Stratification and Treatment in Early Psychosis Study - ENHANCE

Inclusion Criteria

• •1. The participant is 16 to 40 years of age, willing and able to provide written informed consent/assent.
• •2. The participant is currently being treated with an antipsychotic for at least 3 weeks but no longer than 16 weeks.
• •3. The participant should be receiving at least the minimum dose of this antipsychotic for FEP according to modified Maudsley guidelines, as listed in Appendix B. The clinician should judge the participant to be a non-responder to this treatment and that increasing the dose further is unacceptable to the clinician and/or participant.
• •4. The compliance score associated with this antipsychotic medication is 4 or more on the Clinician Rating Scale (CRS).
• •5. The participant meets DSM-5 criteria for schizophrenia, schizoaffective disorder or schizophreniform disorder, as confirmed through the SCID-5-RV.
• •6. The participant does not meet modified Andreasen criteria for symptomatic remission (time requirement does not apply).
• •7. Participants of childbearing potential (\*) must be willing to ensure that they use highly effective contraception during the trial and as per the requirements in the protocol\*\*.
• •8. In the Investigator's opinion, is able and willing to comply with all trial requirements.
• •9. Willing to allow their General Practitioner and/or consultant, if required by local guidelines/regulations, to be notified of participation in the trial.
• •10. For participants who take part in the optional MRI scans: they must be eligible for MRI scanning as per local requirements, for example concerning e.g. implants, braces etc.
• •There is inadequate information on the effects of cannabidiol on the foetus in humans. Participants of childbearing potential\* should use a highly effective method of contraception\*\* for the duration of the trial and for 3 months after the last time the trial intervention was used.
• •\*A person is considered of childbearing potential, i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
• •\*\* Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include: 1) combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral; intravaginal; transdermal); 2) progestogen-only hormonal contraception associated with inhibition of ovulation (oral; injectable; implantable); 3) intrauterine device (IUD); 4) intrauterine hormone-releasing system (IUS); 5) bilateral tubal occlusion; 6) vasectomised partner; 7) sexual abstinence (abstinence should only be used as a contraceptive method if it is in line with the participants' usual and preferred lifestyle).
• •Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not an acceptable method of contraception. The participant agrees to use an acceptable method of contraception\* for the duration of the study and for 3 months after any study drug administration, unless surgically sterile or postmenopausal (no menses for 12 months without an alternative medical cause).
• •The age range for eligibility has been applied as this corresponds to the usual age range for first episode psychosis; individual cases outside of this age range may have a different aetiology and/or prognosis which could impact on the study outcomes.