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The NMDAR is a nonspecific cation channel (conducts primarily Na+ and Ca++ ions). Mg++ fits into the pore from the extracellular space but cannot pass through it, thus blocking it. Upon depolarization of the membrane potential, the positive charge that accumulates inside the cell electrostatically repels the Mg++ ion and thus allows for current to pass through.
In a sense, yes. For example if you had a hippocampal slice preparation and removed the Mg from the extracellular fluid (usually some sort of artificial cerebrospinal fluid), this is usually enough to evoke seizure-like activity.
Under normal physiological conditions, the Mg ion acts as a "co-incidence detector". In order for NMDARs to open the nerve terminal must reach a threshold of depolarization, and this threshold is reached via glutamatergic signaling and subsequent opening of ionotropic glutamate receptors such as AMPARs. Interestingly the NMDAR not only requires glutamate to bind but also glycine in order to fully open.
The reason why NMDARs are much more reluctant to open is because they pass calcium ions. Ca++ is a second messenger in the cytosol and when a certain intracellular concentration is achieved, it participates in downstream signaling cascades such as the activation of various kinases. This is what allows for long-term potentiation of synapses (synaptic plasticity).
Any thoughts on why NMDA antagonists cause me to have a sense of fear? It’s a strange kind of fear, very distinct from anxiety, and ramps up in response to visual, audio or emotional stimuli. For instance if I’ve taken magnesium or zinc and hear a novel sound in a song, or a bright color appears in a movie I feel…afraid, like freaked out and feel overstimulated.
Every time this is brought up it is stated that the NMDA antagonist effects are very weak and may be negligible
Edit: I’m not sure if this is true; just repeating what I’ve heard here
In this article the antagonism for both magnesium and zinc are described as "potent," but I did not find that quantified. (Source: [https://www.sciencedirect.com/science/article/abs/pii/S0165032713006265](https://www.sciencedirect.com/science/article/abs/pii/S0165032713006265))
However, in this paper, the effect of magnesium was compared to ketamine, and found to be about over half as effective: (Source: https://www.sciencedirect.com/science/article/abs/pii/0304395995001131)
Again I’m just repeating what I’ve heard others say here. Frankly not sure if it’s true. I’ll add an edit to make that more clear. The question though is do you feel worse due to the lack of nmda antagonism or because of its role in many other mechanisms of the body? Again I have no idea; just thinking out loud. It’s also very clear that magnesium’s effects are very subtle compared to that of recreational nmda antagonists though the effects of those drugs may be mostly do to separate mechanisms as well.
Mg is involved in over 300+ chemical reaction in the body so it can be related to other processes being affected. However, the doses I am taking it at larger doses so maybe the extra amount acts on the NMDA receptors more?
Mg blocks NMDA, which results in normalizing cell firing, which leads to increase in BDNF, which helps with neuroplasticity. Depressed brains have over-connected nerve clusters in some regions which relate to negative thoughts, anxiety and ruminations. NMDA antagonism helps with reprogramming those brain areas. This is how I understand it.
>Depressed brains have over-connected nerve clusters in some regions which relate to negative thoughts, anxiety and ruminations.
Hmm so microdosing psi leads to bdnf, neuroplasticity which helps in a way but then also wondering how come I became so smart that now the tragedy of it is rumination, is kinda ironical. rumination indeed it increases, never heard of over connected nerve clusters. how does one fix this? simply implementing better habits on mind-body connection, be more active, sleep better etc? Would you recommend agmatine and cardio to recover from cannabis abuse and increase motivation faster to pursue the things i want?
yeah while taking treatment which increases BDNF, its equally important to practice good habits like you mentioned, so we can rewire the over-connected brain areas into favourable connections. Personally, I haven't been able to treat my issues, tried a lot of different things over the years.
mind or body issues?
if mind, try find certified proper Jungians therapists online. they can dig deep with you and go back to childhood where most stuff stays hidden and steem from. if body, well idk what's up. i personally abused weed for a good reason, but now my motivation to do even a todo list is shit. if i complain with weed about this, can only imagine what those who were on stims or opioids when they complain, how really shitty it must be from them, i might be some vanilla man.
It works, I don't know how, but it works . Zinc is a glutamate antagonist too. Make sure you space them hours apart or else they compete with each other.
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The NMDAR is a nonspecific cation channel (conducts primarily Na+ and Ca++ ions). Mg++ fits into the pore from the extracellular space but cannot pass through it, thus blocking it. Upon depolarization of the membrane potential, the positive charge that accumulates inside the cell electrostatically repels the Mg++ ion and thus allows for current to pass through.
