This article reviews the current clinical evidence for psilocybin and ayahuasca as therapeutic agents, examining data from over 134 registered clinical trials and key publications in the New England Journal of Medicine, JAMA, JAMA Psychiatry, and Nature Neuroscience. The review addresses four dimensions: (1) the state of clinical evidence for psilocybin and ayahuasca in major depression and treatment-resistant depression, including landmark trials by Goodwin et al. (2022), Davis et al. (2021), Raison et al. (2023), and Palhano-Fontes et al. (2019); (2) neurobiological mechanisms underlying therapeutic effects, particularly psychedelic-induced neuroplasticity via BDNF receptor TrkB binding (Moliner et al., 2023) and DMT-regulated adult neurogenesis (Morales-García et al., 2020); (3) the safety profile based on systematic review evidence (Freitas et al., 2025) and established safety guidelines (Johnson, Richards and (4) ethical and cultural considerations for professional practice involving plant-based psychedelic compounds. The article argues that the three-phase model (preparation, experience, integration) documented in leading clinical trials constitutes the minimum professional standard for responsible ceremonial medicine practice. Written from the perspective of a licensed clinical psychologist and certified Psychedelic Assisted Therapist practicing in Costa Rica.
Espinoza Patricio (Fri,) studied this question.
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