Understanding Excitotoxicity

[Lightning-Nl]

In excitotoxicity, imagine the neurons in your brain as little engines. They keep getting faster and faster and combusting, as more Gasoline, but in the case of your neurons, ions that excite and change the charge of your brain. To the point that it will explode with more gasoline input, or ion stimulation through molecular release of excitatory transmitters that let in more of a positive charge.

As you charge the neuron more and more it will eventually explode due to overcharge or over stimulation or too much input of a combustible material.

So, when the neuron has too much gasoline let in, it will explode because it gets faster and faster until there is too much stimulation by excitatory neurotransmitters such as Dopamine, Norepinephrine, Acetylcholine, Glutamate, and Serotonin. That overcharge your brain too much.

You can also think of it in terms of circuitry (or a bolt of lightning). Where a bolt of lightning hits a powerline, and charges it too quickly to the point of exploding.

In terms of circuitry. You charge any component too much over its voltage rating, and it will explode due to overcharge.

 

[allone]

i got acamprosate (Campral) prescribed for this specifically. not sure if it does anything really. it says take 3 to 6 pills a day. and it has low availability wtf. really, is this the best people can get for excitototoxity? but hey, it has a very long history of use, so it must be doing something, i think....

 

[Xorkoth]

Had to look it up... acamprosate is prescribed for alcohol dependence treatment. It appears to work as a positive allosteric modulator at GABA-A and inhibits NMDA to some extent, which reduces excitotoxicity resulting from alcohol withdrawal, since it prevents some of the overactivation of these systems. I don't think it would prevent excitotoxicity in a generic way, but 0nly if your GABA/NMDA systems are out of whack as a result of abuse of drugs that activate those systems.

 

[allone]

i dont think it prevents or does anything of substantial value really. bunch of pharma garbage.

anyone who adds some ACTUAL WORKING SUBSTANCES against excitotoxicity, i will thank you with whatever rewards i can afford to give!

 

[Xorkoth]

The wiki suggests it is only marginally effective against alcohol dependence. it is supposed to reduce withdrawals and when combined with other forms of treatment, help curb cravings. So it doesn't sound all that effective but instead is an adjunct to therapy and treatment. Nothing I read suggests one should expect it to magically prevent excitotoxicity in a general way, but as a weak positive allosteric modulator for GABA-A and weak antagonist of NMDA, it should somewhat help reduce withdrawal severity and somewhat satisfy physical need and craving for alcohol (or benzodiazepines).

 

[plumbus-nine]

i got acamprosate (Campral) prescribed for this specifically. not sure if it does anything really. it says take 3 to 6 pills a day. and it has low availability wtf. really, is this the best people can get for excitototoxity? but hey, it has a very long history of use, so it must be doing something, i think....

I had some acamprosate and took 3 times the recommended dosage (6-9 pills at once) and felt absolutely zero. Worthless. Memantine is the real deal but there's much space left for inventions. Just now being on 50mg memantine (20mg/d is the recommended dosage but it builds up so this dosage compensates for that) and feel awesome despite opioid withdrawal. If it works against excitotoxicity from other origin, I dunno but I guess it's pretty generic by blocking excess glutamate. They say it prefers NMDAr's which are over-activated but remains natural activity yet it behaves like any dissociative just a weak one. If dosed high enough you get the full experience.

Don't get why doctors don't prescribe it more often. DXM is another one which has potential but also some potential toxicity. I don't tolerate it anymore.

Agree to @SwampFox56 description of excitotoxicity, it's similar to my own imagination

 

[allone]

i would prefer recommendations, like something more accessible than memantine for excitotoxicity.
besides ive tried memantine before which i thought was OK, nothing amazing and then i mixed it with suboxone and i had a hell of a trip. not sure but i would be careful mixing memantine with some strong meds, including things like suboxone or antidepressants.

 

[plumbus-nine]

i would prefer recommendations, like something more accessible than memantine for excitotoxicity.
besides ive tried memantine before which i thought was OK, nothing amazing and then i mixed it with suboxone and i had a hell of a trip. not sure but i would be careful mixing memantine with some strong meds, including things like suboxone or antidepressants.

I mixed memantine with morphine and got just the effects I know from memantine alone. Weird. My body seems to be pretty efficient in metabolising stuff. I take 160mg propranolol to keep my tachycardia in check and my gf took 40mg and felt it being overwhelming..

 

[AlphaMethylPhenyl]

Here I'm gonna say real quick that meditation has helped me calm down like nothing else, and given the proven positive effects on the brain, almost certainly works against excitotoxicity. Other than that, work on stress levels. Gah, I know this isn't MH. I'm a religious MH agent.

Labeling nt's as excitatory or inhibitory, I must say, isn't really the best method of understanding the brain. It's more about the receptors that they affect. Just thinking, for example, about autoreceptors. Other than that, the monoamines can activate both excitatory and inhibitory receptors.

