Depressive disorders are a leading cause of disability worldwide, with many patients experiencing insufficient response or limiting side effects from conventional antidepressants, particularly those with treatment-resistant depression. Psilocybin has emerged as a promising therapeutic alternative, showing rapid, robust, and potentially lasting antidepressant effects when administered in a controlled clinical setting with psychological support. This systematic review, following PRISMA guidelines and searching PubMed for studies from 2015 to 2025, included ten studies (randomized controlled trials and observational studies) in adults aged 18 and older.
Psychedelics such as MDMA and psilocybin may help treat post-traumatic stress disorder (PTSD) by promoting neuroplasticity and facilitating the reconsolidation of traumatic memories. MDMA reduces amygdala response and increases feelings of safety during psychotherapy, allowing patients to reprocess traumatic memories. Psilocybin can loosen rigid thought patterns, supporting emotional reframing. These substances modulate serotonin 5-HT2A receptors, enhancing neural connectivity and reorganization of memory and emotion circuits. Safety requires strict protocols, careful screening, and professional supervision due to risks like acute anxiety and cardiovascular instability. When used in controlled, therapy-integrated settings, psychedelics represent a promising avenue for PTSD treatment, though clinical adoption depends on regulation, training, and further long-term efficacy studies.