Psychedelics for acquired brain injury: a review of molecular mechanisms and therapeutic potential

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.