Early PsychosisPhase 3NCT04411225

Effects of Cannabidiol (CBD) Versus Placebo as an Adjunct to Treatment in Early Psychosis

A Phase 3 study testing Cannabidiol oral solution in people with Early Psychosis, run by University of California, San Diego at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 16 to 30 years
Conditions the study is for: Early Psychosis
What is being tested?: Cannabidiol oral solution
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 120 participants
Where: 2 sitesUnited States
Study dates: 1 Jun 2022to Dec 2026
Phase: Phase 3
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 16 to 30 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

First episode psychosis (onset within the last 2 years) or attenuated psychosis syndrome (APS), stabilized with treatment for at least 8 weeks prior to initiating the trial consistent with the FDA-NIMH-MATRICS guidelines for clinical trial design for clinical enhancing drugs:
Clinically stable and in a nonacute phase of their illness for at least 2 months, First episode psychosis participants will have been maintained on current antipsychotic for at least 6 weeks, with no change in antipsychotic dose for the previous 4 weeks while APS participants will be on the same treatment regimen (psychosocial or pharmacologic) for 4 weeks,
Exhibit no more than moderate levels of positive symptoms (defined by ratings of ≤ 4) on PANSS items P1 (delusions), P2 (conceptual disorganization), P3 (hallucinatory behavior), P5 (grandiosity), P6 (suspiciousness), and G8 (unusual thought content),
No more than a minimal level of depressive symptoms as assessed by the Calgary Depression Scale for Schizophrenia (CDSS)
Acceptable diagnoses will include APS, Psychosis NOS, Schizophreniform, Schizophrenia, and Schizoaffective per the Structured Clinical Interview for DSM-V.

Who cannot join

Concomitant medical or neurological illness;
Significant head injury;
Impaired intellectual functioning IQ<80; however those with an IQ i the 75-79 range will be include if WRAT reading > 85 suggesting higher premorbid IQ.
High suicidal risk assessed by the The Columbia-Suicide Severity Rating Scale (C-SSRS)42
Pregnant women and those who do not agree to avoid becoming pregnant
Patients requiring treatment with Azelastine, Azelastine; Fluticasone, Dronabinol, Valproic Acid, or Divalproex Sodium

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Kristin Cadenhead contact

619-543-6445

KCADENHEAD@UCSD.EDU

United States2 sites, 2 recruiting

UC San Diego
La Jolla, California, 92093
Kristin Cadenhead, MD, 619-543-6445, kcadenhead@health.ucsd.edu
Heline Mirzakhanian, PhD, 619-543-7745, hmirzakhanian@health.ucsd.edu
Recruiting
University of California, San Diego
San Diego, California, 92093
Tracy Alderman, PhD, 619 543-7761, talderman@ucsd.edu
Kristin S Cadenhead, MD
Recruiting

Other trials in United States

About this study

Official title: Effects of Cannabidiol (CBD) Versus Placebo as an Adjunct to Treatment in Early Psychosis: Understanding the Mechanism and Mediators of Action

This is an outpatient, single center, between-group, double blind, placebo controlled design. Approximately 120 adolescents and adult patients will be randomized to either have their treatment augmented with Cannabidiol Oral Solution (CBD) or with a matching CBD placebo for 8 weeks. The study will examine CBD as an augmentation strategy in early psychosis. It is hypothesized that CBD will improve symptoms, neurocognition, markers of inflammation and eating behaviors. Importantly, moderators and mediators of the CBD effects will be explored.

Read the detailed description

Participants will be randomly assigned in a 1:1 ratio to receive CBD or matching Placebo as an add-on to antipsychotic medication in an 8 week double blind trial. In this study, Cannabidiol Oral Solution (CBD) product will be used. This product is manufactured and supplied by GW Pharmaceuticals. The formulation is a 100 mg/mL solution. The CBD compound will be dosed at 1000mg/day administered in two divided doses. The dose of CBD was selected based on previous controlled trials that demonstrate the efficacy of CBD in patients with schizophrenia.

The maximum duration of the study from screening to follow up of outcomes and adverse events will be approximately 8 weeks. Participants will receive either the CBD or placebo within this eight.weeks and will also complete pre-treatment, midpoint (week 4) and post-treatment testing (week 8).

Conditions: Early Psychosis
Being tested: Cannabidiol oral solution
Medical subject headings: Psychotic Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Cannabidiol oral solutionDrug
Also called Placebo
Both the active drug (cannabidiol) and placebo will be in oral solution.

