INTERVENTIONALNOT YET RECRUITINGNCT07434973

ImPRoving OutcoMes in Individuals at Clinical High Risk fOr Psychosis Using Cannabidiol: a Double-blind, Randomised conTrollEd Trial

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.

Locally preserved from ClinicalTrials.govOpen ClinicalTrials.govlast source update 2026-02-27

What this record can show

Protocol only - no registry results posted

This locally preserved record separates the registered protocol from source-reported registry results. Neither is a treatment recommendation.

Registry facts

Study at a glance

Phase: PHASE3
Enrollment: 586 (ESTIMATED)
Start date: 2026-05-01
Sponsor: University of Oxford
Design: RANDOMIZED · PARALLEL · TREATMENT
Locations: 19
Results record: Not present in registry snapshot

Linked local records

Related local records

Local links use governed condition terms or exact source-reported intervention names. They are navigation candidates, not efficacy claims.

Conditions

No published condition report matched.

Cannabinoids and active compounds

cannabidiol

Medicines

No exact medicine-name link was found.

Interventions

What was registered

DRUG

Cannabidiol (CBD)

CBD 100 mg/mL Oral Solution

DRUG

Placebo

Placebo for Cannabidiol oral solution 100mg/mL oral solution

Eligibility

Population and criteria

Sex: ALL
Minimum age: 12 Years
Maximum age: 35 Years
Healthy volunteers: Accepted

secondary measures

Change in attenuated psychotic symptoms (Comprehensive Assessment of At-Risk Mental States, CAARMS total score)

Time frame: Baseline to Week 4

Change from baseline to Week 4 in CAARMS (Comprehensive Assessment of At-Risk Mental States) total score

Change in attenuated psychotic symptom subscale scores (Comprehensive Assessment of At-Risk Mental States, CAARMS P1-P4)

Time frame: Baseline to Week 4

Change from baseline to Week 4 in Comprehensive Assessment of At-Risk Mental States (CAARMS) P1-P4 subscale scores.

Change in distress associated with attenuated psychotic symptoms

Time frame: Baseline to Week 4

Change from in Comprehensive Assessment of At-Risk Mental States (CAARMS) distress scores.

Change in anxiety symptoms (Hamilton Anxiety Rating Scale, HAM-A)

Time frame: Baseline to Week 4

Change from baseline to Week 4 in Hamilton Anxiety Rating Scale (HAM-A) total score.

Change in anxiety symptoms (Overall Anxiety Severity and Impairment Scale, OASIS)

Time frame: Baseline to Week 4

Change from baseline to Week 4 in Overall Anxiety Severity and Impairment Scale (OASIS) score

Remission from Clinical High-Risk for Psychosis (CHR-P) state

Time frame: Baseline to Week 4

Proportion of participants meeting Comprehensive Assessment of At-Risk Mental States (CAARMS) remission criteria at Week 4.

Change in quality of life (EQ-5D-3L index score)

Time frame: Baseline to Week 4

Change from baseline to Week 4 in EQ-5D-3L index score.

Change in quality of life (WHOQOL-BREF total score)

Time frame: Baseline to Week 4

Change from baseline to Week 4 in WHOQOL-BREF total score.

All-cause treatment discontinuation

Time frame: Baseline to Week 4

Proportion of participants who discontinue study treatment for any reason by Week 4.

Incidence of adverse events

Time frame: Baseline to Week 4

Number of participants with one or more adverse events by Week 4.

Severity of adverse events (Glasgow Antipsychotic Side-effect Scale, GASS total score)

Time frame: Baseline to Week 4

Change from baseline to Week 4 in Glasgow Antipsychotic Side-effect Scale (GASS) total score.

Change in clinician-rated global severity (Clinical Global Impressions (CGI) scale- - Severity, CGI-S)

Time frame: Baseline to Week 4

Change from baseline to Week 4 in Clinical Global Impressions scale- - Severity (CGI-S) score.

Change in clinician-rated global severity (Clinical Global Impressions (CGI) scale- - Improvement, CGI-I)

Time frame: Baseline to Week 4

Change from baseline to Week 4 in Clinical Global Impressions scale- - Improvement (CGI-I) score.

Change in patient-rated global severity (Patient Global Imression of Improvement, PGI-I)

Time frame: Baseline to Week 4

Change from baseline to Week 4 in Patient Global Imression of Improvement (PGI-I) score.

