Stratification and Treatment in Early Psychosis Study - PROMOTE

The purpose of this trial is: * To investigate whether cannabidiol (CBD), compared to placebo, can reduce the severity of attenuated psychotic symptoms in individuals at clinical high risk for psychosis. * To confirm the safety of CBD in individuals at clinical high risk for psychosis. The trial is a randomised, double-blind, placebo-controlled, multi-centre, international clinical trial. Individuals meeting clinical high risk for psychosis criteria will be recruited for the trial intervention component of the trial. Participants are randomised to treatment with oral CBD 300mg (oral solution 100 mg/mL) twice daily, or a matching placebo, for 104 weeks. By using a battery of clinical outcome assessments, the trial will be able to assess several biomarkers to predict clinical outcomes and response to treatment with CBD. Participants will be invited to provide blood samples, stool samples, cerebrospinal fluid samples (if aged 18 years or over) and complete neuroimaging assessments. Individuals who are not found to have mental illness as defined by DSM-5 criteria will be recruited to a healthy control group, to validate the biomarker component of the trial. Additionally, a control group of healthy volunteers will be recruited who will not take the trial intervention to aid calibration between datasets from sites acquiring MRI data and to inform and validate any possible multivariate signature associated with the CHR-P state, course or outcome by understanding how these measures are different in controls. Healthy controls will also be used for secondary case-control comparisons. Healthy controls will undergo clinical and biomarker assessments only.

CHR-P patients: Inclusion Criteria 1. 12 to 35 years of age inclusive, willing and able to provide written informed consent/assent. 2. Meet criteria for either the Attenuated Psychotic Symptoms (APS) or Brief Limited Intermittent Psychotic Symptoms (BLIPS) subgroups of the CHR-P state, defined using the CAARMS (PSYSCAN version), which also integrates the SIPS criteria. Inter-rater reliability will be ensured throughout via an ongoing training programme for the researchers at each site. 3. The participant is currently not participating and is not expecting to start participation during the current trial in another intervention trial (e.g. medication, medical device, psychological intervention). 4. Participants of childbearing potential\* must be willing to ensure that they use highly effective contraception during the trial as per the requirements in the protocol\*\* 5. For participants who take part in the optional MRI scans: they must be eligible for MRI scanning as per local requirements, for example concerning implants or braces. 6. For participants who take part in optional CSF collection: they must be aged 18 years or over, have excluded intracranial hypertension through MRI, be within the reference ranges in coagulation tests, have a BMI ≤32kg/m2, and have no medical or surgical conditions in which a lumbar puncture is contraindicated. The age range for eligibility has been applied as this corresponds to the usual age range for a clinical high-risk state; individual cases outside of this age range may have a different aetiology and/or prognosis which could impact on the trial outcomes. 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. There is no special requirement for male participants to use highly effective contraception as there are no known safety concerns in males, such as sperm toxicity, as per the investigator's brochure. This trial will also not be collecting male participant partner pregnancy data. \*A person is considered of childbearing potential, i.e. fertile, following menarche and until becoming postmenopausal 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 trial and for 3 months after any trial drug administration, unless surgically sterile or postmenopausal (no menses for 12 months without an alternative medical cause). 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\