Traumatic brain injury (TBI) can have lasting effects on cognitive functioning, emotional wellbeing and everyday life. Difficulties with memory, attention, fatigue, anxiety and depression can persist long after the initial injury.
Although neurorehabilitation can support recovery and adaptation, effective treatments for the longer-term neurological and psychological consequences of TBI remain limited. This has encouraged researchers to investigate alternative therapeutic approaches, including the potential role of psychedelic compounds such as psilocybin.
Psilocybin, the naturally occurring psychedelic compound found in certain mushroom species, has attracted scientific interest for its effects on neuroplasticity, brain connectivity and mental health. A narrative review by Palmer et al. (2025) explored its potential application to TBI, highlighting three possible therapeutic pathways: reducing neuroinflammation, promoting neuroplasticity and addressing psychological symptoms that commonly accompany brain injury.
Interest is also emerging from people living with TBI themselves. VanderZwaag et al. (2026) analysed responses from a global psychedelic survey, identifying 145 individuals who reported using psychedelics to manage TBI-related symptoms. Psilocybin was the most reported psychedelic used across their lifetimes, with 74.5% reporting previous use, while 26.9% selected it as the substance they perceived to be most effective.
These findings suggest that some individuals are already exploring psychedelics to manage the consequences of brain injury.
As research develops, an important question is emerging: could psilocybin offer benefits beyond psychological wellbeing, potentially influencing some of the biological processes involved in brain injury recovery?
Following TBI, the brain can undergo a series of secondary changes involving inflammation, disrupted communication between neural networks and alterations in neuroplasticity. These processes may contribute to persistent cognitive, emotional and behavioural difficulties.
Psilocybin primarily acts through the serotonin 5-HT2A receptor and has been associated with changes in neural signalling and plasticity. Palmer et al. (2025) proposed that these effects could have therapeutic relevance following TBI, although much of the supporting evidence at the time came from research outside brain injury populations.
Allen et al. (2026) examined the effects of a single psilocybin administration in rats one year after sustaining a TBI. The researchers reported improvements in injury-associated behavioural deficits, alongside restoration of altered 5-HT2A receptor binding and reduced microglial density in the prefrontal cortex. Microglia are immune cells involved in the brain's inflammatory response, making these findings relevant to understanding the potential relationship between psilocybin and neuroinflammatory processes.
In simpler terms, psilocybin appeared to improve certain behaviours affected by brain injury, while also influencing brain signalling and reducing markers associated with inflammation.
In another study, Brengel et al. (2026) investigated psilocybin in female rats exposed to repetitive mild head injuries. The researchers identified several notable biological changes, including reduced measures of brain oedema, altered functional connectivity and vascular reactivity, and increased levels of brain-derived neurotrophic factor (BDNF).
Of particular interest is the increase in BDNF, a protein involved in the brain's ability to form and strengthen neural connections, suggesting a potential pathway through which psilocybin could support recovery following injury.
Together, these studies provide early experimental support for some of the mechanisms proposed by Palmer et al. (2025). They suggest that psilocybin may influence processes associated with persistent brain injury.
While these findings provide promising insights into psilocybin's potential neurorestorative properties, both studies were conducted in animals. The question, therefore, is whether similar benefits might be observed in people living with TBI.
From Preclinical Research to Human Evidence
Although preclinical findings are encouraging, research investigating psilocybin in people with brain injuries remains at an early stage.
One case report by Lawrence et al. (2025) described a 22-year-old collegiate athlete experiencing persistent symptoms following concussion. Despite receiving multidisciplinary care, the athlete continued to experience headaches, sensory sensitivity and cognitive difficulties.
Approximately six weeks after injury, he independently used three low doses of psilocybin-containing mushrooms over several days. He subsequently reported improvements in headache, sensitivity to light and noise, concentration and overall functioning. His recorded symptom severity score decreased from 25 to 11, while improvements in activity tolerance supported his return towards normal sporting and academic participation.
Although these observations are interesting, the report describes a single individual. The improvements cannot be attributed confidently to psilocybin, particularly given the potential for natural recovery following concussion.
However, more exciting findings have emerged from a larger observational study by Blest-Hopley et al. (2025), which examined psychological and neurophysiological changes in military veterans reporting a history of TBI following participation in a psilocybin retreat.
The study recruited 21 veterans and incorporated psychological assessments alongside electroencephalography (EEG), which measures electrical activity in the brain. Among participants with available follow-up data, researchers reported reductions in symptoms of post-traumatic stress disorder (50%), depression (65%) and anxiety (28%) four weeks after the retreat.
The researchers also identified changes in EEG activity, including measures of brainwave power and connectivity. These findings suggest that the retreat experience was associated with both psychological and measurable neurophysiological changes.
Beyond clinical assessments and neurophysiological measurements, qualitative research offers another perspective by exploring how people living with brain injuries experience psychedelics and the changes they associate with their use.
