Cannabidiol for Treatment of Non-affective Psychosis and Cannabis Use

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.

Study Overview

• Status: Recruiting
• Conditions: Dual Diagnosis
• Intervention / Treatment: Drug: Cannabidiol; Drug: Risperidone

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 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.

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Lone Baandrup, MD, PhD; Phone Number: 0045 30270879; Email: lone.baandrup@regionh.dk

Study Locations

• Denmark
  • Glostrup, Denmark, 2600
    • Recruiting
    • Center for Neuropsychiatric Schizophrenia Research
    • Contact: Jesper Ø Rasmussen, MD; Phone Number: 0045 21576336; Email: jesper.oestrup.rasmussen@regionh.dk
    • Contact: Lone Baandrup, Med.Sc.D; Phone Number: 0045 91165903; Email: lone.baandrup@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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 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
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

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Lone Baandrup
• Collaborators: University of Copenhagen; Glostrup University Hospital, Copenhagen; Danish Center for Sleep Medicine; Copenhagen University Hospital, Denmark
• Investigators: Principal Investigator: Lone Baandrup, MD, PhD, Mental Health Services Capital Region in Denmark

Publications and helpful links

General Publications

• Rasmussen JO, Jennum P, Linnet K, Glenthoj BY, Baandrup L. Cannabidiol versus risperidone for treatment of recent-onset psychosis with comorbid cannabis use: study protocol for a randomized controlled clinical trial. BMC Psychiatry. 2021 Aug 14;21(1):404. doi: 10.1186/s12888-021-03395-9.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: September 22, 2019
• First Submitted That Met QC Criteria: September 24, 2019
• First Posted (Actual): September 26, 2019

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: psychosis; clinical trial; cannabis
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Substance-Related Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Psychotic Disorders; Mental Disorders; Marijuana Abuse; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Dopamine Agents; Serotonin Antagonists; Dopamine Antagonists; Anticonvulsants; Risperidone; Cannabidiol
• Other Study ID Numbers: CBD-P; 2018-004893-84 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data will be available. In addition, the study protocol will be available. Data will be available after publication of planned primary and secondary analyses. There will be no end date for availability of data. Individual participant data will be available for meta-analysis. Proposals should be directed to: lone.baandrup@regionh.dk. To gain access, data requestors will need to sign a data access agreement.
• IPD Sharing Time Frame: Data will be available after publication of planned primary and secondary analyses. No end date.
• IPD Sharing Access Criteria: Proposals should be directed to: lone.baandrup@regionh.dk. To gain access, data requestors will need to sign a data access agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No