Patients with schizophrenia and cannabis use disorder showed greater reductions in craving and insula brain activity when treated with clozapine compared to risperidone.
Read this if you want to understand which antipsychotic medications may better address cannabis craving in schizophrenia.
Craving reductions correlated with decreased insula activation during cannabis cue processing
What the researchers found
In a randomized trial of 36 patients with schizophrenia and cannabis use disorder, those treated with clozapine showed larger reductions in subjective craving and decreased activation of the insula during a cannabis-word Stroop task compared to those on risperidone. The insula is a brain region involved in craving and interoceptive awareness.
Decreases in subjective craving were significantly associated with decreases in insula activation during the cannabis-related task, suggesting a shared neural mechanism. Risperidone-treated patients showed greater decreases in anterior cingulate cortex activation during a classical (non-cannabis) Stroop task.
Nineteen healthy controls were also included for baseline comparison of brain activity patterns.
Why it matters
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.
The numbers in context
36 patients with schizophrenia and 19 healthy controls participated. Measurements were taken at baseline and after 4 weeks of treatment. Clozapine reduced both craving and insula activation during cannabis-related cognitive tasks.
How the study worked
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.
What this study cannot tell us
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.
How to read the evidence
This is a randomized controlled trial with neuroimaging, but the sample size was small and the follow-up was short.
When this study was published
Published in 2014. Clozapine remains the recommended antipsychotic for treatment-resistant schizophrenia, though research on its anti-craving properties continues.
The bigger picture
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.
Questions still open
- Does the reduction in craving with clozapine translate to actual reductions in cannabis use over time? What specific pharmacological properties of clozapine drive its anti-craving effects? Would other atypical antipsychotics show similar effects?
Common questions
Why is cannabis use a particular concern in schizophrenia?
What is attentional bias?
Read the original research
The effect of clozapine and risperidone on attentional bias in patients with schizophrenia and a cannabis use disorder: An fMRI study.
Journal of psychopharmacology (Oxford, England), 28(7), 633-42
Citation
Machielsen, Marise Wj; Veltman, Dick J; van den Brink, Wim; de Haan, Lieuwe. (2014). The effect of clozapine and risperidone on attentional bias in patients with schizophrenia and a cannabis use disorder: An fMRI study.. Journal of psychopharmacology (Oxford, England), 28(7), 633-42. https://doi.org/10.1177/0269881114527357
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