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A #stablethread on the 5HT2A receptor.
This is the serotonin receptor that is being acted upon whenever someone takes a tryptamine psychedelic (LSD, DMT, etc). Let's get into it!
This is the serotonin receptor that is being acted upon whenever someone takes a tryptamine psychedelic (LSD, DMT, etc). Let's get into it!
It's difficult to talk about the receptors without mentioning the neurotransmitters that enter the receptors so here is a thread on the neurotransmitters: https://twitter.com/StewartalsopIII/status/1321423529590640645
And here is more info on higher-level neuroanatomy for understanding what exactly a neuron is and why the neurotransmitters matter for the functioning of a neuron: https://twitter.com/StewartalsopIII/status/1323250734914293762
Now to get into the 5HT2A receptor.
I'll be taking notes here about this video as I watch it. As with many academic conferences, the speakers could do with some communication training to get their message across effectively, but let's decipher anyway:
I'll be taking notes here about this video as I watch it. As with many academic conferences, the speakers could do with some communication training to get their message across effectively, but let's decipher anyway:
The most interesting thing I've learned so far:
All the tryptamine psychedelics that act on this receptor (agonists) also act on other receptors. The hunt for most scientists is how to find a compound that acts only on the single receptor to see exactly what is happening.
All the tryptamine psychedelics that act on this receptor (agonists) also act on other receptors. The hunt for most scientists is how to find a compound that acts only on the single receptor to see exactly what is happening.
This compound does not exist right now! We are left only with the unprecise tryptamine psychedelics that nature and chemistry have given to us in order to understand the precise role of the 5HT2A receptor.
Apparently, Mescaline is the most specific of the tryptamines, it has the most affinity (lots of neurotransmitters go through it) with the 5TH2A receptor. They used imaging of pig's brains to find out where in the brain and body has the highest density of 5HT2A receptors.
They then repeated the tests with human brains and found that lots of the 5TH2A receptors are in the cortex.
Here is more on the cortex (the first four lobes make up the cortex): https://twitter.com/StewartalsopIII/status/1322943340854345728
Here is more on the cortex (the first four lobes make up the cortex): https://twitter.com/StewartalsopIII/status/1322943340854345728
That video was either too focused on unimportant technicalities or was too far over my head.
I finally found someone who can speak clearly. This video makes the claim that the 5HT2A receptor is important for predictive processing and percepion:
I finally found someone who can speak clearly. This video makes the claim that the 5HT2A receptor is important for predictive processing and percepion:
Briefly, predictive processing is an organism's ability to take past states (our conditioning) and mix them with current sensory inputs in order to predict what will happen next in our immediate environment.
This predictive processing is a top-down phenomenon, not a bottom up. Our cortex is predicting is mostly responsible for what will happen next and is projecting those predictions down to the sensory organs (eyes, ears, skin, etc)
This is important for understanding the 5HT2A receptor because, while these receptors are everywhere, they are a lot of them in the cortex where this predictive processing is done.
If you have ever taken psychedelics remember how total the experience was.
If you have ever taken psychedelics remember how total the experience was.
She says that there are relatively more 5HT2A receptors in the frontal cortex and the visual cortex, but relatively less in the motor cortex. Again, think about how psychedelics changed the way you saw reality and the way you thought about it, not necessarily how you moved in it.
The juice of what she is arguing is that psychedelics target the 5HT2A receptor in such a way that they disrupt the predictions that feel normal to us (create the ego) and start sending a bunch of new predictions that are novel in ways that radically change our perception.
Pyramidal cells work in different regions of the brain work together in order to give us this sense of stability when perceiving reality (a very convincing illusion). We can measure these cells using imaging. 5HT2A agonists (psychedelics) disrupt this https://twitter.com/StewartalsopIII/status/1332359452058587138
Another core argument she is making is that the default state that we are in that seems so real is based on our history and thus it misses tons of stimuli in our environment that could be useful but we ignore them because of biases. Psychedelics open up the doors of perception
This is why someone who takes psychedelics might have profound insights into their own behavior or their relationship with the world. These insights normally wouldn't have seemed important enough because of our habitual patterns of existence.
She brings an interesting point about depression (remember we are talking about serotonin receptors) which is that the predictive processing is too stable and those of us with it get stuck in a circular hell where our predictions get reinforced in higher abstract cortical areas.
This is why psychedelics might be so effective at treating depression. Many pharmaceuticals are created because they DONT have psychoactive effects. But maybe the psychoactive effects are important for breaking one out of the self-reinforcing circular patterns of negativity.
