Psilocybin For Treatment-resistant Depression

[dfspcc20]

http://www.thelancet.com/pb/assets/raw/Lancet/pdfs/S2215036616300657.pdf

Proof-of-concept study, no control group, so take w/ a grain of salt. But still promising results. I wonder if they'd be able to get past regulations to have a larger study.

It says psilocybin is a serotonin (5-HT) "receptor" agonist. Does that mean it helps speed up serotonin clearance (pretty much the opposite of what SSRIs do, from what I understand)?

 

[snowboard111]

Def: An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response. Whereas an agonist causes an action, an antagonist blocks the action of the agonist and an inverse agonist causes an action opposite to that of the agonist.

"Psilocybin has a novel pharma- cological action in comparison with currently available treatments for depression (ie, 5-HT2A receptor agonism) and thus could constitute a useful addition to available therapies for the treatment of depression. "

 

[dfspcc20]

@snowboard111 Thanks!
From what I gathered, psilocin (from psilocybin) is a direct 5-HT receptor agonist (similar to LSD, no?)
I have pretty much no background in pharmacokinetics, so it takes me a while to wade through these studies.

 

[ddjd]

@snowboard111 Thanks!
From what I gathered, psilocin (from psilocybin) is a direct 5-HT receptor agonist (similar to LSD, no?)
I have pretty much no background in pharmacokinetics, so it takes me a while to wade through these studies.

yes i think they both antagonise 5ht2a

 

[BigYellowLemon]

Serotonergic pyschedelics are biased agonists at most serotonin receptors. They agonize the receptors but the signalling cascade they cause is much different than what serotonin normally does, which is why they're psychedelic and serotonin isn't.

What I think they do is agonize the serotonin receptors in a non-harmful way, but still induce downregulation of the receptors long term, and they shut down serotonin release in the brain by interacting with the raphe nucleus (central module of serotonin in the brain).

If you tried to use serotonin to downregulate the receptors you'd get massive fibrosis and bad effects and serotonin syndrome, so the receptor downregulation wouldn't offset the cost of massive acute serotonin overload.

But because psychedelics activate the receptors differently and cause a very different signalling cascade, you get the same downregulation without the fibrosis and estrogen and nitric oxide release.

So they're like a cheat code for serotonin. The downregulation of serotonin receptors without the actualy damaging effets of serotonin.

As well, the psychedelic experience itself probabaly can have some antidepressant action. Psychedelics completely change the way the brain's circuits are organized. So the limbic system is activating in a way it never has before. Modules that usually never interact directly start creating connections, cortical areas are talking in a different pattern. It completely changes the wiring activity of the brain which ia why it can feel so weird. It can also be responsible for some people becoming"fried" from excessie psyche use, the new channels created are too powerful and the brain organizes itself in a way not conducive to the normal world, in fact not conducive to the way the brain has evolved to be organized in the firat place.

And then there's effects of photons being created by psychedelics, fluorescence, and microtubules, but I have no idea what any of that means.

Psychedelics can be useful as an antidepressant for some but they are not a surefire method. I know so many people who have tripped a ton and are depressed as hell. I really don't think it's that good for that purpose. For some it can be but don't get your hopes up.