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

NCT04411225 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: 649467 CMCR Grants ProgramCadenhead
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Early Psychosis

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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.

  Week 7

Secondary Outcomes (2)

• Peripheral Biomarkers of Inflammation

  week 7

• Cortisol

  7 weeks

Other Outcomes (5)

• Eating Behavior

  7 weeks

• Body Mass Index

  7 weeks

• Cholesterol

  Baseline and week 7

Study Arms (2)

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.

Drug: Cannabidiol oral solution

Placebo Augmentation

PLACEBO COMPARATOR

Placebo will appear identical to the cannabidiol solution

Drug: Cannabidiol oral solution

Interventions

Cannabidiol oral solution DRUG

Both the active drug (cannabidiol) and placebo will be in oral solution.

Also known as: Placebo

Cannabidiol Augmentation; Placebo Augmentation

Eligibility Criteria

• Age: 16 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead
• Center for Medicinal Cannabis Research: collaborator

Study Sites (2)

UC San Diego

La Jolla, California, 92093, United States

RECRUITING

University of California, San Diego

San Diego, California, 92093, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 38037108 DERIVED

MeSH Terms

Conditions

Psychotic Disorders

Interventions

Cannabidiol

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cannabinoids; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Kristin Cadenhead, MD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristin Cadenhead

CONTACT

619-543-6445; KCADENHEAD@UCSD.EDU

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Randomization will be assigned by study statisticians.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This is a between-group, double blind, placebo controlled design.

Study Record Dates

• First Submitted: April 24, 2020
• First Posted: June 2, 2020
• Study Start: June 1, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)