in it now.  Its like it erases all the good memories of feeling pretty good for some stupid reason. I guess its the dissconnection from yourself. And im pretty sure that I got it from panicking also. :?


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## Claymore (Jun 13, 2009)

comfortably numb said:


> Ive seen some people who have used DXM at very high doses for a long time exibit very weird behaviour and act as if they are not with it long after use has stopped.


This is exactly how my cousin is. He looks very pale and acts like he's "out there" but he says he feels normal. And he'll drink 20 to 25 oz of Robotussin DM every night. He prefers the syrup over the Coricedins for some reason. :| Im really suprised that stuff hasn't killed his kydneys yet. He's already had VERY bad kydney stones about 5 times. :roll:


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## comfortably numb (Mar 6, 2006)

I will say this once so everyone get's it. DO NOT TAKE CORICIDIN OR ANY OTHER PRODUCT THAT CONTAINS ANYTHING ELSE BESIDES DXM FOR THE PURPOSE OF GETTING HIGH. This is not only very goddamn dangerous but it is stupid as well since DXM only products are right next to coricidin and everything else and are usually cheaper. As in dangerous im not talking brain damage or organ damage though taking some DXM product that contains chlorpheniramine maleate (a anti-histamine), diphenhydramine (also a anti-histamine), acetaminophen/paracetamol (a non narcotic painkiller that wrecks your liver in high doses), pseudoephedrine (a decongestant that causes hypertension that can lead to heart attacks or strokes in high doses) and numerous other drugs would certainly wreck both your brain and body. Sometimes all in one dose.

If you want to take DXM in pill form for recreational use get robotussin gell caps that have ONLY dextromethorphan as the active ingrediant in them. They are very easy to take. Syrups won't cause much in the way of problems unless you are taking them alot without drinking enough water. But over time all the sugar and other crap in the syrups is not good for you and no doubt will mess up your kidneys a little bit atleast.


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## Claymore (Jun 13, 2009)

comfortably numb said:


> I will say this once so everyone get's it. DO NOT TAKE CORICIDIN OR ANY OTHER PRODUCT THAT CONTAINS ANYTHING ELSE BESIDES DXM FOR THE PURPOSE OF GETTING HIGH. This is not only very goddamn dangerous but it is stupid as well since DXM only products are right next to coricidin and everything else and are usually cheaper. As in dangerous im not talking brain damage or organ damage though taking some DXM product that contains chlorpheniramine maleate (a anti-histamine), diphenhydramine (also a anti-histamine), acetaminophen/paracetamol (a non narcotic painkiller that wrecks your liver in high doses), pseudoephedrine (a decongestant that causes hypertension that can lead to heart attacks or strokes in high doses) and numerous other drugs would certainly wreck both your brain and body. Sometimes all in one dose.
> 
> If you want to take DXM in pill form for recreational use get robotussin gell caps that have ONLY dextromethorphan as the active ingrediant in them. They are very easy to take. Syrups won't cause much in the way of problems unless you are taking them alot without drinking enough water. But over time all the sugar and other crap in the syrups is not good for you and no doubt will mess up your kidneys a little bit atleast.


I dought anyone with DP that has any sense left will do DXM in any form. And if they do, they shoudnt complain about their DP getting worse.


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## comfortably numb (Mar 6, 2006)

Claymore said:


> I dought anyone with DP that has any sense left will do DXM in any form. And if they do, they shoudnt complain about their DP getting worse.


 Yes i would recomend anyone who has depersonalization or derealization to stay away from DXM (unless you take it in low doses used as a cough suppressant but it is near useless for this purpose so it's hardly worth it) or any other dissociative. Atleast if your dp/dr is active anyway but even in remission you take a risk. This excludes dissociative anesthetics used for medical purposes such as nitrous oxide or ketamine used during certain procedures of course.

Basically all i was saying in that post was that if you do go ahead and try DXM to get high make sure the only active ingrediant in the product is dextromethorphan. Anything else and you risk alot more then making your dp/dr worse. You run the risk of death while having a awful trip when you either OD, have something go wrong with your heart or have a stroke. Or even worse you die a slow agonizing death due to acetaminophen/paracetamol poisoning. That would have to be one of the worst most painful ways to die.


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## Claymore (Jun 13, 2009)

comfortably numb said:


> Claymore said:
> 
> 
> > I dought anyone with DP that has any sense left will do DXM in any form. And if they do, they shoudnt complain about their DP getting worse.
> ...


Couldn't agree with you anymore.


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## rob35235 (Feb 21, 2009)

Sorry I disappeared for a few days. My thoughts are scattered and brief today, so I will just ask a quick question Did anyone ever think of a way to agonize the NMDA's without having a neurotoxic effect? Glutamate supplements?


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## Absentis (Jul 10, 2007)

rob35235, you would do well to spend the time to read the entire thread. Your quick question doesn't have a quick answer.


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## odisa (Sep 2, 2013)

So just digging this thread up.. I've a Nefiracetam sample, which among other actions potentiates the NMDAR's (which is different from direct agonism). Going to be trying this out soon-ish, so I'll post back with my experience.

This topic seemed to end up condemning NMDA antagonists (I won't argue with that), however did anyone actually try an NMDA agonist in the end?


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## 35467 (Dec 31, 2010)

I have tried 90.g of l-glycine in a water solution back in 2003 once a day for 6.weeks with no effect. l-glycine is a partiel agonist at the NMDA receptor site. D-serine and d-cycloserine is also partial agonists. D-serine the most potent. Ketamine that blocks the NMDA receptor is recently also found to be a kappa opiopate receptor agonist and ketamines DPD effect comes from the kappa receptor. Full agonist a the NMDA receptor is dangerous and will damage the receptor - good look!


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## Kuldar (Oct 31, 2017)

Hmm.. last post October 2013. What happened to the thread?
Here's a list of supplements I am interested in:

Agmatine
L- aspartate
Quinolinate
Homocysterate
D-serine
ACPL
L-alanine

Can anyone comment on these?


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## willbarwa (Aug 26, 2017)

Judging by all the material and research provided, I would find it interesting if the anesthesia I was given could have made my DP/DR worse. I have no idea what was in it and I remember that before the GA, they gave me some type of sedative (maybe it was placebo).

I'll definitely be more aware of what I put into my body in future cases ESPECIALLY ANYTHING that comes from any hospital/institution.etc


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