• Members of the previous forum can retrieve their temporary password here, (login and check your PM).

Psilocybin, a neural connectivity paradox

Migrated topic.
Nathanial.Dread said:
It's a little more complicated then that. LSD and lisuride are both agonists, but they produce different transcriptional patterns and activate different post-synaptic signaling pathways.
This paper details a lot of that stuff. You'll notice that the genes induced by LSD but not lisuride are early growth hormones involved in neurogenesis and neuroplasticity. I think that this is a key piece of the puzzle, since activation of those genes may have all kinds of effects on global information processing.

It may be that the 5-HT2Ar has two different 'on' conformations, which are triggered by different agonists. How exactly this difference in signalling happens is unknown at the moment though.

It's actually unknown whether 5-HT itself elicits the psychedelic or non-psychedelic signaling pathway. My hunch is that it doesn't.

These cortical 5-HT2Ars also form oligomer complexes with metabotropic glutamate receptors, and the cross-talk also has been shown to play a role in the etiology of psychedelic effects, so in addition to looking at the serotonergic system, we also need to look at the glutamatergic system as well.

Blessings
~ND
Click to expand...

This is amazing!

I have some catching up to do, sorry I'm learning all this on the fly.

Why does it seem that every action which is necessary is not sufficient?

Why is it that you can "turn off" the raphe nucli, agonize the 5HT2A/C receptors, which connect the thalamus and the cortex regions, induce thalamic gating, and so on, but still fail to produce psychedelia?...


These alpha-helical proteins that compose the 5HT2A/C receptor fascinate me, there are 7 helices, now, serotonin "fits" each alpha-helical protein in a specific shape, now, say you have a compound which is similar to serotonin, but has additional atomic structures, these additional structures will hit the helices in a unique way, say bending helices 4 and 7 into a different shape, which produces a signal and function similar to serotonin, acting on a serotonin receptor, but is unique as the helices are bent into a new shape...

These receptors are not just on/off switches, this is where selectivity comes into play...

This link is for a paper regarding Serotonin Receptor Subtypes and Ligands (Richard A. Glennon, Malgorzata Dukat and Richard B. Westkaemper) it's fascinating stuff...


...sorry, I know between learning the parts of the brain and their functions, receptor sites, the anatomy and function of receptor sites, and their interactions with various neurotransmitters and chemical compounds...I'm all over the place...

Keep in mind I'm in school for organic chemistry, which is massive amounts of work as well...

I think I'm starting to understand psychedelics and the brain far better though, even just in this conversation I have learned tons...

There's just so many different aspects to investigate, each one intricate as the last...

-eg
 
Back
Top Bottom