A meta-analysis of ten studies found that one or two doses of psilocybin produce rapid and sustained antidepressant effects lasting up to six months. Depressive symptoms decreased substantially, with the largest effect at one week (standardized mean difference -1.74) and a still-large effect at six months (-1.12). Higher doses and two sessions were linked to greater improvement. Psilocybin raised systolic blood pressure by 19.00 mmHg and diastolic by 8.66 mmHg, but discontinuation rates and heart rate changes were similar to placebo. The findings suggest psilocybin has favorable cardiovascular safety and acceptability for treating depression.
A systematic review and network meta-analysis of randomized controlled trials compared oral psychedelics (MDMA, LSD, psilocybin, ayahuasca) and escitalopram for depressive symptoms. Placebo responses were lower in psychedelic trials than in antidepressant trials. Only high-dose psilocybin outperformed placebo from antidepressant trials, with a mean difference of 6.45 on the Hamilton depression rating scale. However, when the reference arm shifted from psychedelic-trial placebo to antidepressant-trial placebo, the effect size dropped from large (0.88) to small (0.31). High-dose psilocybin showed a larger relative effect than escitalopram at 10 mg and 20 mg. No intervention caused higher discontinuation or severe adverse events than placebo.