Serotonergic Psychedelics as a Potential Therapeutic Strategy for Anxiety, A Systematic Review
PsyArXiv May 24, 2026 Naja Bralic, Elena Bragagnolo, Mikael Palner preprint
Serotonergic psychedelics such as psilocybin and DOI show anxiolytic-like effects in animal models, though anxiogenic and null results also occur, indicating context-dependent outcomes influenced by dosage, administration pattern, biological variables, and experimental conditions. A systematic review of 18 preclinical studies found generally acceptable predictive and face validity in behavioral tests, but construct validity had limitations and inconsistencies in experimental conditions need standardization. Psilocybin produced consistent anxiolytic-like effects, possibly through 5-HT2A receptor agonism, suggesting therapeutic potential for anxiety. Future research should focus on mechanisms, sex-specific effects, and improved behavioral test combinations.