Cannabinoid System

[Limpet_Chicken]

Yeah, I'm not entirely sure the OP has a brain to TURN to palsied, degenerate mush.

If he isn't trolling, then OP-think about it this way: what do the common drugs with anxiolytic (anti-anxiety) properties have in common? they are, overall, inhibitory. Be it GABA agonists, alpha2 adrenergic autoreceptor agonists (decreasing noradrenaline release), antimuscarinics in low doses (way below delirient doses), opioids, and what happens in withdrawal-one gets a highly excitatory overall tone as the blowback from excess, in the guise of W/D symptoms, and a recoil towards excessive excitatory effects.

This is the kind of thing you would (first) induce. Along with seizures, then brain damage from which you would probably not recover much if at all, and which would specifically target your ability to learn, to form memories, to function at all, in destroying the hippocampus.

So first you'd cause yourself a living hell most probably, along with the seizures, then brain damage. And then you'd spend the rest of whatever miserable, tortured scraps of existence living a brand new life.

As a brussel's sprout. Shrunken, atrophied and completely without any value to either self or mankind at large.

If you go ahead now, knowing that, then when you get reincarnated as vegetation and condemned, if you survive, to sitting in a wheelchair drooling and spasming, in a diaper full of your own shit and piss, then when that causes a bedsore and infection sets in and eventually, slowly and unpleasantly, kills you, hopefully at least that will be a small mercy, when you don't have to be alive anymore. Or at least, your body doesn't have to continue functioning. Because there won't be much left of anything else. Just a screaming, suffering tube of meat that gets fed slop from a spoon and shits its diaper.

For the rest. Of. Your. Existence.

If you are this suicidal and self-loathing, try seeking counselling. And if you are going to kill yourself no matter what, even after counselling and therapy, antidepressants etc. then you could at least make it clean, and quick, if you go and suck on a shotgun barrel and operate the trigger with your feet. Your brain matter would end up in a similar state to what would become of it if you take NMDA like a fucking idiot, the primary differences are the smell of cordite, the wider distribution of your remaining brain matter along a wall and the fact that somebody has to clean it up with a shovel and brush, as opposed to dumping the body in a hole in the ground in one pie...as a consecutive unit.

 

[Weltmeister]

OP is probably a troll. He came here to ask questions but ignored all advice. Then he goes on talking about taking excitotoxins to repair his brain.

 

[sekio]

I think the only saving grace is that NMDA is unlikely to pentrate BBB due to its polar nature, so at best nothing will happen.

According to wiki D-aspartate is naturally present so presumably there would be enzymes in the liver that would demethylate NMDA too.

 

[trainman04]

I think the only saving grace is that NMDA is unlikely to pentrate BBB due to its polar nature, so at best nothing will happen.

According to wiki D-aspartate is naturally present so presumably there would be enzymes in the liver that would demethylate NMDA too.

yes D-aspartate is naturally present but not pure NMDA and theres no bacteria or anything for it that destroys it. So basically its synthetic...

if u read the reviews about this supplement which has pure NMDA u can see lots of people notice sleep benefits. which i belive is due to NMDA activation
https://www.bodybuilding.com/store/iforce/intimidate-srt.html

and its the 1 i ordered i think it should be here on friday! cant wait. Memantine worked great for me and its an NMDA partial antogonist.....

 

[trainman04]

just a question will increasing CB1 increase anandamide ??

 

[sekio]

You keep saying "increasing NMDA" or "increasing CB₁"... Do you mean increasing the sensitivity of CB₁ receptors, the number of receptors per cell, the number of receptors total, or increasing the level of activation of CB₁? Because those are all different things. And doing any of them won't increase natural synthesis of anandamide. To increase natural synthesis of anandamide, you should engage in regular aerobic exercise and eat a diet high in polyunsaturated fats. There's no magical receptor that will suddenly boost production of neurotransmitters.

You seem to be missing the forest for the trees so to speak, because at the end of the day the degree of receptor activation is what matters, not the amount of receptors. If your cannabinoid system is not getting stimulated adequately by the natural levels of anandamide, adding more receptors will do nothing because there's only so much anandamide to be released at once, and if the ananadamide doesn't bind, there is no transmission of a signal and the cells won't react. That is to say, having more receptors won't do you any good unless you also have the neurotransmitters to activate it.

Memantine worked great for me and its an NMDA partial antogonist.....

If memantine helped, then taking NMDA will do the opposite... NMDA activates NMDA receptors whereas memantine blocks activity at NMDA receptors. They do the polar opposite of each other.

theres no bacteria or anything for it that destroys it.

Just because a compound is synthetic, doesn't mean that it won't get metabolized and excreted.

