Cannabidiol for Treatment of Non-affective Psychosis and Cannabis Use

Study Overview
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Brief Summary
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This trial examines the efficacy of cannabidiol (CBD) versus risperidone for treatment of psychosis in patients with non affective-psychosis and lifetime use of cannabis.

Detailed Description
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People with psychosis and comorbid cannabis use are particularly difficult to treat because cannabis use worsens psychotic symptoms and increases the risk that a first-episode psychosis will progress to schizophrenia. It is the THC (tetrahydrocannabinol) content in cannabis that aggravates psychotic symptoms whereas the CBD content has potential therapeutic effects. This trial investigates treatment with CBD (without THC) versus risperidone (an antipsychotic agent) in people with psychosis and lifetime use of cannabis. We hypothesize that CBD will ameliorate psychotic symptoms and reduce the frequency of cannabis use to a larger extent than risperidone. Sleep disturbances are often a limiting factor in the treatment of psychosis, and it is also examined how CBD affects objective and subjective sleep quality as well as circadian rest-activity cycles. Based on previous studies investigating CBD as monotherapy in patients with schizophrenia, it is expected that CBD will be associated with fewer adverse events than risperidone.

Official Title
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Cannabidiol for Treatment of Non-affective Psychosis and Cannabis Use

Conditions
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Dual Diagnosis

Intervention / Treatment
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* Drug: Cannabidiol
* Drug: Risperidone


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: ICD-10 diagnosis of schizophrenia (DF20.X), paranoid psychosis (DF22.X), acute/intermittent psychotic disorder (DF23.X), schizoaffective psychosis (DF25.X), other/not specified nonorganic psychotic disorder (DF28/DF29), or cannabis induced psychotic disorder (DF12.5) PANSS ≥ 60 and score of ≥ 4 on ≥ 2 PANSS-Positive subscale items: Delusions (P1), conceptual disorganization (P2), hallucinatory behaviour (P3), grandiosity (P5), suspiciousness (P6) Lifetime cannabis use Age 18-45 years Female patients of childbearing potential need to utilize a proper method of contraception Exclusion criteria: Treatment resistance as defined by treatment (ever) with clozapine Dependence syndrome of alcohol or psychoactive substances other than cannabis (DF1X.2 other than DF12.2) Psychotic disorder induced by alcohol or psychoactive substances other than cannabis (DF1X.5 other than DF12.5) Treatment with a long-acting injectable antipsychotic within the past month (or corresponding to the usual interval between two injections) Treatment with an oral antipsychotic within the past 7 days Use of self-administered CBD products during the trial Patients involuntarily admitted Pregnancy or lactation Severe physical illness that might influence the ability to comply with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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 (Epidiolex®) (oral suspension)100 mg/ml dosed as 3 ml in the morning for 4 days, then increased to 3 ml in the morning and 3 ml in the evening, equivalent to CBD 300 mg BID, with a total treatment duration of 7 weeks. AND Risperione placebo, encapsulated tablet. | Drug: Cannabidiol<br>* Cannabidiol oral suspension<br>* Other names: Epidiolex;|
| Active Comparator: Risperidone<br>Risperidone (encapsulated tablet) dosed as 2 mg in the morning for 4 days, then increased with 2 mg in the morning and 2 mg in the evening, with a total treatment duration of 7 weeks AND Cannabidiol placebo, oral suspension | Drug: Risperidone<br>* Risperidone, encapsulated tablet.<br>* Other names: Risperidon;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychotic symptoms | Positive and Negative Syndrome Scale (PANSS) positive subscale, range 7-49. A measure of symptom severity. Higher values are worse. | 7 weeks follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cannabis cessation (no use of cannabis within the past two weeks) (for current cannabis users at baseline) | Timeline follow back method | 7 weeks follow-up | 
| Cannabis use by self-reported days of cannabis use per week, since last study visit. | Timeline follow back method | 7 weeks follow-up | 
| Amount of cannabis use per day, self-reported, since last study visit. | PSYSCAN cannabis questionnaire# 6-8 | 7 weeks follow-up | 
| Response | Response defined by PANSS total 25 percentile changes | 7 weeks follow-up | 
| Remission | Symptomatic remission is defined according to the Andreasen et al remission criteria. The criteria define symptomatic remission as a rating of no more than mild in four core positive and four core negative symptoms on the Positive and Negative Syndrome Scale (P1, P2 P3, N1, N4, N6, G5, G9,) that is sustained for ≥6 months. Because of the duration of this study, the requirement of 6 month will not be considered. | 7 weeks follow-up | 
| Global illness severity | Global illness severity is assessed with the Clinical Global Impression Scale (CGI). We will use the severity (CGI-S) at baseline and improvement (CGI-I) scores of the CGI at the following visits. Response will be defined as much improved or better on the CGI-I. The main item 'severity of illness' is measured on a 7-point Likert scale (from 1 'normal, not at all ill' to 7 'among the most extremely ill patients'). | 7 weeks follow-up | 
| Psychosocial functioning | Personal and Social Performance Scale (PSP). Higher is better, range 1-100. | 7 weeks follow-up | 
| Neurocognitive functioning | Brief Assessment of Cognition in Schizophrenia (BACS). Neurocognitive Test Battery. One composite score and six subscales. | 7 weeks follow-up | 
| Subjective well-being | Subjective Well-being under Neuroleptics Scale (SWN). A measure of health-related quality of life. | 7 weeks follow-up | 
| Circadian rest-activity cycle | Actigraphy. A wrist-worne device that measures kinetic energy. | 7 weeks follow-up | 
| Subjective sleep quality | Pittsburgh Sleep Quality Index (PSQI). One total score, seven subscales. | 7 weeks follow-up | 
| Objective sleep evaluation | Polysomnography (PSG). A measure of objective sleep variables | 7 weeks follow-up | 
| Metabolomics | Markers for cannabinoids, dopamine and serotonin and their precursors and metabolites in the blood | 7 weeks follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psychosis, cannabis, clinical trial