Psychotic disorders like schizophrenia affect millions of people worldwide with life debilitating symptoms including hallucinations, delusions and confusion. There is a growing body of research to support the use of cannabidiol (CBD) to help reduce the symptoms of psychosis. Traditional anti-psychotic medications work by targeting the dopamine system whereas CBD works by modulating the endocannabinoid system giving an alternative treatment pathways for patients who have not found existing anti-psychotics effective at managing their symptoms.

The STEP programme, which will be conducted at sites in the UK and internationally, will investigate the effects of CBD in combination with prescribed anti-psychotics for different psychosis patient sub-groups and discover whether CBD could be used as anti-psychotic medication. STEP consists of three separate phase III, placebo controlled, double-blind, randomised trials; titled STEP-ENHANCE, STEP-PROMOTE and STEP-ASSIST. 

These trials will all investigate participants with early psychosis but have different specific study criteria. STEP-ENHANCE includes patients who have just had their first episode of psychosis, STEP-ASSIST includes patients who are experiencing treatment resistant psychosis, and STEP-PROMOTE includes patients who are at clinical high risk of developing psychosis.

The aims of all three trials are to:

1. Test whether CBD can enhance the response to anti-psychotic treatment and improve daily function and quality of life.
2. Understand how CBD works using information from blood tests and magnetic resonance imaging (MRI) brain scans.
3. Predict longer-term outcomes using information from questionnaires, blood tests and MRI brain scans where available.

The STEP programme will begin with some initial baseline questions and screening with a participant's healthcare provider and the trial team. If successful, they will be recruited into the appropriate trial.

The trials in the programme will test whether CBD is able to improve symptoms by comparing two groups of participants. These groups will be "randomised" by a computer, and neither the participant nor study staff will know which group a participant is in until the end of the trial. One group of participants will be given CBD and the other group will be given a placebo. Both groups will also remain on their standard treatment as prescribed by their doctors. The placebo looks, smells and tastes identical to CBD but does not contain any medicine.

Participants will take doses twice a day over the study period. They will also be asked to attend trial visits at their local hospital over this period (the number of which varies according to the particular trial), where trial staff will take blood samples for safety and substance monitoring purposes (and urine samples if necessary), conduct physical examinations, and ask questions about participants' symptoms, medications, and experiences.

Optionally, participants may also elect to take part in two MRI brain scan sessions to help understand how CBD is working in the brain, provide additional blood samples for other measurement purposes, and provide a stool sample to see whether there are interactions between microorganisms in your gut and CBD, and further assess your body's response to the treatment. All of these elements will take place over the span of the trial visit period.

The remainder of the trial consists of a period of post treatment safety monitoring after the end of the trial, and optionally a long-term follow up at twelve weeks (STEP-ASSIST), one year (STEP-ENHANCE), or two years (STEP-PROMOTE) depending on which study they are signed up for.

Participants will be reimbursed for travel expenses, time and inconvenience, which will be arranged by their local trial team. 

Stratification and Treatment in Early Psychosis: AugmENtation witH cAnnabidiol iN first episode psyChosis: a doublE blind randomised controlled trial.

The STEP-ENHANCE trial will involve 250 participants from the UK and around the world who have just had their first episode of psychosis and who are still experiencing some symptoms despite being prescribed anti-psychotic medication by their doctor. Participants will take doses of CBD or the placebo over a period of six weeks, with six trial visits with staff at their local hospital and a subsequent monitoring period of three months with an optional one year long-term follow-up.

STEP-ENHANCE will recruit in countries: Austria, Germany, Greece, Israel, Italy, The Netherlands, Spain and the UK.

To find out more about the trial and to see if you are eligible to take part in the trial, please see the participant information sheet.

Stratification and Treatment in Early Psychosis: ImPRoving OutcoMes in individuals at clinical high risk fOr Psychosis using cannabidiol: a double-blind, randomised conTrollEd trial

The STEP-PROMOTE trial will involve 376 participants from the UK and around the world who are at clinical high risk of developing psychosis. Participants will take doses of CBD or the placebo over a period of 104 weeks, with 11 trial visits with staff at their local hospital and a subsequent monitoring period.

STEP-PROMOTE will recruit in countries: Austria, Canada, Finland, Germany, Greece, Italy, The Netherlands, Spain, Switzerland and the UK.

To find out more about the trial and to see if you are eligible to take part in the trial, please see the participant information sheet.

Stratification and Treatment in Early Psychosis: Cannabidiol augmentation of clozapine in treatment resistant psychosis: a double-blind randomised controlled trial

The STEP-ASSIST trial will involve participants who are still experiencing symptoms of psychosis after taking clozapine. Participants will take doses of CBD or the placebo over a period of twelve weeks, with seven trial visits with staff at their local hospital and a subsequent monitoring period.  

STEP-ASSIST will recruit in countries: Canada, Germany, Greece, Israel, Italy, Spain, Switzerland, The Netherlands, and the UK.

To find out more about the trial and to see if you are eligible to take part in the trial, please see the participant information sheet.

Wellcome Trust.

GW Pharmaceuticals, part of Jazz Pharmaceuticals (support in kind)

Eleven clinical trials that will shape medicine in 2025, Nature Medicine, 12 Dec 2024

Oxford study to trial cannabis-based medicine as treatment for psychosis, The Guardian, 16 Feb 2023

CBD treatment for psychosis to be tested in major international study, Sky News, 16 Feb 2023