Clozapine Reduced Cannabis Craving More Than Risperidone in Patients with Schizophrenia

Patients with schizophrenia and cannabis use disorder were randomized to receive either clozapine or risperidone. At baseline and after 4 weeks of medication, researchers measured brain activity using fMRI during two tasks: a classical Stroop task (measuring general cognitive control) and a cannabis word Stroop task (measuring attentional bias toward cannabis-related cues). Subjective craving was also assessed at both time points.

Cannabis use disorder is highly prevalent among people with schizophrenia and worsens outcomes. This study provides neuroimaging evidence for why clozapine may be a better antipsychotic choice for this specific population, showing that it targets the brain's craving circuitry more effectively than risperidone.

Choosing the right antipsychotic for patients with co-occurring schizophrenia and substance use disorders remains challenging. This study adds neurobiological support to clinical observations that clozapine may have specific anti-craving properties, potentially through its effects on the insula and broader salience network.

The sample size was relatively small (36 patients total across two treatment groups). The study lasted only 4 weeks, so longer-term effects on craving and cannabis use were not assessed. The study did not measure actual cannabis consumption outcomes. Clozapine has significant side effects including required blood monitoring, which limits its first-line use.