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

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.

Models of Psychedelic-Assisted Psychotherapy: A Contemporary Assessment and an Introduction to EMBARK, a Transdiagnostic, Trans-Drug Model

“…Generally, the limitations of EBT-inclusive approaches stem from their introduction of potentially deleterious constraints into how therapeutic benefit is conceptualized in PAP treatment. Therapeutic outcomes in PAP are likely to result from a participant’s engagement with many facets of themselves and their illness during treatment ( Kelly et al, 2021 ; Thal et al, 2021 ; Miceli McMillan and Jordens, 2022 ). Medicine sessions can foster a broad range of experiences that inspire participants to make beneficial meaning of their treatment in an equally broad range of ways that include spiritual, existential, emotional, relational, cognitive, or embodied dimensions ( Masters and Houston, 1966 ; Belser et al, 2017 ; Watts et al, 2017 ; Malone et al, 2018 ; Nielson et al, 2018 ; Michael et al, 2021 ).…”

“…This inattention may reflect the ongoing effort to characterize PAP within the institutional bounds of Western psychiatry and psychology, which attend more exclusively to cognitive and neural phenomena. As such, beneficial outcomes of PAP treatment have been conceptualized in neuropsychological terms that omit participants’ experiences of embodiment ( Kelly et al, 2021 ; Thal et al, 2021 ), such as the “reset” of a maladaptive neural status quo ( Carhart-Harris et al, 2017 ; Carhart-Harris and Friston, 2019 ), increased psychological flexibility ( Watts and Luoma, 2020 ; Agin-Liebes et al, 2022 ), cognitive reappraisal ( Agin-Liebes et al, 2022 ), altered neural responses to affect ( Barrett et al, 2020 ), or increased neuronal and mental plasticity ( Kočárová et al, 2021 ). This centering of the brain-mind may seem unremarkable, given the prevalence of neuropsychological explanations offered by most psychotherapies.…”

A Research Domain Criteria (RDoC)-Guided Dashboard to Review Psilocybin Target Domains: A Systematic Review

“…Accordingly, this review has also shown that psilocybin can benefit multiple domains and constructs, which might further benefit those disparate diagnostic categories with shared dysfunctions across disparate domains and constructs. In support of this view, Kelly and colleagues have also gauged the transdiagnostic potential of psychedelics through the RDoC lens, positing that multidomain effectiveness might explain why these agents seem to be effective in disparate diagnostic categories [ 16 ]. Another recent review has proposed a different hypothesis, which focuses on the psychedelics’ ability to induce neuronal and mental plasticity as a booster to psychotherapy-induced change mechanisms and subsequent transdiagnostic targeting [ 133 ].…”

“…Preliminary results from randomized controlled studies provide evidence that select psychedelics are capable of rapid attenuation of symptoms across some mental disorders (e.g., major depressive disorder, substance use disorder (SUD), anxiety disorders, and trauma-related and stressor-related disorders) [11][12][13][14][15]. The foregoing findings, along with identified molecular, cellular, and circuit targets of select psychedelics (e.g., psilocybin), suggest that their effects are transdiagnostic [16]. Here, we review and synthesize the extant literature evaluating outcomes with psilocybin in accordance with the RDoC framework.…”

Postpartum depression: A role for psychedelics?

“…Early phase clinical trial evidence suggests safety and feasibility of psilocybin given with psychological support in the treatment of depression (Carhart-Harris et al, 2016; Davis et al, 2021), end-of-life distress (Griffiths et al, 2016; Grob et al, 2011; Ross et al, 2016), and substance use disorders (Bogenschutz et al, 2015; Johnson et al, 2014). There is growing evidence for the transdiagnostic applications of psychedelic therapy (Kelly et al, 2021). In this review, we outline the potential therapeutic rationale for serotonergic psychedelics in the treatment of PPD, and highlight safety and pragmatic considerations for the use of psychedelics in the postpartum period.…”