 

[Limpet_Chicken]

If memantine worked great, as said, NMDA will do the exact opposite, aside from turning you into plant life able to do nothing but suffer and stew in your own shit-filled diaper until infection finally, mercifully, kills you slowly and unpleasantly, unless the NMDA killed you first. Which is about the best you could hope for.

Memantine is a low-affinity NMDA receptor ANTagonist, with rapid on-off binding kinetics, that works to inhibit overactivated NMDA receptors selectively, due to its binding to the opened channel selectively, and thus selectively inhibiting over-active NMDAr-ergic neurotransmission. If memantine helps, go with it, its not a harmful drug, as opposed to NMDA itself which isn't even a drug, it is a POISON with no medical use whatsoever. And a poison which doesn't just sicken, it KILLS, OR turns the victim into a cabbage, in a particularly torturous way.

And if an NMDA antagonist helps you then memantine is a great idea, why would you want to, knowing what helps already, take something that does the exact opposite. What is the opposite of helping? it is hindering and harming. Which is just what will happen. There isn't even the slightest chance it will be of benefit. If you really must try a proglutamatergic drug, try one of the 'racetams, or LOW doses of an AMPAkine, ideally one of the low-impact types (a lot safer, whilst they produce less robust increases in AMPAr activation compared to high-impact types, the latter are more dangerous in excess and need great care in their dosing), a 'racetam known for AMPAr stimulatory properties would be aniracetam, which if used ought to be taken with a source of fat, such as fish oil capsules, and will not do you harm. Ideally take with lecithin or another choline source. Pramiracetam is probably the best of the common 'racetams, and if dosed low, an example of an available AMPAkine, sunifiram, although AFAIK a high impact type, could be used, at doses of 5mg or less. AMPAr stimulation IIRC increases NMDA receptor activation indirectly, and just as with NMDA receptor stimulating compounds, orthosteric agonists (I.e at the glutamate site) are well known to be permanently damaging (if they don't kill the victim) excitotoxins, the damage from which, as would NMDA agonists, results in seizures, possible death, severe gastrointestinal upset and PERMANENT damage to survivors.

 

[trainman04]

memantine is a partial it blocks some nmda and increases other. becauase I dont think fda would allow a drug that blocks a receptor 100% that can lead to concequenses.
even if nmda is full antagonist. the fact that memantine targets the nmda will disturb the normal rhytme u have going on and will cause an effect. Hence I felt less anxiety. doesent mean blocking was the reason i felt less anxiety its becuase it just hit the receptor.

@sekio according to my snp my cb1 are sensitive but they have less activation and I have less of them. So I wanna increase both the activation AND the amount of cb1 receptors.

But then theres 2 more SNP mutations for my cannabinoid system that confusing me and I dont know what they affect
description( Contains Risk Alleles) https://www.selfdecode.com/gene/crhr1/

desc(Contains Risk Alleles / Potentially bad gene) https://www.selfdecode.com/gene/cnr1/

 

[Limpet_Chicken]

Thats just it with memantine, it DOESN'T produce much blockade at all of regular natural firing of NMDA receptors. Its pretty specific in only blocking excessive (I.e disease-state) overactivity of NMDA receptors.

It functions as an uncompetitive weak antagonist, that binds the open channel, like the magnesium cation does which sits in the ion channel at resting potentials of the glutamatergic neuron, and when the neuron is activated beyond depolarization threshold and transmits an action potential, the Mg++ cation that normally holds the receptor quiescent is spat out, which is when Mg++ binds by blocking the pore again. And coupled with its relatively weak binding and rapid on-off kinetics, that makes for a drug ideal for blocking NMDA receptors in such a way that overactive NMDA receptors are somewhat blocked whilst not inhibiting normal neurological activity to a great degree. One CAN use it as a dissociative, but it takes huge doses compared to pharm doses (100s of milligrams compared to the bottom-end of pharmaceutical dose regimes (lowest dose tablet is, IIRC, 5mg).

And no, it won't make taking NMDA itself safe. Throw it away. Flush it down to the arse-end of north korea, because that is where it belongs)

 

[trainman04]

just so U know limpet chicken . U telling me to get rid of the NMDA just fuels me even more to try it. unfourtnunaly My NMDA didnt arrive today . hopefully on monday.

I think I have PFC problems.
https://www.sciencedirect.com/scienc...66432813002635

When the amygdala is hyperactive, PFC is supposed to inhibit . But due to my cannabinoid receptors CB1 being low and underactivated it doesent happen. If I can activate the NMDA maybe it can stimulate the PFC and calm my amygdala. But all in all I think my Main problem is my endocannabinoid system is all F#cked up.

