Stratification and Treatment in Early Psychosis Study - PROMOTE

Exclusion Criteria

• •1. Previous neurosurgery or neurological disorder, including epilepsy, which may affect the trial procedures;\*
• •2. Pregnancy or breastfeeding;
• •3. The participant is unable to fully comprehend the purpose of the trial or make a rational decision whether or not to participate;
• •4. IQ\<70 as measured by a validated IQ test e.g. WASI, WAIS, WISC, as approved for local languages and appropriate for the participant's age;
• •5. Meeting DSM-5 criteria for substance use disorder, with the exception of nicotine use disorder (mild, moderate, and severe allowed). Mild cannabis use disorder is allowed (i.e. can meet up to but no more than 3 criteria on the SCID-5-RV) as long as the subject has not consumed cannabis on average more than three times a week in the past 30 days. Mild alcohol use disorder is also allowed;
• •6. Antipsychotic exposure: any antipsychotic medication in the two weeks before screening at doses adequate for treating FEP (≥ minimum effective dose); or antipsychotic medication for longer than a cumulative total of 30 days in the 3 months before screening at doses adequate for treating FEP (≥ minimum effective dose);\*\*
• •7. Any past episode of frank psychosis (excluding BLIPS);
• •8. Hypersensitivity to the active substance, sesame oil, sesame seed, or any of the excipients listed in section 3.3 of the IB;
• •9. Current treatment with valproate (including valproic acid, sodium valproate, valproate semisodium);
• •10. Current treatment with clobazam;
• •11. Known hepatic insufficiency and/or transaminase levels exceeding the upper limit 2 times or more and bilirubin greater than 1.5 times the upper limit of normal;
• •12. Active suicidal ideation within the past 2 weeks (a score of 1 or higher on CDSS question 8, followed by an assessment by the treating clinician who determines it is not safe for the patient to participate in the trial) or presence of risk (e.g. violence) \*\*\*;
• •13. The participant has participated in another research study in which the participant received an experimental or investigational drug or intervention within 3 months before Visit 0;
• •14. The participant refuses or cannot do any mandatory safety checks during the trial, specifically, refusal of: pregnancy test (those of childbearing potential only); safety blood tests; reporting of adverse events; or assessment of suicidality;
• •15. Those of childbearing potential not willing to use a highly effective form of contraception during participation in the trial. There is inadequate information on the effects of cannabidiol on the foetus. Participants of childbearing potential should use a highly effective method of contraception for the duration of the main trial and for 3 months after any administration of trial intervention;
• •16. Traumatic brain injury that is rated as 7 or above on the Traumatic Brain Injury screening instrument.
• •* Minor neurological disorders such as migraine, other minor headache disorders, sleep disorders or nerve palsies that are unlikely to affect trial or biomarker outcomes can be permitted.
• •* If at screening, a potential participant is prescribed an antipsychotic at a dose ≥ minimum effective dose for treating FEP, they may be re-screened for trial participation at a later date if the dose is subsequently reduced below threshold for at least 2 weeks. Any decision to do so will be the responsibility of the treating clinician and must ensure that it is both safe and ethical to do so. Specialist advice will be made available and be provided by clinicians experienced in managing CHR-P at University of Oxford and King's College London.
• •* The decision to include the patient is at the clinician's discretion. In case of a score of 1 or higher in CDSS question 8, the clinician can conclude that it is safe for the patient to participate after the patient is evaluated, in which case this exclusion criterion does not apply and the patient can participate. Either way, the treating clinician needs to record his/her evaluation of suicidal risk in the source documentation or medical file, including his/her considerations, and notify the site PI of the decision.
• •Healthy controls:
• •1. Lifetime history of a DSM Axis-I psychiatric disorder as determined by the SCID-5-RV;
• •2. Lifetime history of meeting CHR-P state criteria;
• •3. First-degree relative with a lifetime history of affective or non-affective psychosis (defined by treatment or diagnosis);
• •4. Previous intake of antipsychotic medication at any dosage;
• •5. Current intake of psychoactive medication;
• •6. Previous neurosurgery or neurological disorder, including epilepsy, which may affect the trial procedures;
• •7. Pregnant or breastfeeding;
• •8. Participant is unable to fully comprehend the purpose of the trial or make a rational decision whether or not to participate;
• •9. IQ\<70 as measured by a validated IQ test e.g. WASI, WAIS, WISC, as approved for local languages and appropriate for the participant's age;
• •10. Any contraindications for MRI;
• •11. Refusing to have their blood drawn and/or their MRI performed.