Study groups in NCT04411225
Study group	Role	What they receive
Cannabidiol Augmentation	Experimental	The cannabidiol will be administered as an oral solution to be mixed in any fluid. The formulation is 100 mg/ml. It will be administered at 500 mg at bedtime X 1 week then 500 mg BID. Receives: Drug: Cannabidiol oral solution
Placebo Augmentation	Placebo comparator	Placebo will appear identical to the cannabidiol solution Receives: Drug: Cannabidiol oral solution

What is being measured

The primary outcome is the main question the study is designed to answer.

Positive and Negative Symptoms of Psychosis
Psychotic symptoms will be assessed with The Positive and negative psychotic syndrome scale (PANSS). This scale provides a summary score of all positive symptoms and all negative symptoms in participants who are already diagnosed with a psychotic disorder. The total score ranges from 30 to 210 with a higher score representing more symptoms.
Measured: Week 7
Neurocognition
A Global Cognition Score will be assessed with Measurement and Treatment Research in Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) in all subjects.The Global Cognitive Score is a composite of the Z scores across the different cognitive domains in the MCCB. The range of scores is -1 to +1. Positive scores represent better cognitive functioning.
Measured: week 7
Prodromal Symptoms
The Scale of Prodromal Symptoms (SOPS) is part of the Structured Interview for Prodromal Syndromes (SIPS) diagnostic interview. This scale will be used to assess subsyndromal psychotic symptoms in participants who are diagnosed as Clinical High Risk for Psychosis. Positive and Negative Symptoms will be assessed as summary scores of all positive or negative items The minimum score on the SOPS total is 0 and Maximum is 24. A higher score represents more symptoms.
Measured: Week 7
General Symptoms
The Brief Psychiatric Rating Scale (BPRS) will be used as an assessment of overall symptom ratings with a total score in all subjects. The minimum score is 24 and maximum is 168. A higher score represents more symptoms.
Measured: week 7
Clinical Global Impression Scale (CGI-S)
The CGI-S will provide a global psychopathology score for all subjects. The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. A "1" is considered normal while a "7" is extremely ill.
Measured: Week 7

Secondary outcomes (2)

Peripheral Biomarkers of Inflammation
Panel of chemokines and cytokines expressed as "Mean Concentration Value". The minimum and maximum value for each measure between 0 and 40,280. In general higher values represent greater immune activation.
Cytokines:
Interferon-gamma, Interleukin-1, Interleukin-6, Interleukin-10, Interleukin-12p70, Tumor Necrosis Factor- alpha,
Chemokines:
Eotaxin-1, Eotaxin-3, Fracktalkine, Interleukin-8, Interferon Gamma-Induced Protein-10, Monocyte Chemotactic Protein-1, Macrophage-Derived Chemokine, Macrophage Inflammatory Protein-1a, Macrophage Inflammatory Protein-1b, Thymus and Activation Regulated Chemokine,
Other:
Brain Derived Neurotropic Factor
Measured: week 7
Cortisol
AM Salivary Cortisol is normally in the range of 100-750 ng/dL. Higher levels are thought to represent a greater stress response.
Measured: 7 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jun 2022Dec 2026

First posted2 Jun 2020
Study start1 Jun 2022
Primary completionDec 2026 (estimated)
Study completionDec 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Early PsychosisStudies of the same condition, open and under way.
More trials run by University of California, San DiegoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: This is a between-group, double blind, placebo controlled design.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 120 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04411225
Sponsor's protocol ID: 649467 CMCR Grants Program
Other IDs: Cadenhead
Status last verified: Jan 2026
First submitted: 24 Apr 2020
Last updated: 8 Jan 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Dixon T, Cadenhead KS. Cannabidiol versus placebo as adjunctive treatment in early psychosis: study protocol for randomized controlled trial. Trials. 2023 Nov 30;24(1):775. doi: 10.1186/s13063-023-07789-w.
PubMed 38037108

Interested in taking part?

Kristin Cadenhead

619-543-6445

KCADENHEAD@UCSD.EDU

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

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All Early Psychosis trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of Cannabidiol (CBD) Versus Placebo as an Adjunct to Treatment in Early Psychosis: Understanding the Mechanism and Mediators of Action
ClinicalTrials.gov ID: NCT04411225
Acronym / sponsor ID: 649467 CMCR Grants Program
Conditions: Early Psychosis
Phase: Phase 3
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 120 participants (estimated)
Lead sponsor: University of California, San DiegoUniversity, hospital or other
Collaborators: Center for Medicinal Cannabis Research
Study start: 1 Jun 2022 (actual)
Primary completion: Dec 2026 (estimated)
Study completion: Dec 2026 (estimated)
First posted: 2 Jun 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2
Model description: This is a between-group, double blind, placebo controlled design.

