An overview of psilocybin, LSD, MDMA, and ketamine in revitalizing psychedelic-assisted therapy: Insights, limitations and future directions.
Progress in neuro-psychopharmacology & biological psychiatry July 25, 2025 Kiana Askariyan, Mohammad Taghi Joghataei, Samaneh Dehghan et al. 9 citations
Psychedelic-assisted psychotherapy, using compounds like psilocybin, LSD, MDMA, and ketamine, represents a significant shift in mental health treatment. These agents modulate serotonin receptors and brain network connectivity, with each having distinct pharmacological profiles: psilocybin and LSD share serotonergic pathways but differ in receptor specificity, MDMA offers empathogenic properties, and ketamine provides rapid antidepressant action. Recent FDA breakthrough therapy designations for psilocybin and MDMA signal growing evidence-based acceptance. However, the field faces challenges including methodological limitations, regulatory barriers, and ethical concerns. This narrative review synthesizes historical developments, mechanisms, and clinical outcomes, calling for rigorous research and diverse patient cohorts to integrate psychedelics with psychotherapy effectively.