The purpose of this trial is:
* To investigate whether the response to clozapine treatment can be enhanced by adding cannabidiol (CBD), compared to placebo, in treatment resistant psychosis patients.
* To confirm the safety of CBD in people with psychosis.
The trial is a randomised, double-blind, placebo-controlled, multi-centre, international, clinical trial. Individuals with a diagnosis of treatment resistant psychosis in their illness who have had a suboptimal or no response to clozapine treatment will be recruited. These patients are randomised to treatment with oral CBD 500mg twice daily, or a matching placebo for 12 weeks, in addition to clozapine, which is standard care treatment for this population. By using a battery of clinical outcome assessments, the trial will assess several optional biomarkers 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 additional blood samples, stool samples, and complete neuroimaging assessments.
Who can participate
Age range
16 Years – 50 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. 16 to 50 years of age (inclusive) who are willing and able to provide written informed consent/assent (country specific requirements apply).
. The patient has been treated with clozapine for at least 8 weeks with a clozapine plasma concentration of at least 0.35 mg/L at screening. If a patient has a lower plasma concentration at screening, the patient can enter the trial at a later date once their plasma concentration is above the threshold\*.
. Within 10 years of first antipsychotic treatment prescribed for psychosis.
. The patient meets DSM-5 criteria for schizophrenia, schizoaffective disorder or schizophreniform disorder, as confirmed through the SCID-5-RV. The patient does not meet modified Andreasen et al (2005) criteria for symptomatic remission cross-sectionally (time requirement does not apply), i.e., a severity rating score of no more than mild (score of \</=3) on 8 specified Positive and Negative Syndrome Scale (PANSS) positive and negative symptom items: P1 - Delusions, P2 - Conceptual Disorganization, P3 - Hallucinatory Behaviour, N1 - Blunted Affect, N4 - Passive/Apathetic Social Withdrawal, N6 - Lack of Spontaneity and Flow of Conversation, G5 - Mannerisms and Posturing, G9 - Unusual Thought Content.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Change in Positive and Negative Syndrome Scale (PANSS) total score
. Patients of child-bearing potential\*\* must be willing to ensure that they use highly effective contraception during the trial and as per the requirements in the protocol\*\*\*.
. In the Investigator's opinion, is able and willing to comply with all trial requirements.
. Willing to allow their General Practitioner and/or consultant, if required by local guidelines/regulations, to be notified of participation in the trial.
. For patients 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.
Exclusion criteria
. Current treatment with sodium valproate, valproate semisodium, or clobazam. In cases of current use of these medicines, participation is only permitted if they can and will be discontinued or switched to a suitable alternative medication prior to randomisation.
. Hypersensitivity to the active substance, sesame oil, sesame seed or any of the excipients of the trial intervention.
. Known hepatic insufficiency and/or transaminase elevations levels exceeding the upper limit of normal 2 times or more and bilirubin greater than 1.5 times the upper limit of normal.
. Previous neurosurgery or neurological disorder, including epilepsy, which may affect the trial procedures\*.
. IQ \<70 as measured by a validated IQ test e.g. Wechsler Abbreviated Scale of Intelligence (WASI), Wechsler Adult Intelligence Scale (WAIS), and Wechsler Intelligence Scale for Children (WISC), as approved for local languages and appropriate for the participant's age.
. Pregnancy or breastfeeding.
. The patient has a current diagnosis of 'Substance or medication induced psychotic disorder' or 'Psychotic disorder due to another medical condition' as determined through the SCID-5-RV.
. Current active suicidal ideation within the last 2 weeks, defined as 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\*\*