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

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Early Psychosis

Intervention / Treatment
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* Drug: Cannabidiol oral solution


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a between-group, double blind, placebo controlled design.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cannabidiol Augmentation<br>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<br>* Both the active drug (cannabidiol) and placebo will be in oral solution.<br>* Other names: Placebo;|
| Placebo Comparator: Placebo Augmentation<br>Placebo will appear identical to the cannabidiol solution | Drug: Cannabidiol oral solution<br>* Both the active drug (cannabidiol) and placebo will be in oral solution.<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | 7 weeks |