Psilocybin as a treatment for repetitive mild head injury: evidence from neuroradiology and molecular biology

Repetitive mild head injuries incurred while playing organized sports, during car accidents and falls, or in active military service are a major health problem. These head injuries induce cognitive, motor, and behavioral deficits that can last for months and even years, with an increased risk of dementia, Parkinson’s disease, and chronic traumatic encephalopathy. There is no approved medical treatment for these types of head injuries.

To this end, we tested the therapeutic effects of the naturally occurring psychedelic psilocybin, as it is known to reduce neuroinflammation and enhance neuroplasticity. Using a model of mild repetitive head injury in adult female rats, we provide data indicating that psilocybin can reduce vasogenic edema, restore normal vascular reactivity and alter resting-state functional connectivity, reduce phosphorylated tau buildup, enhance levels of brain-derived neurotrophic factor and its receptor TrkB, and modulate lipid signaling molecules. We thank the National Institute on Drug Abuse, Drug Supply Program, and the Research Triangle Institute for providing the PSI used in these studies.

We also thank the Center for Translational NeuroImaging and Ekam Imaging for financial support. We thank the Institute for Chemical Imaging of Living Systems (RRID:SCR_022681) at Northeastern University for confocal microscopy consultation and instrument support. Boerger Fund of the Delaware Community Foundation.

Fellowships for M.I.A.: NIH-NIGMS R25GM122722 and National Science Foundation 2023004. CIHR (Canadian Institutes of Health Research) project grant to A.A.-V. Canada Graduate Scholarships from NSERC to B.R.

Department of Psychology, Northeastern University, Boston, MA, USA Eric K. Ferris Center for Translational Neuroimaging, Northeastern University, Boston, MA, USA Eric K. Brengel, Bryce Axe, Ashwath N.

Maheswari, Rachel Utama, Noah J. Cavallaro, Anna Brettler, Courtney Sawada, Anna Moore, Shreyas Balaji, Praveen P. Ferris Department of Biological Sciences, Delaware State University, Dover, DE, USA Department of Psychology, Northern Illinois University, DeKalb, IL, USA Department of Psychological & Brain Sciences, Program in Neuroscience, Indiana University, Bloomington, IN, USA Taylor J.