This review of 54 clinical studies found that psilocybin therapy works best when the experience feels deeply meaningful, often described as a “mystical-type” experience involving insight, emotional release, or a sense of connection. Higher psilocybin doses were consistently linked to stronger and longer-lasting improvements across conditions like depression, addiction, anxiety, and end-of-life distress, while age, sex, or education level mattered far less. Brain imaging showed changes in emotion-related areas like the amygdala and prefrontal cortex, helping explain why people feel less stuck in fear or negative thought loops after treatment.