Change in patient-rated global severity (Patient Global Impression of Severity, PGI-S)

Time frame: Baseline to Week 4

Change from baseline to Week 4 in Patient Global Imression of Severity (PGI-S) score.

Change in attenuated psychotic symptoms (Comprehensive Assessment of At-Risk Mental States, CAARMS total score)

Time frame: Baseline to Week 104

Change in attenuated psychotic symptom subscale scores (Comprehensive Assessment of At-Risk Mental States, CAARMS P1-P4)

Time frame: Baseline to Week 104

Change in anxiety symptoms (Hamilton Anxiety Rating Scale , HAM-A)

Time frame: Baseline to Week 104

Change in anxiety symptoms (Overall Anxiety Severity and Impairment Scale, OASIS)

Time frame: Baseline to Week 104

Change in global functioning (Social and Occupational Functioning Assessment Scal, SOFAS)

Time frame: Baseline to Week 104

Change in cognitive functioning (PsyCog battery composite score)

Time frame: Baseline to Week 104

Transition to psychosis

Time frame: Baseline to Week 104

Proportion of participants meeting Comprehensive Assessment of At-Risk Mental States (CAARMS) criteria for transition to psychosis. Biomarker data (neuroimaging, peripheral blood, microbiome, metabolomics, proteomics, CSF and environmental measures) will be used in exploratory modelling analyses to develop prognostic and predictive algorithms for transition to psychosis and treatment response.

Remission from Clinical High-Risk for Psychosis (CHR-P) state

Time frame: Baseline to Week 104

Change in quality of life (EQ-5D-3L)

Time frame: Baseline to Week 104

Change in quality of life (WHOQOL-BREF)

Time frame: Baseline to Week 104

All-cause treatment discontinuation

Time frame: Baseline to Week 104

Incidence of adverse events

Time frame: Baseline to Week 104

Severity of adverse events (Glasgow Antipsychotic Side-effect Scale, GASS)

Time frame: Baseline to Week 104

Change in clinician-rated global impression (CGI)

Time frame: Baseline to Week 104

Change in patient-rated global impression (PGI)

Time frame: Baseline to Week 104

Diagnosis of mental disorders

Time frame: Baseline, Week 104, and 4 years post-baseline

Proportion of participants diagnosed with a mental disorder based on clinical record review. Biomarker data (neuroimaging, peripheral blood, microbiome, metabolomics, proteomics, CSF and environmental measures) will be used in exploratory modelling analyses to develop prognostic and predictive algorithms for transition to psychosis and treatment response.

Prescription of psychotropic medication

Time frame: Baseline, Week 104, and 4 years post-baseline

Proportion of participants prescribed psychotropic medication. Biomarker data (neuroimaging, peripheral blood, microbiome, metabolomics, proteomics, CSF and environmental measures) will be used in exploratory modelling analyses to develop prognostic and predictive algorithms for transition to psychosis and treatment response.

Psychiatric hospital or emergency department admission

Time frame: Baseline, Week 104, and 4 years post-baseline

Proportion of participants admitted to psychiatric hospital or emergency services. Biomarker data (neuroimaging, peripheral blood, microbiome, metabolomics, proteomics, CSF and environmental measures) will be used in exploratory modelling analyses to develop prognostic and predictive algorithms for transition to psychosis and treatment response.

Number of healthcare appointments

Time frame: Baseline to 4 years post-baseline

Total number of healthcare appointments recorded. Biomarker data (neuroimaging, peripheral blood, microbiome, metabolomics, proteomics, CSF and environmental measures) will be used in exploratory modelling analyses to develop prognostic and predictive algorithms for transition to psychosis and treatment response.

Mortality (including suicide)

Time frame: Baseline to 4 years post-baseline

All-cause mortality, including suicide. Biomarker data (neuroimaging, peripheral blood, microbiome, metabolomics, proteomics, CSF and environmental measures) will be used in exploratory modelling analyses to develop prognostic and predictive algorithms for transition to psychosis and treatment response.

