How does psilocybine induce hallucinations via serotonin??

[JohnBoy2000]

I'm just looking into the anti-depressant properties of magic shrooms, and apparently their primary effect is via 5HT2A.

Agonist at this receptor - so - isn't it typically dopamine that's associated with hallucinations?

Is there any more profound insight as to how shrooms have AD effects?

Also - historical AD's act on the three monoamines; shrooms doesn't actually effect noradrenaline, does it?

 

[dopamimetic]

Most of the tryptamines and some phenethylamines induce pseudo-hallucinations - (especially beautiful visual ones - CEV and OEVs) via the 5-HT2a route so its pretty common ... dopamine is involved in psychotic hallucinations, yes but that's not exactly the same (afaik - correct me if I'm wrong!).. too much 5-HT2a is considered dysphoric but a bit seems to be anti-depressant and also the receptor downregulates with both psychedelics and SSRIs. Real hallucinations can be caused by e.g. muscarinic antagonism (scopolamine etc).

 

[sekio]

James Kent wrote a whole book on how serotonergics psychedelics produce their visual distortions/hallucinations. The current best explanation involves the 5-HT2a receptor as part of the system responsible for dynamic range adjustment of sense data. Psychedelics end up forcing the activation of 5HT2a and thereby increasing the "gain" on e.g. visual data, producing patterns and distortions from overamplification of sense data.

 

[novaveritas]

I'm just looking into the anti-depressant properties of magic shrooms, and apparently their primary effect is via 5HT2A.

Agonist at this receptor - so - isn't it typically dopamine that's associated with hallucinations?

Is there any more profound insight as to how shrooms have AD effects?

Also - historical AD's act on the three monoamines; shrooms doesn't actually effect noradrenaline, does it?

The concept that Dopamine= whatever Serotonin = whatevever Norepinephrine= whatever is the Monoaminergic hypothesis of mood disorder which has its genesis in the 40s and 50s discovery of the central monoamines, When people discover hammers everything looks like nails especially if they have hammers to sell. The monoaminergic hypothesis was a terrible oversimplification when it was first proposed and still is. If the monoaminergic hypothesis was correct then why are most monoaminergic antidepressants SSRIs SDNRIs or whatever variation only slightly more effective than placebo if they are effective at all?

Throw out the dopamine serotonin norepinephrine theories they were always just vaguely plausible stories which were seized upon by marketing departments and popular science.


It seems it is more likely that all antidepressants work by causing (general) disruption of brain function which in turn allows rewiring and exit of the depressive loops. This explains why ECT works though it is very clumsy and poorly targeted. It also explains why psychedelics can both generate and treat depressive disorders. Psychedelics essentially inhibit existing thought patterns, facilitate new thought patterns and synaptic plasticity and neurogenesis and so forth possibly disrupting the patterns that were leading to the depressive state. Equally they could create a new depressive state. Shake it all up and the brain will reorder and possibly get out of the depressive state. It really doesn't matter what does the shaking. There is not a grand unified theory of depression that works.

Take James L Kent and anything he writes with a pinch of salt if you are after coherent answers, he has spend years trying to find a niche for shamanism and integrating hippy woo bullshit into some kind of scientific framework whilst adding a generous portion of fractal and chaos theory for good measure and it doesn't hang together at all. Kents book was written in 2010 but the key papers blowing the pharmacology out of the water are from the late 1990s, Kents book is still an interesting read just don't expect the answers to be right or make any overall sense.

There is speculation that psychedelic hallucination is the result of tuning the brain to receive cosmic radiation at a wider bandwidth than normal; bands
associated with electromagnetic, metaphysical, morphogenetic, Akashic, or geomagnetic fields. This so-called spectral argument posits that instead of producing consciousness, the human brain acts as a radio receiver for consciousness, and psychedelics allow the user to tune the brain to new perceptual frequencies, possibly higher dimensional in nature

Monoamines entering the bloodstream are normally kept out of the brain by the blood-brain-barrier, but psychedelic molecules have a neutral charge so they are able to pass. When these amine crystals pass through the blood-brain barrier they brush against neural receptor sites; if the receptors are a good fit then the crystals get stuck for a short
period of time.

yeah cosmic rays and crystals groovy baby

 

[AlphaMethylPhenyl]

Wouldn't be absurd to suggest a mechanism that leads to chronic down-regulation of 5-HT2a.

 

[emkee_reinvented]

James Kent wrote a whole book on how serotonergics psychedelics produce their visual distortions/hallucinations. The current best explanation involves the 5-HT2a receptor as part of the system responsible for dynamic range adjustment of sense data. Psychedelics end up forcing the activation of 5HT2a and thereby increasing the "gain" on e.g. visual data, producing patterns and distortions from overamplification of sense data.

Some hallucinations do seem to have a logical explanetion. What I am guessing Kent found out about the patterns being results of amplification.

But I had these patterns appear in sand, broad day light, and my co tripper was experiencing them at the same time. That was weird as shared hallucinations was new to me.
Weirdly enough, as we were updating what we saw at the same time, they were synchrone, to us, from the moment we paid attention to test the hypothesis. Hardly proof but intriging.

My thinking is that it could have had to do with the bloodflow rhytm that very alike between people.