Impact of Psilocybin-Induced Subjective Experiences on Prolonged Grief Disorder

Overview

This study will investigate whether a single dose of psilocybin, combined with psychological support, can help individuals experiencing Prolonged Grief Disorder (PGD) process their loss and begin to heal. Through this research, investigators will explore both personal experiences and brain activity to assess psilocybin’s potential to promote emotional integration, cognitive flexibility, and lasting relief from persistent grief.

Abstract

Prolonged Grief Disorder (PGD) is a debilitating condition marked by persistent yearning, identity disruption, and difficulty integrating the loss of a loved one. Affecting approximately 10% of bereaved individuals, PGD remains challenging to treat, with current interventions demonstrating limited efficacy. Recent evidence suggests that psilocybin, a serotonin 2A receptor agonist, may promote therapeutic emotional breakthroughs, increase cognitive flexibility, and enhance neuroplasticity. This open-label feasibility study examines the impact of a single 25 mg dose of psilocybin on PGD symptoms, subjective experience, and neural activity in young and emerging adults with PGD.

The study employs a mixed-methods design integrating standardized clinical assessments, micro-phenomenological interviews (MPIs), and functional magnetic resonance imaging (fMRI). Primary outcomes include changes in PGD symptom severity, openness to experience, and psychological flexibility. Secondary outcomes assess the predictive role of subjective experiences—particularly mystical-type experiences—on clinical improvement, and neural changes in the default mode network (DMN), anterior cingulate cortex (ACC), and amygdala.

Thirty participants will be enrolled, with a target of at least 20 completing all phases, including baseline and follow-up assessments at 1, 3, and 6 months. The study will analyze changes using linear mixed-effects models and thematic analysis of MPI transcripts. Neuroimaging data will be analyzed using both seed-based and task-based approaches to evaluate connectivity and activation changes.

Broader Impact

This study is among the first to investigate psilocybin’s therapeutic potential for PGD and the associated psychological and neural mechanisms. By integrating first-person accounts with neurobiological data, it aims to provide a comprehensive understanding of how psilocybin facilitates shifts in perception and emotional processing. Findings will inform the development of scalable, evidence-based interventions for grief and contribute to the broader field of psychedelic-assisted psychotherapy.