Cariprazine in First-Episode Psychosis with Comorbid Cannabis Use: A Case Series of Eight Patients from Two Greek Early Intervention Units

Background/Objectives: Cannabis use is prevalent in first-episode psychosis (FEP) and is associated with poor clinical outcomes. Cariprazine, a dopamine D3/D2 partial agonist with preferential D3 affinity, may offer clinical advantages for both psychotic symptoms and comorbid substance use; however, naturalistic data in FEP patients with active cannabis use are lacking. Methods: We conducted a retrospective naturalistic case series of eight FEP patients with active cannabis use treated with cariprazine for six months across two Greek Early Intervention Units (PNOES Athens and Thessaloniki, EPAPSY). Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) Five-Factor (Marder) model and cannabis use using the Cannabis Experience Questionnaire (CEQ) at baseline and six months. Analyses were descriptive, with exploratory Wilcoxon signed-rank tests. Results: At six months, lower mean PANSS scores were observed for positive symptoms (12.88 vs. 9.50), disorganization (11.38 vs. 9.13) and, to a lesser degree, anxiety/depression (9.38 vs. 8.50). Negative symptoms changed little (16.13 vs. 15.00), and hostility was essentially unchanged (10.63 vs. 11.63). Only the reduction in positive symptoms reached nominal significance (p = 0.047; dz = −1.05), which did not survive correction for multiple comparisons. Cannabis-use frequency decreased in seven of eight participants, with two reporting complete cessation. Conclusions: These preliminary, hypothesis-generating observations suggest that cariprazine may warrant further study in FEP with comorbid cannabis use. The findings cannot be interpreted as evidence of efficacy given the small, uncontrolled, diagnostically heterogeneous sample.