A systematic review of 12 studies examined two psychoactive compounds, psilocybin and esketamine, for treating depression. Esketamine, a laboratory-made substance, showed significant reduction in depressive symptoms and suicidal ideation shortly after intake and after one month, compared to baseline and standard antidepressants. Psilocybin, a naturally occurring psychedelic, produced antidepressant effects one day after intake and after 6–7 weeks, with benefits lasting up to 6 or 8 months. One study suggested psilocybin's effects are comparable to and may be superior to escitalopram. Both compounds demonstrated rapid and sustained effects, indicating potential as novel antidepressant agents after addressing limitations.
A systematic review of 14 clinical trials from the last decade found that psychedelic substances, particularly psilocybin, can reduce depressive symptoms as measured by several psychological scales, with effects often lasting months after the last session. One study showed psilocybin has comparable efficacy to escitalopram for treating depression. No serious adverse events were reported. The authors suggest psychedelics hold great potential for depression therapy, pending further research to address current study limitations.