Major Depressive Disorder (MDD)Depressive DisordersPTSDPsilocybinMDMA

Psilocybin and MDMA for the treatment of trauma-related psychopathology

This review (2021) investigates the therapeutic rationale behind the use of psilocybin and MDMA in the treatment of PTSD and depression. Both compounds and the possible treatment modalities (the combination with talk therapy) are discussed. A combination of first MDMA-assisted therapy, followed by psilocybin-assisted therapy is also presented.

Authors

  • James Rucker
  • Nadav Liam Modlin

Published

International Review of Psychiatry
meta Study

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.

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Research Summary of 'Psilocybin and MDMA for the treatment of trauma-related psychopathology'

Introduction

Bird and colleagues frame the paper within a renewed interest in drug-assisted psychotherapy for trauma-related mental disorders. Trauma exposure is common and contributes substantially to psychiatric morbidity; Post-Traumatic Stress Disorder (PTSD) requires a trauma antecedent but trauma history also strongly increases risk for major depressive disorder (MDD) and other conditions. The authors note important clinical overlap between PTSD and MDD and argue that overlapping symptomatology and neurobiology complicate nosology and treatment choices. Against this background, classical psychedelics (notably psilocybin) and MDMA have re-emerged in clinical research after decades of legal restriction, and both have received FDA “breakthrough therapy” designations for, respectively, resistant MDD (psilocybin) and PTSD (MDMA). The review sets out to synthesise evidence relevant to using psilocybin- and MDMA-assisted psychotherapy in trauma-related MDD and PTSD. The authors examine clinical and preclinical data on safety, efficacy signals, and putative mechanisms—neurobiological, psychological and social—that might explain therapeutic effects. They also raise a pragmatic question considered later in the paper: whether sequencing MDMA and psilocybin (one before the other) could be advantageous for different trauma-related presentations.

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Study Details

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