Protocol for Cancloz: multicentre randomised, placebo-controlled, double-blind, parallel-group adaptive trial of cannabidiol for clozapine-resistant schizophrenia
Faculty of Medicine, The University of Queensland, Woolloongabba, Australia; Metro South Addiction and Mental Health Services, Woolloongabba, Australia; Queensland Centre for Mental Health Research, Wacol, Australia; and Queensland Brain Institute, The University of Queensland, Brisbane, Australia
Queensland Centre for Mental Health Research, Wacol, Australia; Queensland Brain Institute, The University of Queensland, Brisbane, Australia; Institute for Urban Indigenous Health, Windsor, Australia; and School of Medicine and Dentistry, Griffith University, Southport, Australia
Faculty of Medicine, The University of Queensland, Woolloongabba, Australia; Metro South Addiction and Mental Health Services, Woolloongabba, Australia; and Queensland Centre for Mental Health Research, Wacol, Australia
Anastasia Suraev
Lambert Initiative for Cannabinoid Therapeutics, University of Sydney, Sydney, Australia
Iain McGregor
Lambert Initiative for Cannabinoid Therapeutics, University of Sydney, Sydney, Australia
Faculty of Medicine, The University of Queensland, Woolloongabba, Australia; and Metro South Addiction and Mental Health Services, Woolloongabba, Australia
Veronica De Monte
Metro South Addiction and Mental Health Services, Woolloongabba, Australia
Faculty of Medicine, The University of Queensland, Woolloongabba, Australia; and Queensland Centre for Mental Health Research, Wacol, Australia
Manju Shine
Metro South Addiction and Mental Health Services, Woolloongabba, Australia
Vikas Moudgil
Metro North Mental Health, Royal Brisbane Women's Hospital, Herston, Australia
Gail Robinson
Metro North Mental Health, The Prince Charles Hospital, Chermside, Australia
Stephen Parker
Faculty of Medicine, The University of Queensland, Woolloongabba, Australia; School of Medicine and Dentistry, Griffith University, Southport, Australia; and Metro North Mental Health, Royal Brisbane Women's Hospital, Herston, Australia
Ravikumar Krishnaiah
Community Mental Health, Gold Coast University Hospital, Southport, Australia
Terry Stedman
West Moreton Division of Mental Health and Specialised Services, Wacol, Australia
Allan Drummond
Goodna Community Mental Health, Goodna, Australia; and Integrated Mental Health Centre, Ipswich, Australia
Sarah Medland
QIMR Berghofer Medical Research Institute, Herston, Australia
Ravi Iyer
MAGNET: Mental Health Australia General Clinical Trials Network, Geelong, Australia; and Swinburne University of Technology, Hawthorn, Australia
Andrea Baker
Queensland Centre for Mental Health Research, Wacol, Australia
Background Although clozapine is the most effective antipsychotic for people with treatment-resistant schizophrenia (TRS), only 40% of people with TRS respond, and there is limited evidence for augmentation agents. Cannabidiol (CBD) reduces positive symptoms in individuals with schizophrenia, but no trials have specifically examined its efficacy in those with clozapine-resistant schizophrenia. Aims To examine the clinical efficacy of CBD augmentation in people with clozapine-resistant schizophrenia. Method This is a 12-week randomised, placebo-controlled, double-blind, parallel-group trial (registration number: ACTRN12622001112752). We will recruit 88 individuals with clozapine-resistant schizophrenia, randomised (1:1) to 1000 mg daily CBD versus placebo. Eligible individuals will be aged between 18 and 64 years, fulfil DSM-IV criteria for schizophrenia or schizoaffective disorder, have a total PANSS (Positive and Negative Syndrome Scale) score ≥60, have received oral clozapine for at least 18 weeks and have a clozapine level of >350 ng/mL. Interim analyses will be conducted at 25, 50 and 75% recruitment; these will also provide an opportunity to reallocate participants dependent on conditional power. The primary endpoint will be the difference in PANSS positive scores at the end of week 12. Secondary endpoints include depression, anxiety, sleep, quality of life, alcohol consumption, change in weight and metabolic syndrome components, and neurocognitive measures, as well as safety and tolerability. Discussion Novel treatments for clozapine-resistant schizophrenia are urgently needed. If found to be effective, CBD may have a role as a novel and safe adjunct to clozapine.
