Cannabidiol for Treatment of Non-affective Psychosis and Cannabis Use

Overview

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 Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: December 2024

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.

Interventions

  • Drug: Cannabidiol
    • Cannabidiol oral suspension
  • Drug: Risperidone
    • Risperidone, encapsulated tablet.

Arms, Groups and Cohorts

  • 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.
  • 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

Clinical Trial Outcome Measures

Primary Measures

  • Psychotic symptoms
    • Time Frame: 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 Measures

  • Cannabis cessation (no use of cannabis within the past two weeks) (for current cannabis users at baseline)
    • Time Frame: 7 weeks follow-up
    • Timeline follow back method
  • Cannabis use by self-reported days of cannabis use per week, since last study visit.
    • Time Frame: 7 weeks follow-up
    • Timeline follow back method
  • Amount of cannabis use per day, self-reported, since last study visit.
    • Time Frame: 7 weeks follow-up
    • PSYSCAN cannabis questionnaire# 6-8
  • Response
    • Time Frame: 7 weeks follow-up
    • Response defined by PANSS total 25 percentile changes
  • Remission
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 7 weeks follow-up
    • Personal and Social Performance Scale (PSP). Higher is better, range 1-100.
  • Neurocognitive functioning
    • Time Frame: 7 weeks follow-up
    • Brief Assessment of Cognition in Schizophrenia (BACS). Neurocognitive Test Battery. One composite score and six subscales.
  • Subjective well-being
    • Time Frame: 7 weeks follow-up
    • Subjective Well-being under Neuroleptics Scale (SWN). A measure of health-related quality of life.
  • Circadian rest-activity cycle
    • Time Frame: 7 weeks follow-up
    • Actigraphy. A wrist-worne device that measures kinetic energy.
  • Subjective sleep quality
    • Time Frame: 7 weeks follow-up
    • Pittsburgh Sleep Quality Index (PSQI). One total score, seven subscales.
  • Objective sleep evaluation
    • Time Frame: 7 weeks follow-up
    • Polysomnography (PSG). A measure of objective sleep variables
  • Metabolomics
    • Time Frame: 7 weeks follow-up
    • Markers for cannabinoids, dopamine and serotonin and their precursors and metabolites in the blood

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 45 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Lone Baandrup
  • Collaborator
    • Danish Center for Sleep Medicine
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Lone Baandrup, Head of Clinic – University of Copenhagen
  • Overall Official(s)
    • Lone Baandrup, MD, PhD, Principal Investigator, Mental Health Services Capital Region in Denmark
  • Overall Contact(s)
    • Lone Baandrup, MD, PhD, 30270879, lone.baandrup@regionh.dk

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.