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What would be fascinating is to reconcile how dissociatives (Ketamine, Salvia, etc) and psychedelics (LSD, psilocybin, DMT, etc) produce a similar end-states,

What would be fascinating is to reconcile how dissociatives (Ketamine, Salvia, etc) and psychedelics (LSD, psilocybin, DMT, etc) produce a similar end-states, despite operating primarily on different classes receptors, and most fascinatingly, having the _opposite_ "high-level" effects on the brain! Psychedelics operate primarily on serotonin (5HT2A) receptors, and are said to "increase connectivity" and brain activity when measured via fMRI. Dissociatives, on the other hand, operate on NMDA receptors, and _decrease_ brain activity when studied. While the actual qualitative experience may differ, it's fascinating how "more connectivity" and "less connectivity" both lead to the same place - ego death, depersonalization, feelings of connectivity and one-ness, experiences of seeing gods/aliens/the universe, etc.

type0 6y ago
> "more connectivity" and "less connectivity" It's not "more/less connectivity". It's likely just dis-inhibition of negative feeback loops that leads to the same result. Interesting question is what pharmacology would be best to study consciousness, if or when one could define it.
- oarabbus_ 6y ago
  I'm not sure that is correct. Psilocybin: https://royalsocietypublishing.org/doi/full/10.1098/rsif.2014.0873 https://royalsocietypublishing.org/doi/full/10.1098/rsif.201... https://www.sciencedirect.com/science/article/pii/S1053811920304663 https://www.sciencedirect.com/science/article/pii/S105381192... Ketamine: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461985/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461985/ https://onlinelibrary.wiley.com/doi/full/10.1002/hbm.24791 https://onlinelibrary.wiley.com/doi/full/10.1002/hbm.24791 It is well known that dissociative anaesthetics reduce brain activity and communication between brain regions. Classical psychedelics on the other hand tend to increase global brain activity, including that between regions (i.e. connectivity)

type0 6y ago

> "more connectivity" and "less connectivity" It's not "more/less connectivity". It's likely just dis-inhibition of negative feeback loops that leads to the same result. Interesting question is what pharmacology would be best to study consciousness, if or when one could define it.

oarabbus_ 6y ago
I'm not sure that is correct. Psilocybin: https://royalsocietypublishing.org/doi/full/10.1098/rsif.2014.0873 https://royalsocietypublishing.org/doi/full/10.1098/rsif.201... https://www.sciencedirect.com/science/article/pii/S1053811920304663 https://www.sciencedirect.com/science/article/pii/S105381192... Ketamine: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461985/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461985/ https://onlinelibrary.wiley.com/doi/full/10.1002/hbm.24791 https://onlinelibrary.wiley.com/doi/full/10.1002/hbm.24791 It is well known that dissociative anaesthetics reduce brain activity and communication between brain regions. Classical psychedelics on the other hand tend to increase global brain activity, including that between regions (i.e. connectivity)