Cannabidiol versus risperidone for treatment of recent-onset psychosis with comorbid cannabis use: study protocol for a randomized controlled clinical trial

Jesper Østrup Rasmussen, Poul Jennum, Kristian Linnet, Birte Y Glenthøj, Lone Baandrup, Jesper Østrup Rasmussen, Poul Jennum, Kristian Linnet, Birte Y Glenthøj, Lone Baandrup

Abstract

Background: Cannabis use is an important risk factor for development of psychosis and further transition to schizophrenia. The prevalence of patients with psychosis and comorbid cannabis use (dual diagnosis) is rising with no approved specialized pharmacological treatment option. Cannabidiol, a constituent of the Cannabis sativa plant, has potential both as an antipsychotic and as a cannabis substituting agent. The aim of this study is to evaluate the efficacy of cannabidiol versus a first-choice second-generation antipsychotic (risperidone) in patients with early psychosis and comorbid cannabis use.

Methods: The study is a phase II randomized, double-blinded, parallel-group, active-comparator clinical trial. We plan to include 130 patients aged between 18 and 64 years with a recent diagnosis of psychosis, comorbid cannabis use, and currently not treated with antipsychotics. The participants will be randomized to seven weeks of treatment with either cannabidiol 600 mg (300 mg BID) or risperidone 4 mg (2 mg BID). Participants will undergo clinical assessment after 1, 3, 5 and 7 weeks, telephone assessment the weeks in between, and a safety visit two weeks after end of treatment. The primary outcomes are cessation of cannabis use (self-reported) and psychotic symptom severity. The secondary outcomes include frequency and quantity of cannabis use, global illness severity, psychosocial functioning, subjective well-being, cognition, sleep, circadian rhythmicity, and metabolomics.

Discussion: The results of this trial can potentially contribute with a new treatment paradigm for patients suffering from dual diagnosis.

Trial registration: ClinicalTrials.gov , NCT04105231 , registered April 23rd, 2021.

Keywords: Antipsychotic medication; Cannabidiol; Cannabis; Dual diagnosis; Psychosis; Randomized clinical trial; Schizophrenia; THC.

Conflict of interest statement

Dr. Lone Baandrup is a member of BMC editorial board. Dr. Glenthøj is the leader of a Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), which is partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen, and other foundations. All grants are the property of the Mental Health Services in the Capital Region of Denmark and administrated by them. She has no other conflicts to disclose.

None of the other authors declare that they have competing interests.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Schedule of enrolment, interventions, visits and assessments. Abbreviations: AE: Adverse event. PANSS: Positive and Negative Syndrome Scale (rating scale - symptom severity). CGI: Clinical Global Impression scale (rating scale – global illness severity), Severity (S) and Improvement (I) scores. PSP: Personal and Social Performance Scale (rating scale – level of psychosocial functioning). SWN: Subjective Well-being Scale under Neuroleptic treatment (rating scale – well-being). BACS: Brief Assessment of Cognition in Schizophrenia (neuropsychiatric test battery). UKU: Udvalget for Kliniske Undersøgelser (rating scale – antipsychotic side effects). PSQI: Pittsburgh Sleep Quality Index (rating scale – subjective sleep quality)

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