Effects of psilocybin and related compounds on cerebroprotection during ischemic stroke (Stage 1 Registered Report)
Ruslan Rust
November 17, 2025 DOI: 10.55277/researchhub.6rz9605v.1 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Registered report (preclinical ex vivo study with OGD model and single-nucleus RNA sequencing) |
|---|---|
| Population | Mouse and human brain tissue (ex vivo slices) |
| Interventions | Psilocybin related tryptamine analogs |
| Topics | Psilocybin |
| Keywords | Ischemic stroke Cardiology Anesthesia Stroke engine Ischemia |
| Key points | The study proposes to systematically evaluate psilocybin and related tryptamine analogs for cerebroprotective effects in ischemic mouse and human brain tissue. |
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.
Comparable studies
Other preclinical and animal studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice Mice | 2021 | Experimental study | |
| Psychedelics reopen the social reward learning critical period Mice | 2023 | Experimental study in mice | |
| Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. C57BL/6J mice | 2020 | Experimental study with dose-response experiments | |
| Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning Mice | 2013 | Experimental study |