Psychedelic 5-HT2A activity drives blood volume in brain-supplying arteries

What is it about?

Psychedelics are thought to mediate their mind-altering effects my activation of serotonin 2A (5-HT2A) receptors located on cortical pyramidal cells of the brain. However, 5-HT2A receptors are by far not restricted to cortical pyramidal cells. They can be found in various 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.

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Photo by JR Korpa on Unsplash

Photo by JR Korpa on Unsplash

Why is it important?

The effects of psychedelics on the human brain are often investigated via PET and fMRI, which measure vascular blood flow parameters to make inferences about the neurons supplied by the blood. As psychedelics are vasoactive (i.e., they influence the diameter of vessels), it appears pivotal to delineate which PET/fMRI-measured brain effects are truly neuronal in nature or just secondaries of psychedelic vasoactivity. Here, understanding of brain as well as systemic haemodynamics will need to be integrated.

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