Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT04105231

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Dual Diagnosis Chemically-Induced Disorders Marijuana Abuse Mental Disorders Psychotic Disorders Schizophrenia Spectrum and Other Psychotic Disorders Substance-Related Disorders

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Center for Neuropsychiatric Schizophrenia Research

Glostrup Municipality, 2600, Denmark

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Cannabidiol

Drug

Cannabidiol oral suspension

Other names: Epidiolex

Risperidone

Drug

Risperidone, encapsulated tablet.

Other names: Risperidon

Primary outcomes

  1. 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 outcomes

  1. 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

  2. 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

  3. Amount of cannabis use per day, self-reported, since last study visit.

    Time frame: 7 weeks follow-up

    PSYSCAN cannabis questionnaire# 6-8

  4. Response

    Time frame: 7 weeks follow-up

    Response defined by PANSS total 25 percentile changes

  5. 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.

  6. 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').

  7. Psychosocial functioning

    Time frame: 7 weeks follow-up

    Personal and Social Performance Scale (PSP). Higher is better, range 1-100.

  8. Neurocognitive functioning

    Time frame: 7 weeks follow-up

    Brief Assessment of Cognition in Schizophrenia (BACS). Neurocognitive Test Battery. One composite score and six subscales.

  9. Subjective well-being

    Time frame: 7 weeks follow-up

    Subjective Well-being under Neuroleptics Scale (SWN). A measure of health-related quality of life.

  10. Circadian rest-activity cycle

    Time frame: 7 weeks follow-up

    Actigraphy. A wrist-worne device that measures kinetic energy.

  11. Subjective sleep quality

    Time frame: 7 weeks follow-up

    Pittsburgh Sleep Quality Index (PSQI). One total score, seven subscales.

  12. Objective sleep evaluation

    Time frame: 7 weeks follow-up

    Polysomnography (PSG). A measure of objective sleep variables

  13. Metabolomics

    Time frame: 7 weeks follow-up

    Markers for cannabinoids, dopamine and serotonin and their precursors and metabolites in the blood

Other outcomes

  1. Adverse events (AEs), discontinuation due to AEs, and serious adverse events (SAEs)

    Time frame: From baseline to 2 weeks after end of treatment

    Self-report

  2. Extrapyramidal and other side effects

    Time frame: 7 weeks follow-up

    Udvalget for Kliniske Undersoegelser (UKU) short version A clinician-rated scale to assess antipsychotic side effects

Sponsors and collaborators

Lead sponsor

Lone Baandrup

Other

Collaborators

  • Copenhagen University Hospital, Denmark
  • Danish Center for Sleep Medicine
  • Glostrup University Hospital, Copenhagen
  • University of Copenhagen

Registry information

Important dates

Study start
2021
Primary completion
2025
Study completion
2026
First posted
Sep 26, 2019
Registry last updated
Jan 27, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.