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Psilocybin anti-depressant effects occur even when administered with antagonist

Jabberwocky

Jabberwocky

Frumious Bandersnatch
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Nov 3, 1999
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I think I noticed this recently with 2cb. Although the trip itself was far from great, a little scary, and would have been down right traumatic on acid, I've noticed a 70% reduction in depression symptoms, even though I eventually killed the trip off with alprazolam and mirtazapine
 
I'll test the theory and try some out WITH mirtazapine if for some reason the depression ever comes back hard-core.
 
Somehow I theorize that there's more out there about receptors as we know currently. For example, why does buprenorphine precipitate withdrawal while kratom does not. Or why mu opioid rotation works (somewhat). Why switching from one AD to another can re-start the initial waiting period and side effects. Etc.. so many questions un-answered.
Also profiles can differ heavily between in-vitro and in-vivo (imho, maybe these papers where I read that had flaws). So psilocin might still affect other receptors in vivo but not do so in vitro.

Still need to read the paper though, sorry if I touch answered stuff. Will update :)
 
plumbus-nine said:
Somehow I theorize that there's more out there about receptors as we know currently. For example, why does buprenorphine precipitate withdrawal while kratom does not. Or why mu opioid rotation works (somewhat). Why switching from one AD to another can re-start the initial waiting period and side effects. Etc.. so many questions un-answered.
Also profiles can differ heavily between in-vitro and in-vivo (imho, maybe these papers where I read that had flaws). So psilocin might still affect other receptors in vivo but not do so in vitro.

Still need to read the paper though, sorry if I touch answered stuff. Will update :)
Click to expand...
We have explored only 80% of the oceans.

I think that's a good analogy as to where we are at with our understanding of the universe, neuroscience, consciousness etc...

Medical science has always been a "best guess" type of science more than anything other type. Its a bit weird how little we know about how our own brains work really.
 
plumbus-nine said:
…why does buprenorphine precipitate withdrawal while kratom does not…
Click to expand...
I, by and large, find myself whole-heartedly concurring with the sentiments raised in your post (that we can never over-estimate the scope of our own lack with regard of the "unknown unknowns" which could conceivably exist, or engender within ourselves too great a sense that the standards with which the cutting edge defines its expertise is but a partial & incomplete knowledge, no matter how relatively grand the scheme is, that the potential for what we might hone in the field of chemical neuroscience could be ever more complex or that its roots may reach to undermining our foundations now)

That said, this that I quoted above interests me. Does 7-hydroxymitragynine (or another active component of Kratom) display partial inverse agonism in its docking or the manner in which the molecule overlays? It is my understanding that the seventeen position off the nitrogen plays a role in this, and 7-hydroxymitragynine shares instead what would align to the distinctive seven position of buprenorphine, that this trait is oft times common to the orvinol & thevinol 'Bentley' compounds, but hasn't - to the best of my knowledge - anything to do with the mixed (ant)agonism of the drug with regard to the 17—position, only the 7—.
 
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