 

[Moxious]

just so U know limpet chicken . U telling me to get rid of the NMDA just fuels me even more to try it. unfourtnunaly My NMDA didnt arrive today . hopefully on monday.

I don't think you're understanding us at all here man, this isn't like some parent telling their kid not to try dope because it'll fuck them up, i.e. they'll get hooked, this is like saying don't drink bleach, or eat battery acid - these things might not kill you (though they also might!), but they will DEFINITELY not do anything to help you out.

If that makes you want to do this more, then whatever, we tried. You just seem to be looking for people to blindly agree with you, and this is not the place for that.

 

[Limpet_Chicken]

Yes, moxious couldn't have put it better. If you said you had piles, and insisted on taking a red fuming nitric acid enema in order to burn them off, would you still insist on it when told the likes of steroid creams and a doctor appointment would do the job without inflicting harm and a possible agonizing death? No, you probably wouldn't. (although, admittedly I take the example in question from some 17th-century medical books which actually did use HNO3, although presumably not NOx-saturated fuming nitric, as a treatment for piles)

This isn't me proselytizing against drug use...hell I've been here since 2005, and I've taken things and made things a good many people have never even heard of, and I still do. I'm NOT the kind to preach anti-drug messages, but whilst it has uses in CELL CULTURES or isolated patch-clamp recordings, where a portion of cell membrane is used for electrophysiological studies of ion channels, in intact animals (although sadly, this is done) administration of NMDA is sadistic way, way beyond the realms of acceptable treatment of lab animals (personally I am against ALL testing in live animals), but excitotoxins really are brutal and sick, sick shit to subject a living animal to. Its the kind of thing I'd use on a fucking copper if I could get away with it, its that damn nasty.

It is NOT a drug, it is a POISON, pure and simple. Giving it to a human being would be an unforgivable act of brutality, some truly sick-fuck shit.

The effects of NMDA agonists of the glutamate site (there has been development of glycine allosteric site partial agonists for human use, but an orthosteric [orthosteric means binding at the same site as the native ligand, E.g GABA to GABA receptors, glutamate to glutamate receptors, in the case of NMDA receptors, they were never 'intended' to be activated by NMDA, it isn't a bodily neurotransmitter but a synthetic research tool and poison, the reason they were named NMDA receptors is the fact that N-methyl-D-aspartate was the primary discovered highly selective ligand for the receptor, just as how muscarinic acetylcholine receptors were named for their binding muscarine, a fungal neurotoxin, and nicotinic acetylcholine receptors were named for their sensitivity to nicotine and to differentiate the nicotine-sensitive receptors from those which respond to muscarine but which are not activated by nicotine. In both cases neither compound are the native neurotransmitter, which is, in both cases, acetylcholine)

The glycine-site partial agonists (NMDARs require, before the glutamatergic neuron is to fire an action potential, not only to bind glutamate or aspartate, but also, on a separate allosteric binding site, the presence of glycine to bind to the receptor as a co-agonist)

If you really want to try and increase NMDA receptor-based signalling, glycine would be an awful lot safer. NMDA, if it penetrates the blood-brain barrier, WILL do damage, it WILL quite literally fry populations of neurons involved in learning, memory and capacity to think. Fry them to death, and the damage, assuming it does not kill you outright, will be with you for the rest of the pit of abysmal misery and suffering and torture that whatever is left of you is condemned to for the rest of your natural lifespan-assuming you are still able to prepare food and eat it, and don't just starve to death instead.

If it does penetrate the BBB, and sub-acute doses are taken, the damage might not be immediately obvious but will be cumulative, and one way or another you are going to end up as vegetation. The best thing you could do for yourself if you do poison yourself with NMDA, *IF* you are able to, in the condition it will leave you in, would be to kill yourself as quickly and humanely as possible. A shotgun blast to the head with the barrels in your mouth would be a lot kinder than what NMDA would do to you, at least you'd die properly and not be left a piece of meat capable of nothing but to suffer.

 

[sekio]

I think I'm going to close this thread because OP is ignoring all the advice everyone is posting. Since OP is so confident that taking excitotoxins will magically fix anxiety, let them do it.

You just seem to be looking for people to blindly agree with you, and this is not the place for that.

^ This, x100.

memantine is a partial it blocks some nmda and increases other. becauase I dont think fda would allow a drug that blocks a receptor 100% that can lead to concequenses.
[..] doesent mean blocking [NMDA] was the reason i felt less anxiety its becuase it just hit the receptor.

This shows such a wanton lack of understanding of pharmacology ("agonism and antagonism don't matter, all that matters is receptor occupancy") and you seem uninterested in learning anything beyond what you can make up or infer from gene-testing sites.

So good day to you sir.