A Nature Neuroscience study found that 5-HT2A receptor, β-arrestin signalling supports sustained antidepressant-like effects of psychedelics in mice.

The study linked LSD’s slow dissociation from 5-HT2A receptors to prolonged β-arrestin signalling and antidepressant-like outcomes in mice. Repeated low doses achieved receptor occupancy comparable to a single high dose while limiting peak levels and Gq/Ca2+ side effects, and researchers designed 5-HT2A receptor, β-arrestin-biased agonists to investigate the pathway.