Trauma contributes to many psychiatric conditions beyond PTSD, with major depressive disorder (MDD) being the most common. About half of PTSD cases also have MDD, and their overlapping symptoms and neurobiology raise questions about whether they are distinct disorders or a single trauma-related phenotype. Traditional treatments have had mixed success. Drug-assisted psychotherapy, combining medication with therapy, is emerging as a novel approach. Psilocybin- and MDMA-assisted psychotherapy have received FDA 'breakthrough therapy' designation for resistant MDD and PTSD, respectively. This review examines the rationale for using these substances to treat trauma-related MDD and PTSD.
Setting up a psychedelic study is a long and complex process that presents unique challenges not yet standardized. This review brings together major UK research teams to formalize these considerations, identify ongoing debates, and provide a practical guide for researchers and policymakers. It addresses challenges to existing assumptions about psychiatric prescribing, the placebo effect, and definitions of selfhood. The paper can be read end-to-end or used as a manual with sections for specific needs.