This review examines how psychedelic substances like psilocybin and MDMA, when combined with professional psychotherapy, show promise in treating difficult-to-treat mental health conditions including depression, PTSD, and anxiety. While early research suggests these substances could help in cases where conventional treatments have failed, the evidence is still preliminary and limited by small study sizes. Psychedelics appear to work by changing how the brain processes information and memories, though much more rigorous research is needed before they can be considered standard treatments.