Substantial Treatment-Seeking Interest, Narrow Eligibility: Diagnostic Heterogeneity and External Validity in the PRIDE Psilocybin Trial—Relevance to Precision Psychiatry
Antonio Inserra, Luca Persico, Arianna Rosati, Mara Fabale, Clara Cavallotto, Giacomo D’andrea, Francesca Zoratto, Mauro Pettorruso, Luisa de Risio, Antonio Ventriglio, Antonello Bellomo, Giuseppe Nicolò, Giovanni Martinotti
Behavioral Sciences October 26, 2026 DOI: 10.3390/bs16111997 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Cross-sectional descriptive analysis Randomized Peer reviewed |
|---|---|
| Sample size | 67 |
| Population | People who contacted the coordinating site of an Italian multicentre phase II trial to be screened as candidates for psilocybin-assisted treatment of treatment-resistant depression |
| Topics | Psilocybin |
| Key findings | Of 67 screened candidates, 54 (80.6%) were excluded, eight (11.9%) were enrolled and treated, and five (7.5%) were preliminarily eligible. The leading exclusion reason was absence of protocol-defined treatment-resistant depression 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 authors contend these results illustrate a gap between narrowly defined trial populations and heterogeneous treatment-seeking individuals. |
Abstract
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.
Comparable studies
Other cross-sectional and survey studies on psilocybin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences Individuals who had consumed psilocybin mushrooms and experienced a psychologically... | 2016 | Cross-sectional survey | n = 1,993 |
| The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms Internet survey respondents reporting challenging experiences with psilocybin | 2016 | Questionnaire development and validation | |
| Psychedelics and Mental Health: A Population Study Adult population in the United States | 2013 | Cross-sectional survey | n = 130,152 |
| Cessation and reduction in alcohol consumption and misuse after psychedelic use Individuals with prior alcohol use disorder who reported cessation or reduction in... | 2019 | Cross-sectional survey | n = 343 |
| Patterns of simultaneous polysubstance use in drug using university students Drug-using university students | 2006 | Cross-sectional survey | n = 149 |