Cannabidiol Early Psychosis Project: A Randomised Controlled Trial

Funded Activity Summary

The proposed study aims to answer an important clinical question: can subthreshold psychotic manifestations (using UHR criteria by CI Yung9) be effectively treated with cannabidiol (CBD), a non- psychoactive compound of the plant Cannabis sativa? The question has taken on increased clinical importance in the wake of recent evidence questioning the need and efficacy of specific interventions in the UHR group.10 In this study, we will test CBD for the first time in the UHR phase of psychotic disorder. Since the therapeutic action of CBD does not appear to depend on dopamine receptor antagonism,11,12 this agent may represent a new class of treatment for UHR patients when treatment with conventional antipsychotic medication is controversial and has no good evidence base. Even if prescribed early, available drugs, such as antipsychotics or antidepressants, do not seem to prevent psychosis progression or improve psychosocial functioning in individuals at UHR of psychosis,10 necessitating the development of novel treatment approaches. The favourable risk-benefit ratio and the high margin of safety of CBD coupled to recent findings in support of its efficacy in patients with schizophrenia,12 and first evidence that a single dose of CBD can normalise alterations in parahippocampal, striatal, and midbrain function associated with the UHR state,13 support this proposal. Setting: 8 recruitment sites across 4 states of Australia utilising a nationwide network of early psychosis services14 and related research network,15 including Orygen's PACE early psychosis program and its 4 linked headspace centres in Melbourne, VIC (5 recruitment sites) and headspace Youth Early Psychosis Program (hYEPP) centres in Adelaide, SA, Gold Coast, QLD, and Perth, WA (3 recruitment sites). Primary aim: To determine if CBD is an effective treatment for UHR patients. Patients and study design: Three-arm randomised controlled trial (RCT) – with a placebo arm and 2 discreet drug doses – 405 patients (135 per arm) aged 12-25 years who meet UHR for psychosis criteria. Intervention: CBD (per oral) – doses of 600 mg or 1000 mg per day (fixed schedule) for 12 weeks. Primary outcome: Improvement of positive psychotic symptoms on the Comprehensive Assessment of At-Risk Mental States (CAARMS) at 12 weeks. Secondary outcomes: Improvement of other domains of psychopathology (negative symptoms, depression and anxiety), distress associated with positive psychotic symptoms; transition to psychotic disorder; overall clinical improvement (CGI), social and occupational functioning; quality of life; safety and tolerability at 12 weeks; cost-effectiveness. A follow-up research assessment will be conducted on all participants at 6 months. Additional longer-term follow-up data will be collected within the study period (3 years recruitment and 6 months follow-up) on participants who are 1 year and 2 years post-baseline. Primary hypothesis: That CBD will be significantly more effective than placebo in improving positive psychotic symptoms in UHR patients at 12 weeks. Predictive biomarkers: Blood and urine parameters of cannabinoids; inflammatory cytokines and oxidative stress measures from plasma; hair cortisol.

Funded Activity Details

Start Date: 01-01-2020

End Date: 01-01-2025

Funding Scheme: Funding Scheme not available

Funder: WELLCOME TRUST

Research Topics

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