Both show evidence of benefit, but at different levels of certainty. Psilocybin has received FDA Breakthrough Therapy designation for treatment-resistant depression and major depressive disorder and has over 134 registered clinical trials as of 2023 (Gukasyan and Nayak, 2023; COMPASS Pathways, 2018). For ayahuasca, the strongest evidence comes from the 2019 Palhano-Fontes RCT, with a single dose producing large reductions in depression scores in treatment-resistant patients, with a Cohen’s d of 0.98 at day 7, though the trial involved only 29 participants. Psilocybin currently has the more developed research infrastructure for depression. Ayahuasca’s evidence is promising but not yet at the same clinical maturity.
