Major Depressive Disorder (MDD)Depressive DisordersAnxiety DisordersNeuroimaging & Brain MeasuresMicrodosingMedicinal Chemistry & Drug Development

Psychedelic Medicines in Major Depression: Progress and Future Challenges

This book chapter (2021) describes the current research on psychedelics for depression (MDD), the clinical trials as well as the neurobiological mechanisms are described. The chapter end with a description of future challenges.

Authors

  • Jamie Hallak
  • Rafael dos Santos
  • Gonzalo Ona

Published

Advances in Experimental Medicine and Biology
meta Study

Abstract

The volume of research on the therapeutic use of psychedelic drugs has been increasing during the last decades. Partly because of the need of innovative treatments in psychiatry, several studies have assessed the safety and efficacy of drugs like psilocybin or ayahuasca for a wide range of mental disorders, including major depression. The first section of this chapter will offer an introduction to psychedelic research, including a brief historical overview and discussions about appropriate terminology. In the second section, the recently published clinical trials in which psychedelic drugs were administered to patients will be analysed in detail. Then, in the third section, the main neurobiological mechanisms of these drugs will be described, noting that while some of these mechanisms could be potentially associated with their therapeutic properties, they are commonly used as adjuvants in psychotherapeutic processes. The last section suggests future challenges for this groundbreaking field of research and therapy.

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Research Summary of 'Psychedelic Medicines in Major Depression: Progress and Future Challenges'

Introduction

Psychedelic compounds — including plant preparations, fungi and synthetic molecules — produce profound alterations in consciousness and have millennia‑long ritual and medicinal uses in many indigenous cultures. The terminology and conceptual framing of these substances remain contested: early Western research distinguished psycholytic (low‑dose, therapy‑assisting) and psychedelic (high‑dose, spiritual experience) paradigms, and contemporary work generally focuses on serotonergic psychedelics (LSD, psilocybin, DMT/ayahuasca) that act largely at 5‑HT2A receptors. Renewed scientific interest since the 1990s has reflected both advances in neuropharmacology and the perceived need for novel psychiatric treatments. Bouso and colleagues set out to review recent clinical trials that have tested psychedelic medicines for anxiety and depressive disorders, to summarise proposed neurobiological mechanisms that might underlie antidepressant effects, and to outline the main challenges facing clinical development and implementation. The chapter is a narrative synthesis rather than a systematic review and aims to integrate clinical findings, neuroimaging and molecular data with practical and regulatory considerations for translating psychedelic‑assisted therapies into clinical practice.

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Study Details

References (35)

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