# Has anyone here tried taking NMDA agonists?



## Infrared (Nov 27, 2012)

If NMDA antagonists like ketamine, DXM, nitrous and PCP cause dissociation, who's to say NMDA agonists wouldn't do the opposite?


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## Guest (Dec 9, 2012)

that was my idea. you stole it. lol.


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## jaffah (May 13, 2012)

Lamictal is a nmda agonist


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## Guest (Dec 14, 2012)

^^Sorry Jaffah, *Lamotrigine (Lamictal) is not a NMDA agonist.* In fact it is a Sodium Ion Channel inhibitor. It should reduce the excitatory processes of the nerve circuit some [Na does have a higher inherent conductivity than say K] , and reduces the concentration/production of glutamate, as Lamictal does effect things significantly on the pre-synaptic level.


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## jaffah (May 13, 2012)

Lamictal reduces glutamate it is the opposite effect of ketamine


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## jaffah (May 13, 2012)

And ketamine is too agonist of kappa receptor like salvia


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## Guest (Dec 23, 2012)

You'd be smart to stay away from any of those dissociative drugs.


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## Guest (Dec 25, 2012)

Yeah you're right Jonas Salk and Alexander Fleming were hacks.
Their medicine was garbage.


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## noname (Sep 23, 2008)

- "Lamictal reduces glutamate it is the opposite effect of ketamine" >> false, ketamine is a NMDA antagonist

- Ketamine act as kappa opoid agonist >> false, only NMDA antagonist

- would NMDA agonist be a cure for DP : idk but NMDA agonist is potentially strongly neurotoxic (too much glutamate release = excitotoxicity)

- "You'd be smart to stay away from any of those dissociative drugs." >> false for me, these class of drugs (NMDA antagonist : K, Nitrous, MXE...) is actually the ONLY ONE I never experienced dp/dr episode from

(my experience is limited to cannabis, salvia, MXE, N2O or some serotonergic drugs like LSD, 3MMC.

MXE and Nitrous, even if high or repeated dose, never have done bad stuff to me at this moment, contrary to all other (especially salvia)).


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## odisa (Sep 2, 2013)

I'll be trying Sarcosine a.s.a.p. and let you guys know how it goes. This was meant more as a bump though 
Nefiracetam hasn't done much for me, but may in other individuals. Perhaps a longer trial is warranted as well, plus I had my share of confounding variables.


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## AlmostEasy (Oct 21, 2013)

I have been trying Sarcosine for about a month and it's done nothing for me. Sarcosine is a big helper to those with "Negative" Schizophrenia symptoms


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## odisa (Sep 2, 2013)

Ahh that's a pity AlmostEasy. Have you tried NAC?
I was thinking that if Sarcosine doesn't work initially, I might combine with Glycine.
If that doesn't work, I might add Nefiracetam (and possibly NAC as well), though that might be a little overkill.
What dose are you taking?

EDIT: I also ordered Pregnenolone, which I may add if previous are insufficient. Chances are it might cause for more anxiety, conversely it may also reduce it, but I'm up for the risk.


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## AlmostEasy (Oct 21, 2013)

odisa said:


> Ahh that's a pity AlmostEasy. Have you tried NAC?
> I was thinking that if Sarcosine doesn't work initially, I might combine with Glycine.
> If that doesn't work, I might add Nefiracetam (and possibly NAC as well), though that might be a little overkill.
> What dose are you taking?
> ...


Yup, took it with NAC.

In order for Glycine to work doesn't it require like ridiculous amounts of it? I'm not 100% but I thought it was glycine.

And yeah I'm also going to eventually try out Pregnenolone if my Minocycline doesn't work, pretty excited about trying that. Also very prepared for disappointment, it happens a lot with this trial and error nonsense!


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## odisa (Sep 2, 2013)

Yes correct; I just ate 57.6 grams of glycine. It's sweet stuff, and bouncy too. Bit odd on the stomach perhaps.
I've read Minocycline can induce DP, so how is that supposed to work?


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## noname (Sep 23, 2008)

intuition :

I'm really not sure that dp/dr is related to NMDA channels.

some thought/fact, limited by my knowledge :

- if dp/dr is related to NMDA and if dp/dr come from a process like excitotoxicity, there is nothing to do. "Agonising" NMDA receptor is just risking fragilising more neurons.

- If dp/dr is related to NMDA channels outside excitotoxicity, we would have far more case of ketamine/nitrous/MXE/DXM induced DP/DR.

- MXE and DXM is less used than Ketamine and we have interestingly more report of DP/DR/HPPD from these two first one : what distinguish MXE/DXM from ketamine/nitrous is serotonergic activity. DP/DR ketamine induced is a fucking rare occurence, compared to the frequency of usage.
MXE/DXM dp/dr/HPPD should perhaps be linked to classical HPPD lsd induced (5ht activity).

