From molecules to meaning: unpacking the antidepressant mechanisms of psychedelic drugs.
Expert review of clinical pharmacology June 11, 2025 Victor Pablo Acero, Taylor A Flatt, Peter M Gooch et al.
Psychedelic compounds can produce rapid and lasting depression symptom reduction after one or two administrations paired with psychotherapy, unlike traditional antidepressants. Current evidence on their antidepressant mechanisms is fragmented across biological, psychological, social, and spiritual domains. This review identifies key mechanisms in each domain, comparing them with those of conventional antidepressants to highlight overlaps and differences. The authors caution that focusing too narrowly on discrete pathways may limit progress, as psychedelics likely work through complex, interwoven processes. Future research should examine how suprapharmacological factors—set, setting, therapy modality, and integration—shape outcomes, moving beyond frameworks used for standard antidepressants.