<p>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.</p>
<p>As far as I've read, there's two components to how psychedelics work:</p>
<ol>
<li><p>Psychedelics agonise serotonin 2A receptors. This causes an over-saturation of serotonin in the brain, which causes the effects.</p>
</li>
<li><p>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 &quot;fringes&quot; 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.</p>
</li>
</ol>
<p>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?</p>

CC BY-SA 4.0
2021-01-30T18:11:18.983Z
Can you link your sources? I've never come across the DMN mechanism you mention. I would like to have a look at it.
AliceD
CC BY-SA 4.0
2021-01-30T18:19:08.960Z
@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.
Bryan Krause
CC BY-SA 4.0
2021-01-30T20:17:31.260Z
@BryanKrause - fascinating. I'll take a look, thanks.
AliceD
CC BY-SA 4.0
2021-01-30T20:21:22.893Z
Possible duplicate of [What is the Mechanism of 5-HT2A-mediated psychedelia?](https://psychology.stackexchange.com/q/3799/7001)
Arnon Weinberg
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2021-01-31T20:42:25.040Z
@BryanKrause The linked answer was formulated in a  completely Greek way to me I'm afraid. I've made a checklist of the things that I need to learn about to understand their answer, and currently I'm still wondering how pyramidal cells work. How are they different from other neurons, what is their function, etc. I cannot remember where I read this stuff about the DMN, but I'll read some stuff from Carhart-Harris since you mentioned it, and I'd like to know what I got wrong with that explanation. Is it far from the truth, or is the DMN  involved in the explanation of psychedelic experiences?
A. Kvåle
CC BY-SA 4.0
2021-01-31T20:44:03.393Z
@ArnonWeinberg The linked answer was formulated in a  completely Greek way to me I'm afraid. I've made a checklist of the things that I need to learn about to understand their answer, and currently I'm still wondering how pyramidal cells work. How are they different from other neurons, what is their function, etc. I cannot remember where I read this stuff about the DMN. I'd like to know what I got wrong with that explanation. Is it far from the truth, or is the DMN  involved in the explanation of psychedelic experiences?
A. Kvåle
CC BY-SA 4.0
2021-01-31T21:47:14.253Z
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.
Bryan Krause
CC BY-SA 4.0
2021-02-01T07:58:07.773Z
@BryanKrause Okay, so they're not reducing blood flow to the DMN, but they are still reducing the activity in the DMN? Or at least, the fMRI would suggest so?
A. Kvåle
CC BY-SA 4.0
2021-02-01T14:59:07.570Z
There is at least one paper by one research group showing that, yes. We don't really know for sure though. One problem is that psychedelics have direct effects on blood flow as well, and this can impact fMRI. Different researchers account for this in different ways and they get different results when they do so. There is a lot of argument about which is better.
Bryan Krause
CC BY-SA 4.0
2021-02-01T17:15:06.323Z
@BryanKrause Interesting, could you perhaps link to the paper you're thinking of? From that paper I'll probably find other papers on the same subject and see the different angles and then the different arguments for which interpretation is most likely.
A. Kvåle
CC BY-SA 4.0
2021-02-01T17:21:23.737Z
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.
Bryan Krause
CC BY-SA 4.0
2021-02-01T17:30:55.137Z
@BryanKrause I didn't know David Nutt had written on this, I've already talked some to him in relation to this dissertation. Thank you for the names, I will check all of this out once I've learned enough general neuroscience.
A. Kvåle
<brain><psychopharmacology><serotonin><synesthesia>
How do psychedelics work?
A. Kvåle
# How do psychedelics work?

(Asked by: username_0 on 2021-01-30)

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?

**Tags:** brain, psychopharmacology, serotonin, synesthesia

> **Comments:**
> **username_1**: Can you link your sources? I've never come across the DMN mechanism you mention. I would like to have a look at it.  
> **username_2**: @username_1 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.  
> **username_1**: @BryanKrause - fascinating. I'll take a look, thanks.  
> **username_3**: Possible duplicate of [What is the Mechanism of 5-HT2A-mediated psychedelia?](https://psychology.stackexchange.com/q/3799/7001)  
> **username_0**: @BryanKrause The linked answer was formulated in a  completely Greek way to me I'm afraid. I've made a checklist of the things that I need to learn about to understand their answer, and currently I'm still wondering how pyramidal cells work. How are they different from other neurons, what is their function, etc. I cannot remember where I read this stuff about the DMN, but I'll read some stuff from Carhart-Harris since you mentioned it, and I'd like to know what I got wrong with that explanation. Is it far from the truth, or is the DMN  involved in the explanation of psychedelic experiences?  
> **username_0**: @ArnonWeinberg The linked answer was formulated in a  completely Greek way to me I'm afraid. I've made a checklist of the things that I need to learn about to understand their answer, and currently I'm still wondering how pyramidal cells work. How are they different from other neurons, what is their function, etc. I cannot remember where I read this stuff about the DMN. I'd like to know what I got wrong with that explanation. Is it far from the truth, or is the DMN  involved in the explanation of psychedelic experiences?  
> **username_2**: 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.  
> **username_0**: @BryanKrause Okay, so they're not reducing blood flow to the DMN, but they are still reducing the activity in the DMN? Or at least, the fMRI would suggest so?  
> **username_2**: There is at least one paper by one research group showing that, yes. We don't really know for sure though. One problem is that psychedelics have direct effects on blood flow as well, and this can impact fMRI. Different researchers account for this in different ways and they get different results when they do so. There is a lot of argument about which is better.  
> **username_0**: @BryanKrause Interesting, could you perhaps link to the paper you're thinking of? From that paper I'll probably find other papers on the same subject and see the different angles and then the different arguments for which interpretation is most likely.  
> **username_2**: 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.  
> **username_0**: @BryanKrause I didn't know David Nutt had written on this, I've already talked some to him in relation to this dissertation. Thank you for the names, I will check all of this out once I've learned enough general neuroscience.  

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## 0 answers

