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

June 4, 2021 updated by: Kristin Cadenhead, M.D., University of California, San Diego

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Anticipated)

120

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • California
      • La Jolla, California, United States, 92093
      • San Diego, California, United States, 92093
        • Recruiting
        • University of California, San Diego
        • Contact:
        • Principal Investigator:
          • Kristin S Cadenhead, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 30 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Concomitant medical or neurological illness;
  • Significant head injury;
  • Current substance abuse or positive toxicology screen for drugs including THC and CBD as detected by urine and blood samples.
  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cannabidiol Augmentation
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.
Both the active drug (cannabidiol) and placebo will be in oral solution.
Other Names:
  • Placebo
Placebo Comparator: Placebo Augmentation
Placebo will appear identical to the cannabidiol solution
Both the active drug (cannabidiol) and placebo will be in oral solution.
Other Names:
  • Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Week 7
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.
week 7
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.
Week 7
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.
week 7
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.
Week 7

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Peripheral Biomarkers of Inflammation
Time Frame: week 7

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

week 7
Cortisol
Time Frame: 7 weeks
AM Salivary Cortisol is normally in the range of 100-750 ng/dL. Higher levels are thought to represent a greater stress response.
7 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Eating Behavior
Time Frame: 7 weeks
Three Factor Eating Questionnaire will be used to query about eating behavior in different categories using total score: cognitive dietary restraint, disinhibition, and susceptibility to hunger. Each score is converted to a scaled score from 0 to 100 with the higher score representing more restraint, more dishinibition and less hunger.
7 weeks
Body Mass Index
Time Frame: 7 weeks
Height and weight will be used to calculate Body Mass Index, a ratio of height and weight. Normal BMI is considered 18.5 to 25.
7 weeks
Cholesterol
Time Frame: Baseline and week 7
serum will be drawn to measure total cholesterol, low density and high density lipoproteins along with Triglycerides. All are measured in mg/dL. Normal values include Total Cholesterol <=199, Triglycerides 30 - 149, High Density Lipoprotein 40-59, Low Density Lipoprotein <=129.
Baseline and week 7
Electrophysiology Mismatch Negativity
Time Frame: Baseline and week 7
Mismatch Negativity (MMN) measured in an event related potential paradigm. The value is expressed in micorvolts and represents the difference in response to standard versus mismatch stimuli measure at 100 milliseconds post stimuli. The mismatch negativity value varies between 0 and -6 microvolts with greater negative numbers representing greater mismatch negativity. The MMN is thought primarily to reflect the activity of sensory memory, with, at most, moderate influences of higher-level cognitive processes, such as attention.
Baseline and week 7
Electrophysiology - Prepulse Inhibition
Time Frame: Baseline and week 7
Prepulse Inhibition of the human startle response. Prepulse Inhibition is expressed as a percentage from 0 to 100 with the higher value presenting greater inhibition.
Baseline and week 7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Kristin Cadenhead, MD, University of California, San Diego

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

July 1, 2021

Primary Completion (Anticipated)

June 30, 2023

Study Completion (Anticipated)

June 30, 2023

Study Registration Dates

First Submitted

April 24, 2020

First Submitted That Met QC Criteria

May 27, 2020

First Posted (Actual)

June 2, 2020

Study Record Updates

Last Update Posted (Actual)

June 9, 2021

Last Update Submitted That Met QC Criteria

June 4, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Other Study ID Numbers

  • 649467 CMCR Grants Program
  • Cadenhead (Other Grant/Funding Number: Krupp Endowed Fund)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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