Change in environmental risk score (Psychosis Polyrisk Score, PPS)

Time frame: Baseline to Week 104

Change in psychopathology (Semi-structured Interview for Bipolar At Risk States, SIBARS score)

Time frame: Baseline to Week 104

Change in psychopathology (Young Mania Rating Scale, YMRS score)

Time frame: Baseline to Week 104

Change in borderline personality features (McLean Screening Instrument for borderline personality disorder, MSI-BPD score)

Time frame: Baseline to Week 104

Change in daily functioning (Functional Remission of General Schizophrenia, FROGS score)

Time frame: Baseline to Week 104

Change in physical activity (Simple Physical Activity Questionnaire, SIMPAQ score)

Time frame: Baseline to Week 104

Change in resilience (Resilience Scale for Adults, RSA score)

Time frame: Baseline to Week 104

Change in substance use (Alcohol, Smoking and Substance Involvement Screening Tool, ASSIST score)

Time frame: Baseline to Week 104

Protocol only - no registry results posted

Study at a glance

Related local records

Conditions

Cannabinoids and active compounds

Medicines

What was registered

Cannabidiol (CBD)

Placebo

Population and criteria

Eligibility criteria

Inclusion criteria

Exclusion criteria

Inclusion criteria

Exclusion criteria

primary measures

ChaChange from baseline in attenuated positive psychotic symptoms (CAARMS P1-P4 positive symptom subscale score)

secondary measures

Change in attenuated psychotic symptoms (Comprehensive Assessment of At-Risk Mental States, CAARMS total score)

Change in attenuated psychotic symptom subscale scores (Comprehensive Assessment of At-Risk Mental States, CAARMS P1-P4)

Change in distress associated with attenuated psychotic symptoms

Change in anxiety symptoms (Hamilton Anxiety Rating Scale, HAM-A)

Change in anxiety symptoms (Overall Anxiety Severity and Impairment Scale, OASIS)

Remission from Clinical High-Risk for Psychosis (CHR-P) state

Change in quality of life (EQ-5D-3L index score)

Change in quality of life (WHOQOL-BREF total score)

All-cause treatment discontinuation

Incidence of adverse events

Severity of adverse events (Glasgow Antipsychotic Side-effect Scale, GASS total score)

Change in clinician-rated global severity (Clinical Global Impressions (CGI) scale- - Severity, CGI-S)

Change in clinician-rated global severity (Clinical Global Impressions (CGI) scale- - Improvement, CGI-I)

Change in patient-rated global severity (Patient Global Imression of Improvement, PGI-I)

Change in patient-rated global severity (Patient Global Impression of Severity, PGI-S)

Change in attenuated psychotic symptoms (Comprehensive Assessment of At-Risk Mental States, CAARMS total score)

Change in attenuated psychotic symptom subscale scores (Comprehensive Assessment of At-Risk Mental States, CAARMS P1-P4)

Change in anxiety symptoms (Hamilton Anxiety Rating Scale , HAM-A)

Change in anxiety symptoms (Overall Anxiety Severity and Impairment Scale, OASIS)

Change in global functioning (Social and Occupational Functioning Assessment Scal, SOFAS)

Change in cognitive functioning (PsyCog battery composite score)

Transition to psychosis

Remission from Clinical High-Risk for Psychosis (CHR-P) state

Change in quality of life (EQ-5D-3L)

Change in quality of life (WHOQOL-BREF)

All-cause treatment discontinuation

Incidence of adverse events

Severity of adverse events (Glasgow Antipsychotic Side-effect Scale, GASS)

Change in clinician-rated global impression (CGI)

Change in patient-rated global impression (PGI)

Diagnosis of mental disorders

Prescription of psychotropic medication

Psychiatric hospital or emergency department admission

Number of healthcare appointments

Mortality (including suicide)

Change in environmental risk score (Psychosis Polyrisk Score, PPS)

Change in psychopathology (Semi-structured Interview for Bipolar At Risk States, SIBARS score)

Change in psychopathology (Young Mania Rating Scale, YMRS score)

Change in borderline personality features (McLean Screening Instrument for borderline personality disorder, MSI-BPD score)

Change in daily functioning (Functional Remission of General Schizophrenia, FROGS score)

Change in physical activity (Simple Physical Activity Questionnaire, SIMPAQ score)

Change in resilience (Resilience Scale for Adults, RSA score)

Change in substance use (Alcohol, Smoking and Substance Involvement Screening Tool, ASSIST score)

Locally readable linked articles