Psilocybin and MDMA for the treatment of trauma-related psychopathology

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.

Study at a glance

Abstract

This review examines the role of trauma in psychiatric morbidity and analogous psychoneurobiological changes. Trauma is a necessary criterion for Post-Traumatic Stress Disorder (PTSD), however, trauma history is highly correlated with a variety of psychiatric conditions. Some evidence suggests that Major Depressive Disorder (MDD) is the most common psychiatric condition that arises following trauma. Approximately 50% of PTSD cases present with co-morbid MDD. Overlapping symptomatology and neurobiology between these conditions underlie the debate over whether these phenomena result from problematic nosology or whether comorbid MDD + PTSD is a distinct phenotype of trauma-related psychopathology. Regardless, similar treatment approaches have been employed historically, with varying success. The drug-assisted psychotherapy treatment model, which combines pharmacological and psychotherapeutic approaches, is currently being trialled as a novel treatment approach in psychiatry. Both psilocybin- and 3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy have received Food and Drug Administration 'breakthrough therapy' designation for the treatment of resistant MDD and PTSD, respectively. This paper reviews the therapeutic rationale of both psilocybin and MDMA for treating both trauma-related MDD and PTSD.