Psychedelics mediate their mind-altering effects my activation of serotonin 2A (5-HT2A) receptors. 5-HT2A receptors are proteins that are abundantly expressed by so-called pyramidal cells of the brain’s cortex. It is these pyramidal-cellular 5-HT2A receptors, which in fact are thought to constitute the “molecular doorway” for the psyche to enter psychedelia.
However, 5-HT2A receptors are by far not restricted to cortical pyramidal cells. They can be found in a lot of other regions of the mammalian central nervous system and the periphery; in the spinal cord, the retina, the liver, the intestines, the platelets, the vessels, and even in the bones. What do 5-HT2A receptors do here and beyond the brain in general?
Although it is unlikely that all of these non-brain 5-HT2A populations play a role in psychedelia, chances are that they play out in the overall physiology as the psychedelic travels the body. But let us take a step back and reconsider a 5-HT2A function that is more imminent to the brain (and thus psychedelia?):
Using 25CN-NBOH (a mescaline-derivative which selectively activates 5-HT2A receptors), we in our most recent research show how 5-HT2A receptors affect different parameters of blood-blow in brain-supplying neck-arteries. Mind you blood does not only carry oxygen and nutrition to the brain, but also distributes cell-derived warmth across the body. It might therefore not be surprising if environmental temperature conditions did have some say in psychedelic blood flow regulation, too…
Green open access. Enjoy :)