Effects of psilocybin and related compounds on cerebroprotection during ischemic stroke (Stage 1 Registered Report)
OpenAlex – November 17, 2025
Source: OpenAlex
Summary
Psilocybin and related compounds may protect brain cells after ischemic stroke, a leading cause of death and disability. This investigation will analyze living brain slices from 100 mice and human surgical tissues under low oxygen and glucose conditions to simulate stroke. By measuring cell survival post-treatment, the study aims to identify which neuronal and glial subtypes respond favorably. Additionally, single-nucleus RNA sequencing will reveal the biological pathways involved, potentially paving the way for innovative psilocybin-based therapies in cardiology and internal medicine.
Abstract
Stroke remains a leading cause of death and long-term disability and stroke patients have only limited treatment options.Recent preclinical evidence suggests that psychedelics such as psilocybin may confer cerebroprotection by engaging serotonin (5-HT) receptor pathways, yet their cellular targets and translational potential remain poorly understood.Here, we propose to systematically evaluate psilocybin and related tryptamine analogs for cerebroprotective effects in ischemic mouse and human brain tissue.Using an ex vivo oxygen-glucose deprivation (OGD) model combined with automated imaging and single-nucleus RNA sequencing, we will quantify compound-specific protection, identify responsive neuronal and glial subtypes, and map conserved signaling networks in mice and human.This study will dissect the molecular and cellular pathways through which psilocybin and related tryptamines may promote cerebroprotection in stroke.Additionally, these findings may support the development of future psilocybin-related therapies. Lay summary:In this registered report we plan to test whether psilocybin-like compounds can protect brain cells after stroke.We use living brain slices from mice and from human surgical tissue, place them under low oxygen and glucose to mimic stroke, and then measure how many cells survive after treatment.We then use single nucleus RNA sequencing to determine which cell types respond and which biological pathways are involved.