Cannabidiol versus risperidone as monotherapy for cannabis-related psychosis: a randomised double-blind clinical trial (CANRISE)

Antipsychotic treatment in psychosis is frequently limited by adverse effects that undermine adherence and increase the risk of relapse, a challenge that is particularly pronounced in patients with comorbid cannabis use, who often experience poorer outcomes and have few evidence-based treatment options. Cannabidiol (CBD), with a distinct non-dopaminergic mechanism and a favourable tolerability profile, has therefore emerged as a potential alternative. In a randomised, double-blind, active comparator trial, 64 patients with psychosis and lifetime cannabis use were assigned to treatment with CBD (300 mg twice daily) or risperidone (2 mg twice daily) for seven weeks. CBD was associated with a similar magnitude of reduction in psychotic symptoms as risperidone on the PANSS positive subscale, with no meaningful differences across secondary outcomes including treatment response, cognition, social functioning, and cannabis use. Clear differences, however, emerged in safety and tolerability: CBD was associated with fewer adverse events, fewer extrapyramidal symptoms, and fewer sexual side effects, whereas risperidone was linked to weight gain and prolactin elevation. Importantly, adherence - objectively verified through plasma drug levels - was markedly higher in the CBD group. During the lecture, Lone Baandrup will present these findings and discuss their implications for clinical psychopharmacology, highlighting the potential of CBD to support a more tolerable and adherence-oriented treatment strategy in patients with psychosis and comorbid cannabis use.