Ground-breaking nature of the project Many of the expected impacts from this proposal are innovative. It aims to demonstrate that biomarkers can be used to stratify patients in the early phase of psychosis according to clinical outcomes, and that this can improve clinical care by providing a basis for more personalised treatment. Moreover, these biomarkers include measures acquired by employing novel digital technologies in mobile devices, and the prediction of outcomes will be facilitated by new tools that generate personalised estimates of a given outcome. The project will also evaluate a new class of treatment for psychosis (Cannabidiol) and assess whether existing treatments are more effective when used in specific subgroups patients that have been identified through stratification. Finally, the project aims to create a global translational research platform for the evaluation of novel treatments. The long-term impact will include the following domains: - Conceptual shift in approach to assessment in psychosis - Clinical impact of stratification - New classes of treatment and therapeutic targets - Reorganisation of clinical services - Improved care for patients, carers and families - Translation of research - Collaboration with industry - Health economics benefits - Implementation of digital technology in the early phase of psychosis The STEP (Stratification & Treatment in Early Psychosis) programme leverages cutting edge multimodal neuroscientific methods across four studies and twenty research centres worldwide with the overarching aim of improving the care for young people experiencing emerging psychotic disorders: Aim 1. Stratification of patients in the early phase of psychosis 500 individuals at clinical risk for psychosis (CHR), 100 healthy controls and 500 individuals with a first episode of psychosis (FEP) will undergo a comprehensive baseline assessment with cutting edge biomarkers and clinical follow-up. Aim 2. Evaluation of novel treatments / treatment algorithms - Trial 1. 500 CHR individuals will receive treatment as usual with placebo or cannabidiol (600mg/day orally) in a 52-weeks double blind RCT. - Trial 2. 500 FEP individuals who have not responded to an initial course of antipsychotic will be givenopen-label, treatment with Amisulpride (200-800mg/day orally) and randomly allocated to adjunctive CBD (800mg/day; orally) or Placebo for 6 weeks. - Trial 3. 250 FEP individuals who are not in symptomatic remission at the end of the trial 2 (Treatment Resistant), will be invited in an open-label 12-weeks treatment with Clozapine (300-900mg/day orally), and random allocation to adjunctive treatment with CBD (1000mg) or Placebo. Aim 3. Development of clinical tools Development of a smartphone-based tool that can predict clinical outcomes in individuals with emerging psychosis. Aim 4. Construction of a global translational research network A global clinical research network that will serve as a platform for the evaluation of biomarkers, novel treatments, and the use of stratification to facilitate treatment evaluation.