In my own qualitative study (Reed, 2026), I interviewed five individuals living with traumatic brain injury who had used psychedelics. Although the research explored several psychedelic substances, psilocybin was among the most reported. Three central themes emerged: trauma relief and mood stabilisation; a perceived post-dose cognitive ‘lift’; and insight, acceptance and self-compassion.
Participants described reductions in anxiety, emotional distress and trauma-related symptoms following psychedelic experiences, including those involving psilocybin. One participant reported a noticeable reduction in anxiety following a psilocybin session, describing a sense of emotional relief that contrasted with their usual post-injury difficulties. These experiences offer a personal perspective on the psychological changes also observed in the study by Blest-Hopley et al. (2025).
Another notable finding was what participants described as a post-dose cognitive ‘lift’, characterised by improvements in memory, mental clarity and coordination. These changes were most frequently associated with larger psilocybin doses, with some participants reporting effects lasting days, weeks or even months.
Participants also described developing a greater understanding of how their injuries had affected their emotions, behaviour and sense of identity. Some reported feeling more accepting of their circumstances, while others described reconnecting with aspects of themselves they felt had been lost following injury. These accounts suggest that, alongside perceived changes in symptoms and cognition, psilocybin could also influence how individuals understand and relate to their brain injuries.
The Potential Role of Psilocybin in Neurorehabilitation
Neurorehabilitation encompasses a range of neurological conditions, including traumatic and non-traumatic acquired brain injuries, such as stroke and hypoxic brain injury. Despite their different causes, many individuals experience overlapping challenges involving cognition, emotional regulation and psychological adjustment.
In my own research (Reed, 2026), I proposed that psychedelic interventions could potentially support neurorehabilitation across three interconnected areas: reducing emotional and trauma-related distress, improving aspects of cognitive functioning, and supporting acceptance and adjustment following injury. Of particular interest is whether psilocybin's proposed effects on neuroplasticity, alongside its psychological effects, could complement existing rehabilitation approaches. For example, could a period of improved cognitive flexibility or emotional wellbeing create opportunities for greater engagement in cognitive rehabilitation, psychological therapy or other structured interventions?
Ultimately, the question is not simply whether psilocybin can improve individual symptoms following brain injury, but whether its potential biological and psychological effects could eventually be meaningfully integrated into the wider neurorehabilitation process.
What Comes Next?
An important next step is already underway at Monash University in Australia, where researchers have launched a clinical trial investigating psilocybin-assisted therapy for persistent post-concussion symptoms. Beginning in 2026, the three-year study will examine whether psilocybin can improve outcomes in individuals experiencing symptoms for at least six months following concussion.
Unlike the observational studies discussed earlier, this trial will use a randomised, double-blind, active placebo-controlled design. Researchers will assess clinical outcomes alongside blood and neuroimaging biomarkers, helping to investigate both the potential therapeutic benefits and underlying biological effects of psilocybin.
Studies such as this represent an important step towards establishing whether the promising findings emerging from preclinical research and early human observations can translate into meaningful improvements for people living with brain injuries.
Although concussion represents only one part of the wider spectrum of brain injuries, this trial marks an important step towards more rigorous clinical investigation. Its findings could help inform future research involving individuals with more severe TBI, as well as other forms of acquired brain injury, such as stroke and hypoxic brain injury. Ultimately, understanding whether psilocybin can produce meaningful and measurable improvements following concussion may provide a foundation for exploring its potential applications across the broader field of neurorehabilitation.
References
Allen, J. et al. (2026). ‘Psilocybin restores behaviour and 5-HT2A signalling while reducing microglial density after chronic traumatic brain injury in rats’. Cell Reports Medicine, 7(7), 102867.
Blest-Hopley, G. et al. (2025). ‘Improved mental health outcomes and normalised spontaneous EEG activity in veterans reporting a history of traumatic brain injuries following participation in a psilocybin retreat’. Frontiers in Psychiatry.
Brengel, E.K. et al. (2026). ‘Psilocybin as a treatment for repetitive mild head injury: evidence from neuroradiology and molecular biology’. Communications Biology.
Lawrence, D.W. et al. (2025). ‘Psilocybin use in an intercollegiate athlete with persisting symptoms after concussion: a case report’. Psychoactives, 4(3), 22.
Palmer, C., Ferber, A.T. and Greenwald, B.D. (2025). ‘The potential role of psilocybin in traumatic brain injury recovery: a narrative review’. Brain Sciences, 15(6), 572.
Reed, O. (2026). ‘Exploring the potential of psychedelics in brain injury recovery: a thematic analysis of participant narratives’. Frontiers in Neurology.
VanderZwaag, B. et al. (2026). ‘Psychedelics for the management of symptoms of traumatic brain injury: findings from the global psychedelic survey’. Progress in Neuro-Psychopharmacology & Biological Psychiatry.