Cannabidiol for Treatment of Recent-onset Psychosis With Comorbid Cannabis Use

Sponsor

Lone Baandrup (Other)

Overall Status

Recruiting

CT.gov ID

NCT04105231

Collaborator

Danish Center for Sleep Medicine (Other), Copenhagen University Hospital, Denmark (Other), Glostrup University Hospital, Copenhagen (Other), University of Copenhagen (Other)

130

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial examines the efficacy of cannabidiol (CBD) versus risperidone for treatment of psychosis and cessation of cannabis use in patients with recent-onset psychosis and comorbid cannabis use.

Condition or Disease	Intervention/Treatment	Phase
Dual Diagnosis	Drug: Cannabidiol Drug: Risperidone	Phase 2

Detailed Description

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 comorbid cannabis use. We hypothesize that CBD will ameliorate psychotic symptoms and increase the probability of cannabis cessation 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

130 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Cannabidiol for Treatment of Recent-onset Psychosis With Comorbid Cannabis Use

Actual Study Start Date :

Jun 1, 2021

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cannabidiol 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 Cannabidiol oral suspension Other Names: Epidiolex
Active Comparator: Risperidone 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 Risperidone, encapsulated tablet. Other Names: Risperidon

Arm

Intervention/Treatment

Experimental: Cannabidiol

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

Cannabidiol oral suspension

Other Names:

Epidiolex

Active Comparator: Risperidone

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

Risperidone, encapsulated tablet.

Other Names:

Risperidon

Outcome Measures

Primary Outcome Measures

Cannabis cessation (no use of cannabis within the past two weeks) [7 weeks follow-up]
Self-report (yes or no)
Psychotic symptoms [7 weeks follow-up]
Positive and Negative Syndrome Scale (PANSS) positive subscale, range 7-49. A measure of symptom severity. Higher values are worse.

Secondary Outcome Measures

Cannabis use by self-reported days of cannabis use per week, since last study visit. [7 weeks follow-up]
Timeline follow back method
Amount of cannabis use per day, self-reported, since last study visit. [7 weeks follow-up]
PSYSCAN cannabis questionnaire# 6-8
Response [7 weeks follow-up]
Response defined by PANSS total 25 percentile changes
Remission [7 weeks follow-up]
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.
Global illness severity [7 weeks follow-up]
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').
Psychosocial functioning [7 weeks follow-up]
Personal and Social Performance Scale (PSP). Higher is better, range 1-100.
Neurocognitive functioning [7 weeks follow-up]
Brief Assessment of Cognition in Schizophrenia (BACS). Neurocognitive Test Battery. One composite score and six subscales.
Subjective well-being [7 weeks follow-up]
Subjective Well-being under Neuroleptics Scale (SWN). A measure of health-related quality of life.
Circadian rest-activity cycle [7 weeks follow-up]
Actigraphy. A wrist-worne device that measures kinetic energy.
Subjective sleep quality [7 weeks follow-up]
Pittsburgh Sleep Quality Index (PSQI). One total score, seven subscales.
Objective sleep evaluation [7 weeks follow-up]
Polysomnography (PSG). A measure of objective sleep variables
Metabolomics [7 weeks follow-up]
Markers for cannabinoids, dopamine and serotonin and their precursors and metabolites in the blood

Other Outcome Measures

Adverse events (AEs), discontinuation due to AEs, and serious adverse events (SAEs) [From baseline to 2 weeks after end of treatment]
Self-report
Extrapyramidal and other side effects [7 weeks follow-up]
Udvalget for Kliniske Undersoegelser (UKU) short version A clinician-rated scale to assess antipsychotic side effects

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 non-organic psychotic disorder (DF28/DF29), or cannabis induced psychotic disorder (DF12.5)
Within the first 5 years after first episode psychosis
PANSS ≥ 60 and score of ≥ 4 on ≥ 2 PANSS-Positive subscale items: Delusions (P1), conceptual disorganization (P2), hallucinatory behaviour (P3), grandiosity (P5), suspiciousness (P6)
Regular use of cannabis at least on a weekly basis during the last 3 months
Age 18-64 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 3 months
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