Psychedelics for acquired brain injury: a review of molecular mechanisms and therapeutic potential
This review (2023) explores the potential of psychedelics as a therapeutic intervention for acquired brain injury (ABI), such as traumatic brain injury (TBI) and stroke. It highlights the challenge in managing ABI despite medical advancements and suggests psychedelics may improve neurobehavioral outcomes due to their impact on serotonin receptors, sigma-1 receptors, and neurotrophic signalling.
Authors
- Allen, J.
- Dames, S.
- Foldi, C. J.
Published
Abstract
Acquired brain injury (ABI), such as traumatic brain injury and stroke, is a leading cause of disability worldwide, resulting in debilitating acute and chronic symptoms, as well as an increased risk of developing neurological and neurodegenerative disorders. These symptoms can stem from various neurophysiological insults, including neuroinflammation, oxidative stress, imbalances in neurotransmission, and impaired neuroplasticity. Despite advancements in medical technology and treatment interventions, managing ABI remains a significant challenge. Emerging evidence suggests that psychedelics may rapidly improve neurobehavioral outcomes in patients with various disorders that share physiological similarities with ABI. However, research specifically focussed on psychedelics for ABI is limited. This narrative literature review explores the neurochemical properties of psychedelics as a therapeutic intervention for ABI, with a focus on serotonin receptors, sigma-1 receptors, and neurotrophic signalling associated with neuroprotection, neuroplasticity, and neuroinflammation. The promotion of neuronal growth, cell survival, and anti-inflammatory properties exhibited by psychedelics strongly supports their potential benefit in managing ABI. Further research and translational efforts are required to elucidate their therapeutic mechanisms of action and to evaluate their effectiveness in treating the acute and chronic phases of ABI.
Research Summary of 'Psychedelics for acquired brain injury: a review of molecular mechanisms and therapeutic potential'
Introduction
Allen and colleagues situate this review within the renewed scientific interest in psychedelic compounds after decades of restricted research. They note that classical psychedelics (for example psilocybin, DMT, LSD) and some non-classical agents (for example ibogaine, ketamine) act on diverse receptor systems but are most commonly associated with agonism at serotonin (5-HT) receptors, especially 5-HT2A. The authors highlight that psychedelics have been reported to produce rapid and, in some cases, long-lasting therapeutic effects across a range of psychiatric and behavioural disorders, and that these effects are thought to involve changes in neuroplasticity, neurotrophic signalling, and immune modulation. At the same time, the field lacks focused investigation of psychedelics in acquired brain injury (ABI), a heterogeneous group of conditions (including traumatic brain injury and stroke) that cause persistent cognitive, emotional and neurological deficits driven by processes such as excitotoxicity, oxidative stress, apoptosis, and chronic neuroinflammation. This paper therefore aims to review the preclinical and clinical literature relevant to using psychedelics in the context of ABI, emphasising molecular and cellular pathways that could underlie neuroprotection, neuroregeneration and anti-inflammatory effects. The authors state their focus on serotonin receptors, sigma-1 receptors, and neurotrophic signalling (notably BDNF–TrkB pathways), and they set out to assess whether the pharmacology of psychedelics provides a mechanistic rationale for acute and/or chronic interventions after ABI. The review is presented as a narrative literature synthesis intended to inform future translational and clinical work in this area.
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Study Details
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Allen, J., Dames, S. S., Foldi, C. J., & Shultz, S. R. (2024). Psychedelics for acquired brain injury: a review of molecular mechanisms and therapeutic potential. Molecular Psychiatry, 29(3), 671-685. https://doi.org/10.1038/s41380-023-02360-0
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