Psilocybin is a psychedelic agent found in nature. Ketamine is a substance designed in laboratories over sixty years ago. Both have been the subject of debate and controversy because of their use as recreational drugs and the potential health risks that can result from their uncontrolled administration. However, both can also be used as therapeutic agents. In the case of ketamine, in addition to its long history as an anesthetic agent, a derivative (esketamine) has recently been developed and approved for resistant depression. In the case of psilocybin, a growing number of clinical trials support its potential to treat this same condition. Previous studies show promising results for both agents. For instance, a recent systematic review exploring the effectiveness of both stated that both had demonstrated effectiveness in reducing depressive symptoms, characterized by a rapidity of effect that manifested itself shortly after intake and was maintained over time (Psiuk et al., 2022). Our own experience in a mental health outpatient clinic of ketamine for the management of depression and suicidal ideation shows promising results in this field. In the case of psilocybin, the clinical trial conducted in our hospital aims to find the appropriate dose of this substance which, combined with specific psychotherapy, is showing positive results in patients with resistant depression and suicidal ideation.