Stratification and Treatment in Early Psychosis Study - ENHANCE

The purpose of this study is: * To investigate whether the response to antipsychotic treatment can be enhanced by adding cannabidiol (CBD) to the existing treatment, compared to placebo, in participants with a first episode of psychosis, who have had a suboptimal or no response to their first antipsychotic treatment. * To confirm the safety of CBD in people with psychosis. The study is a randomized, double-blind, placebo-controlled, multi-centre, clinical trial. Individuals with a diagnosis of first-episode psychosis, who have had a suboptimal or no response to their first antipsychotic treatment will be recruited. These participants are randomised to treatment with CBD oral solution 500mg twice daily, or a matching placebo for 6 weeks, as an adjunct to their existing antipsychotic treatment. By using a battery of clinical outcome assessments, the trial will also assess several biomarkers to determine if they can be used to predict clinical outcomes and response to treatment with CBD. Biomarkers are being assessed as an exploratory outcome measure. Participants will be invited to provide blood and stool samples, and may be asked to complete neuroimaging assessments at certain eligible sites.

NCT Number	NCT06778564
Lead Sponsor	University of Oxford Collaborators: Wellcome Trust, Cambridge Cognition Ltd, Cambridgeshire and Peterborough NHS Foundation Trust, Oxford Health NHS Foundation Trust, West London NHS Trust, Charite University, Berlin, Germany, University of Cologne, Ludwig-Maximilians - University of Munich, The Sheba Fund for Health Services and Research, Shalvata Mental Health Center, Geha Mental Health Center, Amsterdam University Medical Center, Hospital General Universitario Gregorio Marañon, National and Kapodistrian University of Athens, Medical University of Vienna, Hospitales Universitarios Virgen del Rocío, University of Campania Luigi Vanvitelli, Psychiatric University Hospital, Zurich
Conditions	Psychosis, First Episode Psychosis, Psychotic Disorders, Psychotic Episode
Enrollment	250 participants
Start Date	2026-02
Primary Completion	2028-02 (estimated)
Study Completion	2029-02 (estimated)
Updated on ClinicalTrials.gov	2025-12-12