Examining the potential of psilocybin and 5-MeO-DMT as therapeutics for traumatic brain injury.
Zoe Plummer, Josh Allen, Justin Brand, Leah M. Mayo, Sandy R Shultz, Brian R Christie
Progress in Neuro-Psychopharmacology and Biological Psychiatry July 14, 2025 DOI: 10.1016/j.pnpbp.2025.111448 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | 5-MeO-DMT Neuroplasticity Psilocybin DMT |
| Keywords | Concussion Microglia Neuritogenesis Neurotrophic Psychedelic medicine: psychedelic Therapeutic psychedelics Healing compounds Drug therapy Brain damage Neurological repair Brain function restoration Neurorehabilitation Neuroplasticity mechanisms: neuroplasticity Neural regeneration Brain remodeling Cellular repair Inflammation reduction |
| Citations | 4 |
| Key findings | Psilocybin and 5-MeO-DMT may alleviate TBI-related impairments through shared and distinct mechanistic pathways involving neuroplasticity, anti-inflammatory, and neuroprotective effects. |
Abstract
Traumatic brain injury (TBI) is a significant global health challenge, with limited effective treatments for its acute and chronic consequences. TBI is characterized by neuroinflammation, oxidative stress, impaired neuroplasticity, imbalances in neurotransmission, and cell death - factors that contribute to the development of neurological and psychiatric disorders. Emerging evidence suggests that serotonergic psychedelics psilocybin and 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) may hold promise as treatments for TBI. These compounds promote neuroplasticity, exert anti-inflammatory and neuroprotective effects, and have shown efficacy in treating psychiatric conditions that share pathophysiological features with TBI. 5-HT1A and 5-HT2A receptors are implicated in their effects, but psilocybin also targets neurotrophic TrkB receptors, whereas 5-MeO-DMT targets sigma-1 receptors, known to have neuroprotective properties. This review integrates current preclinical and clinical research, highlighting both the shared and distinct mechanistic pathways through which psilocybin and 5-MeO-DMT may alleviate TBI-related impairments, such as cognitive and affective dysfunction and neuroinflammation. Additionally, the safety profiles, dosing paradigms, and clinical challenges of these psychedelics are critically examined. By bridging insights from psychedelic science and neurotrauma research, this review underscores the innovative potential of psilocybin and 5-MeO-DMT as adjunctive treatments for TBI, paving the way for novel interventions in neurorehabilitation.
Comparable studies
Other narrative reviews on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Neuropharmacology of N,N-dimethyltryptamine | 2016 | Review | |
| N, N-Dimethyltryptamine (DMT), an Endogenous Hallucinogen: Past, Present, and Future Research to Determine Its Role and Function Humans and animals (general) | 2018 | Review | |
| Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Humans (pharmacokinetics) | 2010 | Review | |
| Dark Classics in Chemical Neuroscience:N,N-Dimethyltryptamine (DMT) | 2018 | Review | |
| A possibly sigma-1 receptor mediated role of dimethyltryptamine in tissue protection, regeneration, and immunity. | 2013 | Review |
Citations in the library
Cited by 2
Cites 76
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- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
and 71 more in the library