Over a five-year follow-up period, psilocybin-assisted therapy produced significant and sustained reductions in depression for people with major depressive disorder. Among the 18 participants who completed the study, 67% remained in remission for at least five years after treatment. Anxiety and functional impairment also improved. Qualitative interviews revealed lasting positive changes in mindset, emotional health, and relationships, including enhanced empathy, self-acceptance, and improved interpersonal relationships. No severe adverse events were reported. These findings support the long-term efficacy and safety of psilocybin-assisted therapy for reducing depressive symptoms and improving mental health.
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.