- I can get backed 24/7 for a month on MXE and not getting dp/dr. 1 time with 1/2 dose salvia divinorum = 4 month dp, and this drug have nothing to do with NMDA to our current knowledge. 2 week on cannabis and dp for 4 month too.

It's a really complex subject due to probable interaction beetween many type of receptor (and the fact I understand nothing about these stuff), but NMDA alone seem imo not linked to DP/DR... Or we would have far more report of dp/dr-like problem with NMDA agonist/antagonist.

NMDA antagonist is even the ONLY substance wich seem to be relatively safe when it come to DP (same risk as alcohol, opiate... no 0%, but low). Read a forum about drugs, go in the extasy part, the cannabis part or LSD part, you will get a shitton post about permanent dp. In the dissociative part, aside DXM wich is a special case (many serotonergic activity), you will find... close to 0 case.

Conclusion : next time, do ketamine.

PS : if anyone can explain the brainfuck stuff - lamictal reduce NMDA activity and block ketamine dissociative effect, ketamine reduce NMDA activity and make you dissociated. I never understanded that. It's perhaps about pre or post synaptic stuff, another stuff that I never got clear.


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## noname (Sep 23, 2008)

I forgot the main point of my post :

If any of you is a dissociative connoisseur (I speak only about NMDA antagonist, not opoid kappa), you can't say the dissociation effect from dissociative = dp/dr.

There is similarity (as dissociation from kappa agonist can lead to a kinda similar irreality impression than NMDA antagonist visualy speaking), but it's NOT dp/dr.

I can't say it a better way, it's the first thing wich have come to myself when I firstly tried NMDA antagonist.

Dissociation from cannabis, for example, is closer to dp, and dissociation from low dose kappa agonist is closer to DR.

idk

it's hard to say

but it's not the same thing, that's all


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## odisa (Sep 2, 2013)

noname:
Agonizing the NMDA receptors needn't always result in excitotoxicity. It is only when it passes a threshold I believe. And there are many substances that limit or prevent excitotoxicity which one could use in conjunction with a NMDA (co)agonist.



> - If dp/dr is related to NMDA channels outside excitotoxicity, we would have far more case of ketamine/nitrous/MXE/DXM induced DP/DR.


Perhaps.. Though one person can smoke a big fatty and laugh his ass off, whilst another can smoke 1 puff and have a panic attack. Thus this needn't mean that there would be more cases of DP/DR induced by the aforementioned substances.

If it is serotonergically mediated as you propose, then there are few options left.. SSRI's are shit which we all know. Tianeptine may be an interesting avenue for DP treatment, should that be the case. I've tried it but to no avail though.

Indeed the endo- opioid and cannabinoid systems may well be implicated in the sustenance of DP. Personally I believe KOR antagonists are a more promising avenue than NMDA agonism, but being the matter that acquiring a KOR antagonist would require relatively large sums of money, a reliable custom synthesis lab, and proper communication skills, this is something I don't see happening soon. Plus you'd want to have a 3rd party analysis to confirm quality/purity. The only way that's conceivable to achieve this would be to organize a group buy of said substance, and from what I've seen there are very little people here interested in such endeavors. IF we can get enough people interested, and the forum allows it, then yes I can see this happening.

As for the cannabinoid dysregulation theory: perhaps CBD would be of merit to those with DP; however I've tried this myself and it didn't exactly help DP. It was great for anxiolysis, as well as sleep, and improved overall general wellbeing slightly, but for the current price it is sold at this is also not a realistic option. Though of course I'd like to see more people try this and report their experiences with it.

As for the low occurrence of NMDA antagonist induced DP.. If I'm not mistaken there are reports of this. The thing with drug-induced DP/DR is that not everybody gets it, or at least not the chronic form. Anyway; I think you've also failed to mention PCP/Angel Dust, which is a NMDA antagonist and does induce DP.

I propose a poll to screen for the most common substances inducing DP, combined with frequency of use, time DP'd, etc. to get a better view about this.

About the Lamotrigine/Ketamine study.. Haven't read it myself, but Lamotrigine reduces Glutamate via natrium+calcium channel inhibition (iirc), and Ketamine antagonizes the NMDA receptors. There's a difference. Other than that I'm not sure.

Meanwhile in the batcave, I've ditched Glycine as it was making me very nauseous. Tried Pregnenolone (5mg) yesterday and I felt very "off", however this could've been endogenous weirdness, thus it's not exclusively attributable to my use of Pregnenolone.

Still don't have my Sarcosine in the mail 

Other NMDA agonists are D-Aspartic Acid and D-serine, if anyone is willing to give those a shot (I'm saving my money for other approaches). D-AA I believe is a full agonist (comparable to NMDA itself in potency), as opposed to Glycine, D-Serine and Sarcosine, which are co/partial agonists. This may be more effective: Sarcosine+Glycine+D-serine+D-AA. Then you will have sufficient Glycine available, of which the reuptake is inhibited by Sarcosine, the D-serine acting as a more potent glycine binding site agonist than both Sarcosine and Glycine, and the D-AA agonizing the Glutamate/NMDA site of the NMDA receptor. Then to perfect it, one may add excitotoxic preventing agents (idk, e.g. Coluracetam?) as well as a methyl donor (not sure which of the dynamics of D-AA to NMDA, but let's just say Methylcobalamin or whatever to make it sound nice).

