Comment · Fri, October 30, 2020 · Natrium Health & Nootropics Depot
How fast does Agmatine Sulfate reduce tolerance?
What they were answering
PhantomZero77 · 3 points
The reason I’m asking is because there have been numerous anecdotal reports about using agmatine to successfully reduce phenibut tolerance. You can find loads of them on r/quittingphenibut for instance. A lot of people also use it to supposedly reduce or at least prevent tolerance to kratom as well.
Apparently this is due to agmatine’s affects on Glutamate NMDAr receptors.
https://en.m.wikipedia.org/wiki/Agmatine
Agmatine also regulates the GABA/Glutamate balance, further giving evidence to claims that it has a role in reducing phenibut tolerance.
https://link.springer.com/article/10.1007/s00210-020-01910-5
Agmatine also affects Voltage gated-Ca2 channels which Phenibut also hits on.
https://pubmed.ncbi.nlm.nih.gov/15000878/
Further, agmatine has affects on neurotransmitter receptors serotonin 5-HT2a and 5HT-3, which are some of the brains "feel good" chems, and this can also explain why a lot of people report reductions in their depression from supplementing it.
https://pubmed.ncbi.nlm.nih.gov/15857629/
u/MisterYouAreSoDumb, I’m curious as to what your thoughts on this are.
u/MisterYouAreSoDumb · Natrium Health & Nootropics Depot
Tolerance is a very complex thing. However, we do have a lot of anecdotes about NMDA antagonists helping with many things. It's because the NMDA receptors are linked to many other receptor systems in the body, and they control a lot of signaling cascades. So while agmatine doesn't have direct effects on the GABAb receptors, it can still affect them by blocking the NMDA receptors. You are also correct in saying it affects more than just NMDA. So it could be a combination of things that is leading to the beneficial effects from agmatine.