Comment · Thu, April 18, 2013
Why does psychedelic-induced glutamate release not cause excitotoxicity?
Original post in this thread
AtomikPi · 14 points
It's my understanding that serotonergic psychedelics cause glutamate release. More broadly, there was a very cool fMRI study showing that psychedelics disable certain "filtering" regions of the brain - very much in line with Huxley's argument in The Doors of Perception.
Now obviously it's well-established that psychedelics don't cause degeneration of cognitive abilities. I'm thinking of a study from the early 70s showing no loss of cognitive abilities in individuals who'd used LSD an average of 50 or so times.
So why, from a neurological perspective does the glutamate release not cause excitotoxicity? Is the magnitude not large enough? The brain repairs itself?
Please note I've googled this and not come up with any conclusive result. There is a thread saying "it doesn't" / "not large enough of an effect" but no actual explanation or substantiation of that claim.
What they were answering
Cannibalsnail · 8 points
I haven't got time to look into it right now, but could NMDA be the missing factor here. NMDA antagonists block glutamate neurotoxicity. 5HT2A agonists block NMDA antagonist neurotoxicity. Both are linked to D2 upregulation etc. It's clear the 2 systems are associated somehow. Whether this is important, or even relevant I have no idea, just throwing ideas around.
If you can be bothered to read this it might be relevant.
http://www.acsu.buffalo.edu/~zhenyan/5HT+NMDA-firing-MCN.pdf
u/MisterYouAreSoDumb
Yeah, it has to be an NMDA modulation effect from the agonism of the 5-HT2A receptor. Given that they block NMDA antagonism neurotoxicity, that mechanism must work both ways.
http://voxoz.com/publications/cat/Systems/Biological/Neurochemistry/5-HT2A%20and%20NMDA/1395108a.pdf