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

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

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.

Study Overview

• Status: Terminated
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Cannabidiol; Drug: Placebo Olanzapine; Drug: Olanzapine; Drug: Placebo Cannabidiol

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Glostrup, Denmark, 2600
    • Psychiatric Centre Glostrup
• Germany
  • BW
    • Heidelberg, BW, Germany, 68115
      • Department of General Psychiatry, Heidelberg University
    • Mannheim, BW, Germany, 68159
      • Dep. of Psychiatry and Psychotherapy, Central Institute of Mental Health
  • BY
    • Munich, BY, Germany, 80336
      • Dept. of Psychiatry and Psychotherapy, Ludwig-Maximillians-University Munich
    • Munich, BY, Germany, 81675
      • Dept. of Psychiatry and Psychotherapy, Technical University Munich
  • ST
    • Halle, ST, Germany, 06112
      • Dept. of Psychiatry and Psychotherapy, Martin-Luther-University, Halle/Wittenberg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Central Institute of Mental Health, Mannheim
• Collaborators: Ludwig-Maximilians - University of Munich; Heidelberg University; Technical University of Munich; Glostrup University Hospital, Copenhagen; Martin-Luther-Universität Halle-Wittenberg
• Investigators: Principal Investigator: F. Markus Leweke, MD, Central Institute of Mental Health

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2015
• Primary Completion (Actual): September 16, 2024
• Study Completion (Actual): September 16, 2024

Study Registration Dates

• First Submitted: March 12, 2014
• First Submitted That Met QC Criteria: March 13, 2014
• First Posted (Estimated): March 14, 2014

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Schizophrenia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Central Nervous System Depressants; Neurotransmitter Agents; Membrane Transport Modulators; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Anticonvulsants; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Antipsychotic Agents; Olanzapine; Cannabidiol
• Other Study ID Numbers: CBD-FEP; 2012-004335-23 (EudraCT Number)