Psilocybin may support recovery after traumatic brain injury
By Myla Hightower. This article was initially published in the 10/9/25 edition of our Concussion Update newsletter; please consider subscribing.
A narrative review in Brain Sciences evaluated 29 studies and found evidence that psilocybin could play a role in recovery after traumatic brain injury (TBI). Lead author Charles Palmer et al. explain that their review found that psilocybin, a natural compound found in Psilocybe mushrooms, reduced numerous pro-inflammatory markers and increased expression of brain-derived neurotrophic factor (BDNF), which influences neuroplasticity. Additionally, psilocybin activates serotonin 5-HT2A receptors, influencing mood-related dopamine pathways and the hypothalamic–pituitary–adrenal axis (the body’s primary hormonal stress response system). Because TBI often disrupts these systems, psilocybin’s effects may help improve recovery by reducing inflammation, promoting neuroplasticity, encouraging the growth of new synapses, and alleviating associated mood disorders.
For those with mood disorders, taking psilocybin may improve mood and reduce depression, anxiety, and PTSD symptoms common after TBI. Additionally, psilocybin does not appear to raise seizure risk, which is a significant safety concern in brain injury care. Still, the evidence remains preliminary. Most of the findings analyzed in this narrative review are from animal models or clinical trials that did not focus on patients with TBI; no randomized clinical trials have directly tested psilocybin in this population. The authors call for well-designed studies to confirm safety, identify effective dosing, and explore how psilocybin could be combined with rehabilitation strategies. Nevertheless, the paper concludes that psilocybin, used alongside existing therapies, “has the potential to maximize TBI recovery.”
Reporting in Marijuana Moment, journalist Ben Adlin emphasized this conclusion while also noting the authors’ caution towards potential risks, such as challenging psychological experiences. The review stresses that treatment protocols should include careful screening, preparatory sessions, and controlled settings, which are considered essential for safety in psychedelic therapy. The authors also highlight legal barriers: psilocybin remains a Schedule I substance in the U.S., restricting research and slowing progress towards clinical trials. Even so, decriminalization initiatives and rising federal interest, particularly in veteran care, are creating momentum for future trials. Oregon and Colorado have legalized “psilocybin for medically supervised use,” and nine states have decriminalized psilocybin.
