Effects of Psilocybin on Mouse Brain Microstructure.
Paloma C Frautschi, Ajay P Singh, Nicholas A Stowe, Sean M. Grady, Zarmeen Zahid, Matthew I Banks, John-Paul J Yu
AJNR. American journal of neuroradiology June 3, 2025 DOI: 10.3174/ajnr.a8634 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Sample size | 36 |
| Population | C57BL/6J male mice aged 11-15 weeks |
| Interventions | Psilocybin 6-fluoro-N N-diethyltryptamine saline |
| Duration | 24 hours and 72 hours posttreatment |
| Topics | Psilocybin |
| Keywords | Psychedelics Brain research Mental health |
| Citations | 2 |
| Key findings | Psilocybin induced microstructural and connectivity differences in the frontal association cortex, primary visual cortex, striatum, and hippocampus of male mice at 24 and 72 hours posttreatment. |
Abstract
There is surging interest in the therapeutic potential of psychedelic compounds like psilocybin in the treatment of psychiatric illnesses like major depressive disorder (MDD). Recent studies point to the rapid antidepressant effect of psilocybin; however, the biologic mechanisms underlying these differences remain unknown. This study determines the feasibility of using diffusion MRI to characterize and define the potential spatiotemporal microstructural differences in the brain following psilocybin treatment in C57BL/6J male mice. Eleven- to 15-week-old C57BL/6J male mice were randomly assigned to receive psilocybin, 6-fluoro-N, N-diethyltryptamine, or saline and ex vivo imaged 24 hours (n=18) and 72 hours (n=18) posttreatment. A 1-way ANOVA with multiple comparison testing (Bonferroni correction) assessed diffusion metric differences (tractography, DTI, neurite orientation dispersion and density imaging) between the 3 groups and was performed in the following regions of interest: amygdala, striatum, hippocampus, thalamus, primary visual cortex area, frontal association cortex, and medial prefrontal cortex at 24 hours and 72 hours postdrug administration. Psilocybin-treated mice demonstrated structural connectivity differences at 72 hours in the frontal association cortex (compared with saline, mean tract length increases, P = .03). Psilocybin also induced microstructural differences at 24 hours postinjection in the primary visual cortex (compared with saline, mean diffusivity [MD] increases, P = .02) and 72 hours postinjection in the striatum (compared with saline; MD increases, P = .02, neurite density index [NDI] decreases, P = .02) and hippocampus (compared with saline; MD increases, P = .04, NDI decreases, P = .02). Diffusion microstructure imaging and white matter tractography are sensitive methods to detect and characterize the neural substrates and microstructural differences accompanying psilocybin treatment. These findings suggest the potential role for diffusion microstructure imaging to quantify the bioeffects of psychedelics like psilocybin on the brain, monitor treatment response, and identify salient clinical end points in an emerging therapeutic option for patients with MDD.
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 |
Citations in the library
Cited by 2
- Study Protocol for "Exploring the safety and therapeutic potential of psilocybin in the treatment of anorexia nervosa in adolescents and young adults". PLoS One June 30, 2026
- Potential molecular pathways and therapeutic implications of rapid-acting antidepressants on myelin biology: a scoping review. Frontiers in Neuroscience 2025
Cites 35
- Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. The Lancet Psychiatry May 17, 2016
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study Journal of Psychopharmacology January 13, 2015
and 30 more in the library