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

Psychedelic therapy, combining psychedelic drugs with psychological support, shows promise for treating disorders marked by rigid and unhealthy patterns of emotion, thought, and behavior, including depression, treatment-resistant depression, addiction, and potentially anxiety, OCD, PTSD, and eating disorders. This review examines preclinical and clinical evidence through the Research Domain Criteria (RDoC) framework, mapping the drugs' effects across molecular, cellular, and network levels to RDoC constructs like negative and positive valence, arousal, social processing, cognition, and sensorimotor systems. The goal is to clarify the specific clinical dimensions psychedelics affect and their underlying neurobiology, aiming toward a mechanistic understanding and personalized psychedelic therapy.

Study at a glance

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.