Substantial Treatment-Seeking Interest, Narrow Eligibility: Diagnostic Heterogeneity and External Validity in the PRIDE Psilocybin Trial—Relevance to Precision Psychiatry

Public and patient interest in psychedelic-assisted psychotherapy is increasing, but people seeking access to psychedelic trials may be more clinically heterogeneous than the populations these trials can enrol. We conducted a cross-sectional descriptive analysis of previously unreported aggregate telephone-screening data from the coordinating site of PRIDE, an ongoing Italian multicentre phase II randomized trial comparing psilocybin with personalized neuromodulation for treatment-resistant depression (TRD). Among 67 candidates screened between November 2025 and June 2026, 54 were excluded (80.6%), eight were enrolled and treated (11.9%), and five were preliminarily eligible (7.5%). The leading reason for exclusion was absence of protocol-defined TRD or another psychiatric diagnosis (27/54, 50.0%), followed by age outside the protocol range (18.5%), current suicidal or self-harm ideation (13.0%), and substance use disorder or dependence (9.3%). The diagnostic diversity of excluded candidates highlights the gap between a narrowly defined trial population and heterogeneous treatment-seeking individuals. These screening data do not address treatment response or individualized treatment selection, but they help contextualize recruitment yield and the external validity of psychedelic trials. Trial registration: Clinical Trials Information System, EU CT No. 2024-519844-34-03.