A randomised, double-blind, placebo-controlled parallel group, pilot study of 40:1 ratio of formulated GWP42003 : GWP42004 in the treatment of iatrogenic weight gain and dyslipidaemia associated with olanzapine or other antipsychotic(s) treatment in subjects with schizophrenia or other non-affective psychosis.

INTERVENTION: Product Name: GWP42003 Capsule Product Code: EN0012 Pharmaceutical Form: Capsule, hard Current Sponsor code: GWP42003 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Product Name: GWP42004 Capsule Product Code: EN0011 Pharmaceutical Form: Capsule, hard Current Sponsor code: GWP42004 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Iatrogenic weight gain and dyslipidaemia associated with treatment using antipsychotic medication ; MedDRA version: 14.1 Level: LLT Classification code 10058110 Term: Dyslipidemia System Organ Class: 10027433 ‐ Metabolism and nutrition disorders ; MedDRA version: 14.1 Level: LLT Classification code 10047896 Term: Weight gain System Organ Class: 10022891 ‐ Investigations Therapeutic area: Diseases [C] ‐ Nutritional and Metabolic Diseases [C18] PRIMARY OUTCOME: Main Objective: To evaluate the efficacy of a 40:1 ratio of GWP42003 : GWP42004 compared with placebo in the change in body weight from baseline in subjects treated with olanzapine or other antipsychotic(s) in subjects with schizophrenia or other non‐affective psychosis. Primary end point(s): To evaluate the efficacy of a 40:1 ratio of GWP42003 : GWP42004 compared with placebo in the change in body weight from baseline in subjects treated with antipsychotic(s) for schizophrenia or other non‐affective psychosis Secondary Objective: To evaluate the efficacy of a 40:1 ratio of GWP42003 : GWP42004 compared with placebo on:; Lipid parameters; Glucose Control (fasted); Insulin Control (fasted); Glycosylated haemoglobin A1c (HbA1c); Adipose tissue distribution; Markers of adipocyte function including leptin and adiponectin; Markers of inflammation including cytokines and C‐Reactive Protein (CRP); Hormonal markers including prolactin; Endocannabinoid plasma levels; Positive symptoms of schizophrenia; Negative symptoms of schizophrenia; General symptoms of schizophrenia; Physician’s global impression of illness severity; Subject’s quality of life; Assessment of symptoms of depression; Assessment of extrapyramidal symptoms; Assessment of mood; Assessment of appetite.; To assess the safety and tolerability of a 40:1 ratio of GWP42003 : GWP42004 compared with placebo on:; Adverse events (AE); Vital Signs; Electrocardiogram (ECG); Laboratory findings; Physical examination. Timepoint(s) of evaluation of this end point: 6 weeks post treatment SECONDARY OUTCOME: Secondary end point(s): To evaluate the effect of a 40:1 ratio of GWP42003 : GWP42004 compared with placebo on: ; ; Body Fat Parameters: ; ‐ Change from baseline to end of treatment in skin fold thickness measurements; ; ‐ Change from baseline to end of treatment in waist to hip ratio; ; ; Lipid Parameters: ; ‐ Change from baseline to end of treatment in serum Total Cholesterol; ; ‐ Change from baseline to end of treatment in serum LDL Cholesterol; ; ‐ Change from baseline to end of treatment in serum HDL Cholesterol; ; ‐ Change from baseline to end of treatment in serum HDL / LDL Cholesterol ratio; ; ‐ Change from baseline to end of treatment in serum HDL / Total Cholesterol ratio; ; ‐ Change from baseline to end of treatment in serum Triglycerides; ; ‐ Change from baseline to end of treatment in serum apolipoprotein markers (ApoA & ApoB); ; ‐ Change from baseline to end of treatment in serum Apo A/Apo B ratio; ; ‐ Change from baseline to end of treatment in serum non‐esterified (“free”) fatty acids to the end of treatment; ; ; Glucose Control: ; ‐ Change from baseline to end of treatment in glucose control parameters (fasting plasma glucose); ; ‐ Change from baseline to end of treatment in HbA1c (whole blood); ; ; Insulin Control: ; ‐ Change from baseline to end of treatment in insulin control parameters (fasting serum insulin); ; ; Psychiatric/Clinical Assessments: ; Change from baseline to end of treatment in the following assessments: ; ‐ Positive and Negative Syndrome Scale (PANSS) ‘P’; ‘N’; ‘G’; ; ‐ Global Assessment of Functioning (GAF); ; ‐ Beck Depression Inventory (BDI); ; ‐ UWIST Mood Adjective Checklist (UMACL); ; ‐ Simpson‐Angus Scale (SAS); ; ‐ End of treatment assessment of Clinician’s Global Impression of Change (CGIC); ; ; Hormonal Marker: ; ‐ Change from baseline to end of treatment in serum prolactin concentration; ; ; Markers of Inflammation: ; ‐ Change from baseline to end of treatment in serum CRP and serum cytokines (including TNF‐a, IL‐6 and IL‐2); ; ; Markers of adipocyte function: ; ‐ Change from baseline to end of treatment in serum leptin and adiponectin concentrations; ; ; Endocannabinoid Levels‐ where facilities allow: ; ‐ Change from baseline in endocannabinoid plasma levels to the end of treatment; ; ; Appetite Assessments: ; ‐ Change from baseline in mean appetite NRS score (taken from the last 7 days of baseline period (days ‐7 to 0) to the end of treatment (taken from last 7 days of treatment period); ; ; Safety Endpoints: ; To assess the safety and tolerability of a 40:1 ratio of CBD : THCV compared with placebo on: ; ‐ AEs; ; ‐ Vital signs; ; ‐ ECG; ; ‐ Laboratory findings; ; ‐ Physical examination. Timepoint(s) of evaluation of this end point: 6 weeks post treatment INCLUSION CRITERIA: For inclusion in the study subjects must fulfil ALL of the following criteria: ‐ Willing and able to give informed consent for participation in the study. ‐ Subject is aged 18 years or above. ‐ Diagnosis (DSM‐IV‐TR) of schizophrenia, or other non‐affective psychosis. ‐ Receiving at least one antipsychotic. ‐ The dose of antipsychotic(s) is stable for at least 2 weeks prior to randomisation (Visit 2). ‐ Subject is willing to maintain a stable dose of antipsychotic(s) for the duration of the study. ‐ Evidence of recent weight gain attributable to antipsychotic treatment (in the opinion of the Investigator), prior to screening (Visit 1). Wherever possible, investigator must exclude other possible causes of weight gain, such as change in exercise, diet , concomitant medications or other illnesses. ‐ Each subject must have a further documented 2% weight gain attributable to antipsychotic treatment in the baseline period (between Visits