Major Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive DisordersPTSDAnxiety DisordersObsessive-Compulsive Disorder (OCD)Substance Use Disorders (SUD)Eating Disorders

Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective

This review (2021) uses the Research Domain Criteria (RDoC) as a template to analyse the multimodal mechanisms underlying the transdiagnostic therapeutic effects of psychedelic therapy, covering molecular, cellular and network levels. This is the first review to use the RDoC to explore psychedelic therapies and may facilitate a precise-personalized psychedelic therapy paradigm.

Authors

  • John Kelly
  • Veronica O'keane

Published

Frontiers in Psychiatry
meta Study

Abstract

Accumulating clinical evidence shows that psychedelic therapy, by synergistically combining psychopharmacology and psychological support, offers a promising transdiagnostic treatment strategy for a range of disorders with restricted and/or maladaptive habitual patterns of emotion, cognition and behavior, notably, depression (MDD), treatment resistant depression (TRD) and addiction disorders, but perhaps also anxiety disorders, obsessive-compulsive disorder (OCD), Post-Traumatic Stress Disorder (PTSD) and eating disorders. Despite the emergent transdiagnostic evidence, the specific clinical dimensions that psychedelics are efficacious for, and associated underlying neurobiological pathways, remain to be well-characterized. To this end, this review focuses on pre-clinical and clinical evidence of the acute and sustained therapeutic potential of psychedelic therapy in the context of a transdiagnostic dimensional systems framework. Focusing on the Research Domain Criteria (RDoC) as a template, we will describe the multimodal mechanisms underlying the transdiagnostic therapeutic effects of psychedelic therapy, traversing molecular, cellular and network levels. These levels will be mapped to the RDoC constructs of negative and positive valence systems, arousal regulation, social processing, cognitive and sensorimotor systems. In summarizing this literature and framing it transdiagnostically, we hope we can assist the field in moving toward a mechanistic understanding of how psychedelics work for patients and eventually toward a precise-personalized psychedelic therapy paradigm.

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Research Summary of 'Psychedelic Therapy's Transdiagnostic Effects: A Research Domain Criteria (RDoC) Perspective'

Introduction

Dursun and colleagues situate this paper within the rapid expansion of translational psychedelic science and note accumulating clinical signals that psychedelic-assisted interventions, combining pharmacology and psychological support, may produce clinically meaningful benefits across multiple diagnostic categories. The authors foreground a central challenge: while early clinical and preclinical studies suggest antidepressant, anxiolytic and anti-addictive effects, the precise clinical dimensions and underlying neurobiological pathways responsible for those transdiagnostic effects remain poorly characterised. They highlight the primary pharmacological locus for classical psychedelics as 5-HT2A receptor activation, particularly on cortical layer 5 pyramidal cells, and introduce the REBUS (Relaxed Beliefs under Psychedelics and the Anarchic Brain) model as a contemporary explanatory framework that proposes a relaxation of higher-order priors and increased bottom-up information flow during the psychedelic state. The review sets out to map preclinical and clinical evidence onto the National Institute of Mental Health's Research Domain Criteria (RDoC) dimensional framework, examining how psychedelics modulate negative and positive valence systems, arousal/regulatory processes, social processing, cognitive systems and sensorimotor domains across multiple levels of analysis (genes to behaviour). The authors aim to synthesise multimodal mechanisms (molecular, cellular, network) in order to advance a systems-based, precise-personalised paradigm for psychedelic therapy and to guide future mechanistic and clinical work.

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References (192)

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