Above the threshold, beyond the trip: the role of the 5-HT2A receptor in psychedelic-induced neuroplasticity and antidepressant effects
Molecular Psychiatry August 23, 2025 Adam J. Drewko, Ron L. P. Habets, Tibor M. Brunt 4 citations
Serotonergic psychedelics like psilocybin and LSD show promise for treatment-resistant depression by rapidly inducing neuroplasticity, but the molecular mechanisms are debated. This narrative review examines evidence on whether the serotonin 5-HT2A receptor, which mediates hallucinogenic effects, is also required for neuroplasticity. It covers how decreased neuroplasticity relates to depression, how psychedelics promote dendrito-, spino-, and synaptogenesis, and whether these effects are regionally selective. The review critically assesses conflicting studies on the necessity of 5-HT2A signaling for neuroplastic effects and presents a model of the molecular mechanisms involved.