But yeah, no denying the thermodynamics of electricity on biotic matter.

 

[cdin]

I mixed memantine with morphine and got just the effects I know from memantine alone. Weird. My body seems to be pretty efficient in metabolising stuff. I take 160mg propranolol to keep my tachycardia in check and my gf took 40mg and felt it being overwhelming..

wow 160 of prop is crazy. i take 20 and im getting bradycardia badly be super careful if you already have these excitotoxic problems using NMDA antagonists -- sure they are great for lowering glutamate.. but that's the problem as well. If you take them chronically, you WILL upregulate the glutamate sites. fine for as long as you have NMDA ant activity going, but as soon as you don't the reregulation process is a painful/shaky/very toxic feeling wd situation it takes a long time to do, and the shitty thing is it seems to take a very long time to undo as well.

 

[plumbus-nine]

wow 160 of prop is crazy. i take 20 and im getting bradycardia badly be super careful if you already have these excitotoxic problems using NMDA antagonists -- sure they are great for lowering glutamate.. but that's the problem as well. If you take them chronically, you WILL upregulate the glutamate sites. fine for as long as you have NMDA ant activity going, but as soon as you don't the reregulation process is a painful/shaky/very toxic feeling wd situation it takes a long time to do, and the shitty thing is it seems to take a very long time to undo as well.

Yeah, NMDA receptors don't joke. I had bad rebound from my 3-year disso binge but eventually things did settle. Yet memantine withdrawal (by a quack in psych ward, he said he couldn't continue me on memantine cause off-label and put me on sodium valproate) provided me the first and so far only real manic episode in my life.

You get bradycardia from 20mg propraonolol? Crazy.

 

[cdin]

Yeah, NMDA receptors don't joke. I had bad rebound from my 3-year disso binge but eventually things did settle. Yet memantine withdrawal (by a quack in psych ward, he said he couldn't continue me on memantine cause off-label and put me on sodium valproate) provided me the first and so far only real manic episode in my life.

You get bradycardia from 20mg propraonolol? Crazy.

im also quitting nicotine AND opes atm, plus my HR/BP is naturally low. I was only on it for PTSD reasons, which have been corrected by low dose psilo. so now i dont have the condition it was treating me for, and two things pulling my BP down. im getting full shaking/HR at 160 episodes as my BP bottoms out ( and ya, rebound/WD from constant NMDA is FUCKING CRAZY. I had the distinct displeasure of doing a BZD wd at the same time. sadly, im sure i did a ton of excitotoxic damage i could have avoided if i had known what was going on (come off the NMDAs first, then taper the BZDs instead of both at once)

 

[allone]

nobody can really know or notice excitotoxicity. its very long term subtle detrimental effect. that is unless you are a severe alcoholic. then it can be quite obvious when you stop drinking all of sudden. its the best way to evaluate anything that might mitigate it in such instance, im certain.

 

[plumbus-nine]

nobody can really know or notice excitotoxicity. its very long term subtle detrimental effect. that is unless you are a severe alcoholic. then it can be quite obvious when you stop drinking all of sudden. its the best way to evaluate anything that might mitigate it in such instance, im certain.

Stopping a disso binge would come to similar like stop drinking after being an alcoholic, or is alcohol worse because of additional GABAergic effects?

 

[Xorkoth]

Alcohol is much worse, exactly because of the GABA activity. Overactivity of NMDA is not comfortable or good, but lack of GABA is far more dangerous and damaging. No one in the history of the world has ever been in danger from dissociative withdrawal, to my knowledge. In fact most people don't even consider dissociatives to be physically addictive. GABAergic addiction is very real though, and the most dangerous of any drug dependence. Many people have died from GABAergic withdrawal.

 

[allone]

"GABAergic addiction is very real though, and the most dangerous of any drug dependence. Many people have died from GABAergic withdrawal"

can you please elaborate more on this since there is scarce info out there on this, sadly.

 

[Xorkoth]

What do you mean? There is a shit ton of information everywhere about GABAergic withdrawal being dangerous and potentially deadly. It's talked about on Bluelight all the time over in BDD/OD, and everywhere else on the Internet. Because GABA is the body's main inhibitory neurotransmitter, during withdrawal, you are not getting nearly enough since your receptors have downregulated, and you will experience intense anxiety and paranoia, and if it is severe enough, seizures.

 

[allone]

ive experienced it myself but i thought people can share their personal experience so i can relate. yes im pretty aware of it all over the net and shit, been reading about it many times etc. but if i meet people in the same situation as me, then we can actually discuss and figure out a solution to this gaba wd problem.

 

[acklac7]

What if you coated the over-excited Neurons with some Neuronal KY-Jelly, making them slide smooth-as-silk through the Brain and not become damaged? That would be the ticket, wouldn’t it?

 

[allone]

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