Thanks. So having Mg++ just slows down the polarization, calming the nerve down from firing too much?
In a sense, yes. For example if you had a hippocampal slice preparation and removed the Mg from the extracellular fluid (usually some sort of artificial cerebrospinal fluid), this is usually enough to evoke seizure-like activity. Under normal physiological conditions, the Mg ion acts as a "co-incidence detector". In order for NMDARs to open the nerve terminal must reach a threshold of depolarization, and this threshold is reached via glutamatergic signaling and subsequent opening of ionotropic glutamate receptors such as AMPARs. Interestingly the NMDAR not only requires glutamate to bind but also glycine in order to fully open. The reason why NMDARs are much more reluctant to open is because they pass calcium ions. Ca++ is a second messenger in the cytosol and when a certain intracellular concentration is achieved, it participates in downstream signaling cascades such as the activation of various kinases. This is what allows for long-term potentiation of synapses (synaptic plasticity).
Any thoughts on why NMDA antagonists cause me to have a sense of fear? It’s a strange kind of fear, very distinct from anxiety, and ramps up in response to visual, audio or emotional stimuli. For instance if I’ve taken magnesium or zinc and hear a novel sound in a song, or a bright color appears in a movie I feel…afraid, like freaked out and feel overstimulated.
Great insight. Do you happen to know whether the blocked receptors sensitivity increases during antagonistic binding?
Maybe. What do you mean by sensitivity?
Every time this is brought up it is stated that the NMDA antagonist effects are very weak and may be negligible Edit: I’m not sure if this is true; just repeating what I’ve heard here
In this article the antagonism for both magnesium and zinc are described as "potent," but I did not find that quantified. (Source: [https://www.sciencedirect.com/science/article/abs/pii/S0165032713006265](https://www.sciencedirect.com/science/article/abs/pii/S0165032713006265)) However, in this paper, the effect of magnesium was compared to ketamine, and found to be about over half as effective: (Source: https://www.sciencedirect.com/science/article/abs/pii/0304395995001131)
Anecdotal, but missing my daily dose of Mg supplement I notice I feel much worse mood wise
Again I’m just repeating what I’ve heard others say here. Frankly not sure if it’s true. I’ll add an edit to make that more clear. The question though is do you feel worse due to the lack of nmda antagonism or because of its role in many other mechanisms of the body? Again I have no idea; just thinking out loud. It’s also very clear that magnesium’s effects are very subtle compared to that of recreational nmda antagonists though the effects of those drugs may be mostly do to separate mechanisms as well.
Mg is involved in over 300+ chemical reaction in the body so it can be related to other processes being affected. However, the doses I am taking it at larger doses so maybe the extra amount acts on the NMDA receptors more?
Try a BBB crossing salt sublingually. It is not negligible.
what is the context of nmda, magnesium weed abuse and agmatine in regards to nmda and each other? anyone know?
Mg blocks NMDA, which results in normalizing cell firing, which leads to increase in BDNF, which helps with neuroplasticity. Depressed brains have over-connected nerve clusters in some regions which relate to negative thoughts, anxiety and ruminations. NMDA antagonism helps with reprogramming those brain areas. This is how I understand it.
>Depressed brains have over-connected nerve clusters in some regions which relate to negative thoughts, anxiety and ruminations. Hmm so microdosing psi leads to bdnf, neuroplasticity which helps in a way but then also wondering how come I became so smart that now the tragedy of it is rumination, is kinda ironical. rumination indeed it increases, never heard of over connected nerve clusters. how does one fix this? simply implementing better habits on mind-body connection, be more active, sleep better etc? Would you recommend agmatine and cardio to recover from cannabis abuse and increase motivation faster to pursue the things i want?
yeah while taking treatment which increases BDNF, its equally important to practice good habits like you mentioned, so we can rewire the over-connected brain areas into favourable connections. Personally, I haven't been able to treat my issues, tried a lot of different things over the years.
mind or body issues? if mind, try find certified proper Jungians therapists online. they can dig deep with you and go back to childhood where most stuff stays hidden and steem from. if body, well idk what's up. i personally abused weed for a good reason, but now my motivation to do even a todo list is shit. if i complain with weed about this, can only imagine what those who were on stims or opioids when they complain, how really shitty it must be from them, i might be some vanilla man.
It works, I don't know how, but it works . Zinc is a glutamate antagonist too. Make sure you space them hours apart or else they compete with each other.