Acute psilocybin and ketanserin effects on cerebral blood flow: 5-HT2AR neuromodulation in healthy humans.
Kristian Larsen, Ulrich Lindberg, Brice Ozenne, Drummond E McCulloch, Sophia Armand, Martin K Madsen, Annette Johansen, Dea S Stenbæk, Gitte M Knudsen, Patrick M Fisher
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism February 26, 2025 DOI: 10.1177/0271678x251323364 via PubMed
Summary
AI-generated from the abstractPsilocybin, the active compound in magic mushrooms, reduces blood flow in the brain. In a study of 28 healthy volunteers, psilocybin decreased cerebral blood flow by about 11.6% at peak effect, while the serotonin blocker ketanserin had no significant effect. Psilocybin also constricted the internal carotid artery by 10.5%, whereas ketanserin did not. These findings suggest that psilocybin's effects on brain blood flow involve the serotonin 2A receptor and may help explain its therapeutic potential for conditions like depression.
Study at a glance
| Characteristics | Single-blind, cross-over study Peer reviewed |
|---|---|
| Sample size | 28 |
| Population | Healthy participants |
| Interventions | Psilocybin Ketanserin |
| Topics | Psilocybin |
| Keywords | Psychedelics hallucinogens Entheogens Psychedelic drugs Brain imaging neuroimaging MRI |
| Citations | 9 |
| Key finding | Psilocybin significantly decreased cerebral blood flow and constricted the internal carotid artery, while ketanserin had no such effects, indicating a serotonin 2A receptor-mediated mechanism. |
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 labeling 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.