I wonder, why do we have 5ht2a receptors inside our neurons if our natural neurotransmitters like serotonin would never reach them due to their polarity? And why would triggering them cause psychedelic effects / dendritic growth? And are the subjective effects and dendritic growth unrelated effects of the stimulus, or do the subjective effects cause the dendritic growth (or vice versa)?
I'm assuming that when we're young and our brains are developing we experience a lot of dendritic growth- what causes that? Is it activation of the same receptors, and if so what is activating them?
Such a great distillation and explanation of that paper, Andrew. I had been meaning to get round to it but other things got in the way. Inspiring read for my Friday morning (distracting me from work) haha :) I have to admit, I wasn't aware of intracellular 5HT-2A receptors before this so it was something of a personal paradigm shift.
Maybe this answers my previous comment - anecdotally it seems that LSD has a "long LSD" effect of years or even a lifetime. However anecdotes need real experiments to be believed.
What future experiments would you like to see? Are there techniques that or models that the authors could have used? Or what would you like to see next from this line of thinking?
Andrew are you familiar with this old 1979 paper claiming that DMT was identified in the urine of patients demonstrating symptoms of psychosis? The authors are clearly looking for a source of psychosis but a more interesting hypothesis is that DMT is potentially acting as a mood stabilizer, as it is noted to dissipate in urine as clinical symptoms disappear. It would be very interesting, cheap, and easy to attempt to replicate this work.
my peak experiences feel completely different than a normal breakthrough. the feel more like a hijacking of my consciousness than me inhabiting a space. I also completely forget the appearance of the entities, which as become an ongoing joke for them.
5ht2a is postulated as the mechanism of psychedelic experience because, when blocked, the experience doesn't occur. What this means is that it is a necessary condition for the experience, but 5ht2a activation alone does not explain the experience, it is not a sufficient condition. Neuroplasticity is also not sufficient as much of the phenomenological brunt of the experience and subsequent meaningfullness occurs in the blink of an eye. If anything, this can only be explained in the context of gestalt psychology whereby psychedelics catalyse the psychological gestalt shift or seeing as. synaptic reductionist explanation cannot account for the profundity and immediacy of the psychological phenomenon I think.
Amazing breakdown, thank you!
I wonder, why do we have 5ht2a receptors inside our neurons if our natural neurotransmitters like serotonin would never reach them due to their polarity? And why would triggering them cause psychedelic effects / dendritic growth? And are the subjective effects and dendritic growth unrelated effects of the stimulus, or do the subjective effects cause the dendritic growth (or vice versa)?
I'm assuming that when we're young and our brains are developing we experience a lot of dendritic growth- what causes that? Is it activation of the same receptors, and if so what is activating them?
Thank you for doing this!
Such a great distillation and explanation of that paper, Andrew. I had been meaning to get round to it but other things got in the way. Inspiring read for my Friday morning (distracting me from work) haha :) I have to admit, I wasn't aware of intracellular 5HT-2A receptors before this so it was something of a personal paradigm shift.
Haha, I suppose this would seem like a "new mechanism" to a lot of people! Thanks for the article;)
Maybe this answers my previous comment - anecdotally it seems that LSD has a "long LSD" effect of years or even a lifetime. However anecdotes need real experiments to be believed.
I just found your substack via the Twitter algorithm. Absolutely fantastic breakdown. Thanks!
Thank you for the great breakdown of the article!
What future experiments would you like to see? Are there techniques that or models that the authors could have used? Or what would you like to see next from this line of thinking?
https://pubmed.ncbi.nlm.nih.gov/286576/
Andrew are you familiar with this old 1979 paper claiming that DMT was identified in the urine of patients demonstrating symptoms of psychosis? The authors are clearly looking for a source of psychosis but a more interesting hypothesis is that DMT is potentially acting as a mood stabilizer, as it is noted to dissipate in urine as clinical symptoms disappear. It would be very interesting, cheap, and easy to attempt to replicate this work.
Andrew, would combining Niacin with psychedelics still result in neuroplasticity but without the psy effects?
https://bibliography.maps.org/citation/261
my peak experiences feel completely different than a normal breakthrough. the feel more like a hijacking of my consciousness than me inhabiting a space. I also completely forget the appearance of the entities, which as become an ongoing joke for them.
5ht2a is postulated as the mechanism of psychedelic experience because, when blocked, the experience doesn't occur. What this means is that it is a necessary condition for the experience, but 5ht2a activation alone does not explain the experience, it is not a sufficient condition. Neuroplasticity is also not sufficient as much of the phenomenological brunt of the experience and subsequent meaningfullness occurs in the blink of an eye. If anything, this can only be explained in the context of gestalt psychology whereby psychedelics catalyse the psychological gestalt shift or seeing as. synaptic reductionist explanation cannot account for the profundity and immediacy of the psychological phenomenon I think.