Background: Data on associations between cannabis use and psychopathology, cognition and functional impairment in schizophrenia spectrum disorders (SSD) is controversial. Objectives: To examine the effect of cannabis on psychopathology, cognition and real-world functioning in SSD patients. Method: Naturalistic cross-sectional study, 123 clinically stable SSD outpatients. Assessment: demographic and clinical data, psychometric evaluation: Positive and Negative Syndrome, Hamilton Depression Rating, Clinical Global Impression (CGI), Personal and Social Performance and Screen for Cognitive Impairment in Psychiatry (SCIP) scales. Patients were classified as cannabis user patients (CUP) and non cannabis user patients (NCUP) according to self-report, both lifetime and last year. Statistical analysis: chi-square, Student t test, ANOVA (Duncan post hoc), and general linear model analysis for adjusting for antipsychotic doses. Results: Mean age 40.75, 66.7% male, single (66.7%), prior hospital admissions 2.75, mean length of illness 13.85 years. 53.7% were lifetime cannabis users and 8.9% last year users. Lifetime CUP had more hospitalizations (p = 0.013) at a younger age (p = 0.002), and showed better cognitive functioning globally (CGI-C: p = 0.045) and on working memory and processing speed (SCIP-2: p = 0.039; SCIP-5: p = 0.033) and worse functioning in socially useful activities (p = 0.014) than NCUP. All these differences remained after adjusting for antipsychotic doses. Last year cannabis users had worse mood (Hamilton Depression Rating Scale 9.66 vs. 5.64; p = 0.002), but this difference disappears when adjusting for antipsychotic doses. Conclusions: Lifetime cannabis use is associated with better working memory and processing speed and worse real-world functioning in the area of socially useful activities in patients with schizophrenia-related disorders. Clinicians should, therefore, be aware of it to provide patient-centred care in their daily clinical practice.

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