Narrating the psychoneuroimmunomodulatory properties of serotonin 5-HT2A receptor psychedelics from a transdiagnostic perspective.
Acta neuropsychiatrica July 25, 2025 Guillaume Thuery, Christopher Sheridan, Patricia Iusan et al. 4 citations
This narrative review synthesizes clinical and preclinical research on how 5-HT2A receptor psychedelics interact with the immune system. The evidence shows these compounds have direct immunomodulatory properties, including downregulation of gene regulators like NF-κB and reduced expression of cytokines such as TNF-α, IL-6, and IL-1β in both the central and peripheral nervous systems. These effects are accompanied by modulation of corticotrophin releasing hormone, adrenocorticotrophic hormone, and cortisol. The immunomodulation occurs through pathways involving serotonin receptors, the Sigma-1 receptor, and the TrkB receptor, as well as indirectly via the HPA axis. The review identifies that modulation of brain glia and glial-neuronal interactions remains to be determined, representing a promising direction for future research on the therapeutic potential of these psychedelics for mental health and brain disorders.