Arm	Type	Receives
Cannabidiol Augmentation	Experimental	Drug: Cannabidiol oral solutionThe cannabidiol will be administered as an oral solution to be mixed in any fluid. The formulation is 100 mg/ml. It will be administered at 500 mg at bedtime X 1 week then 500 mg BID.
Placebo Augmentation	Placebo comparator	Drug: Cannabidiol oral solutionPlacebo will appear identical to the cannabidiol solution

Who may qualify

Ages: 16 to 30 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (5 listed)

First episode psychosis (onset within the last 2 years) or attenuated psychosis syndrome (APS), stabilized with treatment for at least 8 weeks prior to initiating the trial consistent with the FDA-NIMH-MATRICS guidelines for clinical trial design for clinical enhancing drugs:
Clinically stable and in a nonacute phase of their illness for at least 2 months, First episode psychosis participants will have been maintained on current antipsychotic for at least 6 weeks, with no change in antipsychotic dose for the previous 4 weeks while APS participants will be on the same treatment regimen (psychosocial or pharmacologic) for 4 weeks,
Exhibit no more than moderate levels of positive symptoms (defined by ratings of ≤ 4) on PANSS items P1 (delusions), P2 (conceptual disorganization), P3 (hallucinatory behavior), P5 (grandiosity), P6 (suspiciousness), and G8 (unusual thought content),
No more than a minimal level of depressive symptoms as assessed by the Calgary Depression Scale for Schizophrenia (CDSS)
Acceptable diagnoses will include APS, Psychosis NOS, Schizophreniform, Schizophrenia, and Schizoaffective per the Structured Clinical Interview for DSM-V.

Key exclusion criteria (6 listed)

Concomitant medical or neurological illness;
Significant head injury;
Impaired intellectual functioning IQ<80; however those with an IQ i the 75-79 range will be include if WRAT reading > 85 suggesting higher premorbid IQ.
High suicidal risk assessed by the The Columbia-Suicide Severity Rating Scale (C-SSRS)42
Pregnant women and those who do not agree to avoid becoming pregnant

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Cannabidiol oral solutionAlso: PlaceboBoth the active drug (cannabidiol) and placebo will be in oral solution.	Drug	Cannabidiol Augmentation, Placebo Augmentation

Primary outcome

Positive and Negative Symptoms of Psychosis
Time frame: Week 7
Psychotic symptoms will be assessed with The Positive and negative psychotic syndrome scale (PANSS). This scale provides a summary score of all positive symptoms and all negative symptoms in participants who are already diagnosed with a psychotic disorder. The total score ranges from 30 to 210 with a higher score representing more symptoms.
Neurocognition
Time frame: week 7
A Global Cognition Score will be assessed with Measurement and Treatment Research in Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) in all subjects.The Global Cognitive Score is a composite of the Z scores across the different cognitive domains in the MCCB. The range of scores is -1 to +1. Positive scores represent better cognitive functioning.
Prodromal Symptoms
Time frame: Week 7
The Scale of Prodromal Symptoms (SOPS) is part of the Structured Interview for Prodromal Syndromes (SIPS) diagnostic interview. This scale will be used to assess subsyndromal psychotic symptoms in participants who are diagnosed as Clinical High Risk for Psychosis. Positive and Negative Symptoms will be assessed as summary scores of all positive or negative items The minimum score on the SOPS total is 0 and Maximum is 24. A higher score represents more symptoms.
General Symptoms
Time frame: week 7
The Brief Psychiatric Rating Scale (BPRS) will be used as an assessment of overall symptom ratings with a total score in all subjects. The minimum score is 24 and maximum is 168. A higher score represents more symptoms.
Clinical Global Impression Scale (CGI-S)
Time frame: Week 7
The CGI-S will provide a global psychopathology score for all subjects. The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. A "1" is considered normal while a "7" is extremely ill.

2 secondary outcomes

Peripheral Biomarkers of Inflammation
Time frame: week 7
Cortisol
Time frame: 7 weeks

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2026.
Derived from this study: PubMed 38037108Dixon T, Cadenhead KS. Cannabidiol versus placebo as adjunctive treatment in early psychosis: study protocol for randomized controlled trial. Trials. 2023 Nov 30;24(1):775. doi: 10.1186/s13063-023-07789-w.
Individual participant dataSharing planned: No

Related trials for Early Psychosis

Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Kristin Cadenhead contact

619-543-6445

KCADENHEAD@UCSD.EDU

Kristin Cadenhead, MD principal investigator

University of California, San Diego

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cannabidiol oral solution in people with Early Psychosis, run by University of California, San Diego at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 8 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Kristin Cadenhead (619-543-6445, KCADENHEAD@UCSD.EDU), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Positive and Negative Symptoms of Psychosis (time frame: Week 7). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04411225, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jan 2026.