Ayahuasca is an Amazonian psychedelic brew that has been shown to have good results as a potential treatment for major depression. A double-blinded, placebo-controlled trial with treatment-resistant depressive patients and healthy volunteers showed that a single ayahuasca dose induced a significantly larger drop in depressive symptoms than placebo, as well as a stronger clinical response and remission rate. Moreover, ayahuasca induced some improvements in important physiological systems linked to depression like the stress response, systemic inflammation, and neuroplasticity. The understanding of clinical and biological responses to psychedelics with antidepressant potential is useful because it contributes to paving the way for validation of psychedelic therapy.