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

INTERVENTION: Product Name: Cannabidiol (enhanced formulation) Product Code: CBD CR Pharmaceutical Form: Tablet INN or Proposed INN: Cannabidiol CAS Number: 13956‐29‐1 Other descriptive name: CANNABIDIOL Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 20‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use Trade Name: Olanzapin 1‐A Pharma Filmtabletten Product Name: Olanzapine Pharmaceutical Form: Capsule, hard INN or Proposed INN: OLANZAPINE CAS Number: 132539‐06‐1 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 15‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Product Name: Cannabidiol (enhanced formulation) Product Code: CBD CR Pharmaceutical Form: Tablet CAS Number: 13956‐29‐1 Other descriptive name: CANNABIDIOL Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 150‐ Pharmaceutical form of the placebo: Tablet Route of administration of the placebo: Oral use CONDITION: Acute early‐stage psychosis ; MedDRA version: 17.0 Level: SOC Classification code 10022891 Term: Investigations System Organ Class: 10022891 ‐ Investigations ; MedDRA version: 17.0 Level: SOC Classification code 10018065 Term: General disorders and administration site conditions System Organ Class: 10018065 ‐ General disorders and administration site conditions Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] PRIMARY OUTCOME: Main Objective: Evaluation of the efficacy of cannabidiol in alleviating the positive, negative and general symptoms of schizophrenia compared to olanzapine and placebo. ; Primary end point(s): Change in the PANSS total score from baseline to week 4 of treatment Secondary Objective: Test of the efficacy and safety of cannabidiol, a potential enhancer of endocannabinoid action, in comparison to placebo and olanzapine in patients suffering from acute schizophrenia who are within the first three years of illness.; Impact of cannabidiol on metabolic functioning in comparison to placebo and olanzapine.; Quantification of the incidence of extrapyramidal unwanted effects following cannabidiol treatment in comparison to placebo and olanzapine;; Exploration of the relationship between symptom severity and plasma levels of cannabidiol and/or endocannabinoids.; Timepoint(s) of evaluation of this end point: Day 28 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 150 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range SECONDARY OUTCOME: Secondary end point(s): • Changes from baseline in the PANSS subscores and clusters; • Changes from baseline in the Clinical Global Impression score (CGI); • Proportion of responders defined as (1) at least 30 % decrease in the PANSS score and (2) score of 1 or 2 on the CGI score; • Changes from baseline in the Calgary Depression Scale for Schizo‐phrenia (CDSS); • Changes from baseline in weight, waist circumference, fasting blood glucose levels, HBA1C, HDL/LDL cholesterole, and triglyceride levels as well as prolactine levels; • Proportion of subjects considered to be in remission; •Time to readiness for hospital discharge; • Time to maintained response and time to all cause discontinuation; • Subject’s Response to Antipsychotic (SRA) medication; • Subject’s treatment satisfaction questionnaire; and Subjective Well‐Being under Neuroleptics (SWN); • Medication Adherence Rating Scale (MARS); Timepoint(s) of evaluation of this end point: Day 28