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I realize my question is more of a pharmacological one than a neuroscientific one, but I didn't know where else to ask this question.

As far as I've read, there's two components to how psychedelics work:

  1. Psychedelics agonise serotonin 2A receptors. This causes an over-saturation of serotonin in the brain, which causes the effects.

  2. Psychedelics reduce blood flow to the DMN (default mode network), which reduces its supply of oxygen, and therefore its activity. That makes the brain redirect the neural activity out to the "fringes" of the brain, which causes signals to travel new paths. These new paths often involve different parts of the brain that wouldn't usually communicate. This causes synesthesia, new perspectives and a generally just a very altered mental and visual perception.

Now, is it so that both, neither or only one of these explanations are correct? Perhaps it is the over-saturation of serotonin that reduces the blood flow to the DMN?

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    $\begingroup$ Can you link your sources? I've never come across the DMN mechanism you mention. I would like to have a look at it. $\endgroup$
    – AliceD
    Commented Jan 30, 2021 at 18:11
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    $\begingroup$ @AliceD I'm guessing OP (or their source) misinterpreted the direction of causality in an fMRI result, probably a paper by Carhart-Harris. Katrin Preller sees different results, though, as far as I remember. $\endgroup$
    – Bryan Krause
    Commented Jan 30, 2021 at 18:19
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    $\begingroup$ Possible duplicate of What is the Mechanism of 5-HT2A-mediated psychedelia? $\endgroup$
    – Arnon Weinberg
    Commented Jan 30, 2021 at 20:21
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    $\begingroup$ You probably read about a paper using fMRI to image brain activity. fMRI uses blood oxygenation to infer brain activity, because the vasculature adjusts to deliver more blood to metabolically active areas. So it wouldn't be that psychedelics are altering blood flow, but they are changing brain activity and we can measure this looking at blood oxygenation. Pyramidal cells are excitatory neurons in cortex. If you can't understand the linked answer it's probably better to start learning about neuroscience more generally rather than starting with psychedelics. $\endgroup$
    – Bryan Krause
    Commented Jan 31, 2021 at 21:47
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    $\begingroup$ You could start with Carhart-Harris, R. L., Erritzoe, D., Williams, T., Stone, J. M., Reed, L. J., Colasanti, A., ... & Nutt, D. J. (2012). Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proceedings of the National Academy of Sciences, 109(6), 2138-2143. $\endgroup$
    – Bryan Krause
    Commented Feb 1, 2021 at 17:21

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