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
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Enrollment
- 150
- Locations
- 6
- Primary Endpoint
- Change in the Positive and Negative Syndrome Scale (PANSS) total score
Study Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Cannabidiol
Cannabidiol capsules 2x200 mg twice a day and placebo olanzapine capsule once a day over 4 weeks
Intervention: Cannabidiol (Drug)
Cannabidiol
Cannabidiol capsules 2x200 mg twice a day and placebo olanzapine capsule once a day over 4 weeks
Intervention: Placebo Olanzapine (Drug)
Olanzapine
Olanzapine capsule 15mg once a day and placebo cannabidiol capsules twice a day over 4 weeks
Intervention: Olanzapine (Drug)
Olanzapine
Olanzapine capsule 15mg once a day and placebo cannabidiol capsules twice a day over 4 weeks
Intervention: Placebo Cannabidiol (Drug)
Placebo
Placebo cannabidiol capsules twice a day and placebo olanzapine capsule once a day over 4 weeks
Intervention: Placebo Cannabidiol (Drug)
Placebo
Placebo cannabidiol capsules twice a day and placebo olanzapine capsule once a day over 4 weeks
Intervention: Placebo Olanzapine (Drug)
Outcomes
Primary Outcomes
Change in the Positive and Negative Syndrome Scale (PANSS) total score
Time Frame: within 4 weeks
Secondary Outcomes
- Response to antipsychotic medication(within 4 weeks)
- Changes in physiological parameter(within 4 weeks)
- Changes in the Personal and Social Performance Scale(within 4 weeks)
- Changes in the UKU Side Effect Rating Scale(within 4 weeks)
- Changes in the Global Assessment of Functioning Scale(within 4 weeks)
- Changes in the Clinical Global Impression score(within 4 weeks)
- Changes in the Hamilton Anxiety Scale(within 4 weeks)
- Changes in cognitive skills(within 4 weeks)
- Columbia Suicidality Severity Rating Scale(within 4 weeks)
- Changes in the PANSS subscores and clusters(within 4 weeks)
- Changes in the Calgary Depression Scale for Schizophrenia(within 4 weeks)
- Plasma levels of endogenous cannabinoids(within 4 weeks)