¹Association for Regional Development and Mental Health (EPAPSY), Early Intervention Service PNOES SKG, Thessaloniki, Greece, ²Aristotle University of Thessaloniki, 2nd Department of Psychiatry, Thessaloniki, Greece

Background: Cannabis use is highly prevalent among individuals with First-episode psychosis (FEP). Their coincidence has been associated with an unfavorable clinical course, with greater symptom severity, elevated relapses and hospitalization rates, poorer adherence and functioning, and heightened impulsiveness. Managing psychotic symptoms while effectively managing comorbid cannabis use remains a considerable challenge in clinical practice. Cariprazine is a dopamine D3/D2 partial agonist with preferential affinity for D3 receptors and has been shown to exert beneficial effects beyond the core symptoms of psychosis. While only limited studies are available, previous findings in the literature suggest that cariprazine may also positively influence impulsivity and substance use–related behaviors, indicating a potential role in patients with psychosis and comorbid cannabis use.

Aims & Objectives: The aim of the current study was to explore whether treatment with cariprazine is associated with reductions in psychotic symptoms, impulsivity, and the frequency of cannabis use in patients experiencing a first episode of psychosis.

Method: This case series included eight patients with first-episode psychosis and ongoing cannabis use treated in early intervention services in Thessaloniki and Athens. All patients received cariprazine as part of routine clinical care (mean dose: 4.5 mg/day). One patient received also treatment with another atypical antipsychotic. Clinical data were collected through standardized rating scales; PANSS (Positive and Negative Syndrome Scale) for psychotic symptomatology and CEQ (Cannabis Experience Questionnaire) for cannabis use. Changes were evaluated over a six-month follow-up period.

Results: During the six-month follow-up period, mean PANSS total and subscale scores showed a downward trend, reflecting an overall reduction in psychotic symptom severity across the sample. Mean cannabis use frequency also decreased over time, with two of the eight patients discontinuing cannabis use during follow-up according to CEQ. Changes in impulsivity (PANSS General psychopathology variable on Poor Impulse Control- G14) were more heterogeneous, and no consistent reduction was observed at the group level. Cariprazine was generally well tolerated, and no treatment discontinuations due to adverse effects were reported.

Discussion & Conclusions: In this small case series, cariprazine was associated with a reduction in psychotic symptoms and cannabis use, with two patients stopping cannabis entirely. Changes in impulsivity were variable. These findings align with limited existing literature suggesting potential benefits of cariprazine in dual-diagnosis patients. Due to the small sample and descriptive design, results are preliminary, but they support further investigation of cariprazine for early psychosis with comorbid cannabis use.