RPD108 - Demoralization in Psilocybin-Assisted Therapy for Advanced Cancer: An Exploratory Network Analysis

Key Message : Exploratory network analyses of baseline data from an NIH-funded randomized controlled trial of psilocybin-assisted psychotherapy (PAP) identified demoralization as a central distress symptom. These findings suggest that PAP-based interventions targeting demoralization may yield downstream reductions in other distress symptoms, highlighting the need for further research into meaning-centered psychotherapies in PAP.

Abstract: Emerging evidence from psilocybin-assisted psychotherapy (PAP) trials suggests that this intervention can alleviate psychological distress and enhance well-being among individuals with advanced cancer (1). Network approaches offer insights beyond traditional latent variable models by conceptualizing distress as a system of mutually reinforcing symptoms (2). Minimal research has utilized network analysis to examine how distress manifests within the context of PAP. Identifying central symptoms in cancer-related distress networks may inform treatment targets and optimize PAP delivery.
An exploratory network analysis was conducted on baseline data from an NIH-funded, multi-site randomized controlled trial investigating PAP for psychiatric and existential distress in advanced cancer. Baseline variables included demoralization (DS-II), anxiety (HADS-A), depression (HADS-D), desire for hastened death (SAHD), death anxiety (DADDS), and spiritual well-being (FACIT-Sp-12). Networks were estimated using EBICglasso (γ = 0.5) with z-scored variables in R (version 2025.09.0). Stability was assessed via 1,000 nonparametric bootstraps.
The sample (N = 31) was predominantly female (58%), White/non-Hispanic (87%), and heterosexual (87%), with a mean age of 53.7 years (SD = 11.6). Study participants reported high demoralization (M = 12.5, SD = 7.4). The strongest edges were between anxiety and demoralization (wᵢⱼ = 0.53, 95% CI [0.22, 0.69]) and demoralization and desire for hastened death (wᵢⱼ = 0.52, 95% CI [0.00, 0.68]). Demoralization emerged as the most central node (strength = 1.75, betweenness = 10), suggesting it is a core feature of distress among individuals seeking PAP.
Interventions addressing demoralization may have downstream effects on other distress symptoms. These findings support the rationale for exploring meaning-centered psychotherapies (e.g., logotherapy) within PAP. Although some edge confidence intervals included zero, indicating limited precision, future studies should examine how targeting demoralization may alleviate distress and how facets of the acute psychedelic experience (e.g., mystical experiences, emotional breakthroughs, self-compassion) interact with distress networks within this psychopharmacotherapeutic paradigm.

References: 1. Bader, H., Farraj, H., Maghnam, J., & Abu Omar, Y. (2024). Investigating the therapeutic efficacy of psilocybin in advanced cancer patients: A comprehensive review and meta-analysis. World journal of clinical oncology, 15(7), 908–919. https://doi.org/10.5306/wjco.v15.i7.908

2. Borsboom, D., & Cramer, A. O. (2013). Network analysis: an integrative approach to the structure of psychopathology. Annual review of clinical psychology, 9, 91–121. https://doi.org/10.1146/annurev-clinpsy-050212-185608