Topic starter
There is a new scientific article which examines how psilocybin affects blood flow to the brain, and what role the 5-HT2A receptor may play in it.
In it, we discuss:
The researchers compared the acute effects of psilocybin and ketanserin in a single-blind crossover study in 28 healthy participants. Psilocybin acts as an agonist on the 5-HT2A receptor, while ketanserin is an antagonist. Using MRI techniques, the authors looked at changes in cerebral blood flow and the diameter of the arteria carotis interna, i.e. a major artery that carries blood to the brain.
The real focus of this article is not on clinical improvement in depression or other conditions, but on the direct neurophysiological effects of psilocybin in healthy people. In doing so, the authors also investigated whether blood levels of psilocin and the subjective intensity of the experience correlated with changes in blood flow.
The results show that higher psilocin levels and stronger subjective drug experience were clearly associated with lower regional and global cerebral blood flow. Around the peak effect, blood flow dropped by about 11.6 per cent on average under psilocybin. After ketanserin, the researchers saw no significant change in cerebral blood flow.
The authors also found that psilocybin significantly reduced the diameter of the internal carotid artery. This decreased by about 10.5 per cent, while ketanserin had practically no effect. According to the authors, this is the first in-vivo human evidence that psilocybin narrows this artery. This is important because it helps to better understand how psilocybin acutely affects the brain.
Importantly, however, this study was conducted in healthy volunteers and says nothing about therapeutic efficacy in patients. In addition, the article shows an acute physiological change, but not automatically whether that change is favourable, unfavourable or therapeutically relevant in clinical context.
In one sentence, this article shows that psilocybin in healthy people temporarily lowers cerebral blood flow and constricts the internal carotid artery, while ketanserin does not.
Spoiler
New article description
Abstract
Psilocin, the active metabolite of psilocybin, is a psychedelic and agonist at the serotonin 2A receptor (5-HT2AR) that has shown positive therapeutic effects for brain disorders such as depression.
To elucidate the brain effects of psilocybin, we directly compared the acute effects of 5-HT2AR agonist (psilocybin) and antagonist (ketanserin) on cerebral blood flow (CBF) using pseudo-continuous arterial spin labelling magnetic resonance imaging (MRI) in a single-blind, cross-over study in 28 healthy participants. We evaluated associations between plasma psilocin level (PPL) or subjective drug intensity (SDI) and CBF.
We also evaluated drug effects on internal carotid artery (ICA) diameter using time-of-flight MRI angiography. PPL and SDI were significantly negatively associated with regional and global CBF (∼11.6% at peak drug effect, p < 0.0001). CBF did not significantly change following ketanserin (2.3%, p = 0.35). Psilocybin induced a significantly greater decrease in CBF compared to ketanserin in the parietal cortex (pFWER < 0.0001).
ICA diameter was significantly decreased following psilocybin (10.5%, p < 0.0001) but not ketanserin (-0.02%, p = 0.99). Our data support an asymmetric 5-HT2AR modulatory effect on CBF and provide the first in vivo human evidence that psilocybin constricts the ICA, which has important implications for understanding the neurophysiological mechanisms underlying its acute effects.
Keywords: Psilocybin; psilocin; cerebral blood flow; ketanserin; 5-HT2A receptor; MRI; internal carotid artery.
Posted : 18 March 2026 15:00