A Four-week Clinical Trial Investigating Efficacy and Safety of Cannabidiol as a Treatment for Acutely Ill Schizophrenic Patients

Study Overview
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Brief Summary
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Schizophrenia is a heterogeneous mental disorder that affects one percent of the world's population. Current antipsychotics are only partially effective, and their use is often associated with serious side effects. Cannabidiol is a natural counterpart of the psychoactive component of marijuana, delta-9-tetrahydrocannabinol. While cannabidiol has no psychotomimetic or addictive properties, it indirectly affects endogenous cannabinoid signalling by impairing the degradation of the endocannabinoid anandamide. In a controlled clinical trial of cannabidiol versus amisulpride (an established antipsychotic) in acute paranoid schizophrenics the investigators showed a significant clinical improvement in all symptoms of schizophrenia compared to baseline with either treatment. But cannabidiol displayed a significantly superior side-effect profile. This study is to evaluate the efficacy and safety of this novel treatment option in comparison to placebo and olanzapine, an established second generation antipsychotic in the treatment of acute schizophrenia and schizophrenia maintenance therapy, in a four-week clinical trial.

Official Title
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A Four-week, Multicentre, Double-blinded, Randomised, Active- and Placebo- Controlled, Parallel-group Trial Investigating Efficacy and Safety of Cannabidiol in Acute, Early-stage Schizophrenic Patients

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Cannabidiol
* Drug: Olanzapine
* Drug: Placebo Cannabidiol
* Drug: Placebo Olanzapine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent given by the subject DSM-IV-TR diagnosis of schizophrenic psychosis (295.10, 295.20, 295.30, 295.90 (American Psychiatric Association) Patients must be within the first three years of illness, i.e. first diagnosis of schizophrenia is no older than three years. Age 18 to 65 years, male or female Minimal initial PANSS score of 75 at baseline Female patients of childbearing potential need to utilize a proper method of contraception. Body Mass Index between 18 and 40 Exclusion Criteria: Lack of accountability (assessed by an independent psychiatrist) History of treatment-resistant schizophrenia, defined as no response to at least two antipsychotics given for a minimum of 6 weeks each in an adequate dosage Positive urine drug-screening for illicit drugs at screening (except cannabinoids and benzodiazepines) Serious suicidal risk at screening visit (Subject to investigator's and independent psychiatrist's judgement: Poses a serious suicidal or homicidal risk at screening visit or has made a serious suicide attempt within the last 12 months prior to screening visit, or has exhibited homicidal behaviour at anytime during her/his lifetime) Known intolerance or allergy to olanzapine or cannabidiol Other relevant interferences of axis 1 (e.g. serious depression) according to diagnostic evaluation (MINI) including residual forms of schizophrenia Pregnancy, as determined through a β-HCG pregnancy test, or lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cannabidiol<br>Cannabidiol capsules 2x200 mg twice a day and placebo olanzapine capsule once a day over 4 weeks | Drug: Cannabidiol<br>* Cannabidiol capsules<br>Drug: Placebo Olanzapine<br>* Placebo olanzapine capsules<br>|
| Active Comparator: Olanzapine<br>Olanzapine capsule 15mg once a day and placebo cannabidiol capsules twice a day over 4 weeks | Drug: Olanzapine<br>* Olanzapine capsules<br>* Other names: Olanzapine 1A pharma;Drug: Placebo Cannabidiol<br>* Placebo cannabidiol capsules<br>|
| Placebo Comparator: Placebo<br>Placebo cannabidiol capsules twice a day and placebo olanzapine capsule once a day over 4 weeks | Drug: Placebo Cannabidiol<br>* Placebo cannabidiol capsules<br>Drug: Placebo Olanzapine<br>* Placebo olanzapine capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Positive and Negative Syndrome Scale (PANSS) total score |  | within 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the PANSS subscores and clusters |  | within 4 weeks | 
| Changes in the Clinical Global Impression score |  | within 4 weeks | 
| Changes in the Global Assessment of Functioning Scale |  | within 4 weeks | 
| Changes in the Personal and Social Performance Scale |  | within 4 weeks | 
| Changes in the Calgary Depression Scale for Schizophrenia |  | within 4 weeks | 
| Changes in the Hamilton Anxiety Scale |  | within 4 weeks | 
| Changes in cognitive skills |  | within 4 weeks | 
| Response to antipsychotic medication |  | within 4 weeks | 
| Plasma levels of endogenous cannabinoids |  | within 4 weeks | 
| Changes in physiological parameter |  | within 4 weeks | 
| Changes in the UKU Side Effect Rating Scale |  | within 4 weeks | 
| Columbia Suicidality Severity Rating Scale |  | within 4 weeks |