So there you have it: NMDA soup. Volunteers, anyone?


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## AlmostEasy (Oct 21, 2013)

Having success with Minocycline, not ready for the full report since it's only been 3 days but I feel like this is it for me. I may have finally found something that can free me from the most hellish existence I could ever imagine a person could experience.

I'd do some research on it odisa, it looks you're using common treatments for negative schizophrenia symptoms which I tried as well and had no results. I tried Sarcosine + D-AA for several weeks with zero effect. Within minutes I felt changes with minocycline.

I promise to do a full report once I fully figure out if this is the one, I'm trying to take it slow as there have been some intense moments in the transition period and I'm in no rush to push it too fast, I'm on 50 mg/day compared to the trial dose of 200 mg/day.

Again I'm treating negative schizophrenia symptoms, which can overlap quite readily with DP/DR symptoms and in my opinion are what a lot of people on here are suffering from but are terrified to admit. Google the "PANSS" test and see if you relate strongly to the negative symptoms, and if you do this may be something incredibly important for you.

Be careful with how you diagnose yourself though as I have seen several reports of this causing some large problems with people as well, which is strange because in all of the clinical trials for treatment of negative schizophrenia with minocycline there was staggering success. I dunno man it's tricky to say who should take it/try it, but if you tried to take mine away from me, you just might get knocked out.


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## Nathanael.A. (Apr 16, 2013)

The jury is still out on the neurochemical mechanisms behind with the development of DPD, and when you start thinking about specific receptors, its gets stupidly tricky because there are many different types of receptor for each neurotransmitter which each create slightly or greatly differing effects, not to forget there are a myriad of sub-types of each of those different receptors, and any sort of activation of any combination of these receptors influences other neurochemical systems and has many downstream effects.

The sprinkling of evidence which has been done on DPD and some firsthand reports from psych's themselves hinted to me that basicly the idea is that somehow 'glutamate' initiates a suppression of emotion in DPD.

Baring in mind the lack of information, the different neurochemical mechanisms behind dissociation caused by the ingestion of exogenous dissociative agents such as Ketamine, MXE etc, although feeling somewhat similar, is probably completely different to the neurochemical mechanisms behind the endogenous, organic dissociation which occurs in DPD.

Basically, at the moment we known this: Ketamine causes dissociation, apparently by NMDA antagonism, but concurrently this results in a massive increase in bioavailable glutamate due to the blocking of such receptors that then stimulates all the other kinds of glutamate receptor (AMPA, Kainate etc), but the role which this has in the subjective effects of ketamine is unclear. Research has shown however that lamotrogine reduces glutamate release and synthesis on a whole, and this is thought to be behind its proven therapeutic effects in DPD.

From this we can infer that glutamergic neurotransmission somehow mediates DPD, so that altho dissociation caused by ketamine is though to be down to NMDA antagonism, it might also be due to the potentiation of glutamate at other receptors. Following this rationale and the therapeutic effects seen with lamotrigine, we could assume that administration of any agent which potentiates glutamate neurotransmission of any kind could worsen DPD, such as taking agents such as Sarcosine, Piracetam, Nefiracetam etc

So obviously if ur having difficulties with DP/DR, its not a good idea to go sniff some ket or MXE,but niether is it a good idea to go take a drug which boosts glutamate levels or neurotransmission indirectly such as sarcosine/ Racetam's

Regards'


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## odisa (Sep 2, 2013)

Following that theory, then a potentially good target would be a Glutamate Decarboxylase Enhancer.. you know, if it exists at all.


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## AndyD (Nov 24, 2011)

I believe Depakote increases GAD65 levels. Valerian may also but they aren't sure and I'm not either. I tried Minocycline a few times and I did feel a little like the "old me" initially. I felt more connected and also felt my brain was protected (probably from excitotoxicity) but after a while I ended up feeling more DP and a lot of "intracranial pressure" so had to stop.

Anway, this gets my vote as one of the best topic on this entire forum... I think excitotoxicty and overactive glutmate receptors play a major role in DP.... I'm sure most people are already aware of this so, but still more discussion would be interesting, especially regarding meds that influence the glutamate and NMDA receptors


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## luctor et emergo (May 22, 2015)

Aside from being a KOR antagonist, what else is currently known about ALKS-5461? 
Maybe something for a new topic?

Lets hope that our excitement will be justified.


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## 2141zach (Sep 14, 2015)

DXM induced the dp I have for 3-4 months now I took a high does though are you talking microdoses? I havnt had much trouble with weed except the high felt different like I wasnt high but then got better the second time I smoked but I havnt smoked since, thinking of trying again?


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