BACKGROUND: The association between cannabis use and positive symptoms in schizophrenia spectrum disorders is well documented, especially via meta-analyses. Yet, findings are inconsistent regarding negative symptoms, while other dimensions such as disorganization, depression, and excitement, have not been investigated. In addition, meta-analyses use aggregated data discarding important confounding variables which is a source of bias. METHODS: PubMed, ScienceDirect and PsycINFO were used to search for publications from inception to September 27, 2022. We contacted the authors of relevant studies to extract raw datasets and perform an Individual Participant Data meta-analysis (IPDMA). Inclusion criteria were: psychopathology of individuals with schizophrenia spectrum disorders assessed by the Positive and Negative Syndrome Scale (PANSS); cannabis-users had to either have a diagnosis of cannabis use disorder or use cannabis at least twice a week. The main outcomes were the PANSS subscores extracted via the 3-factor (positive, negative and general) and 5-factor (positive, negative, disorganization, depression, excitement) structures. Preregistration is accessible via Prospero: ID CRD42022329172. FINDINGS: Among the 1149 identified studies, 65 were eligible and 21 datasets were shared, totaling 3677 IPD and 3053 complete cases. The adjusted multivariate analysis revealed that relative to non-use, cannabis use was associated with higher severity of positive dimension (3-factor: Adjusted Mean Difference, aMD = 0.34, 95% Confidence Interval, CI = [0.03; 0.66]; 5-factor: aMD = 0.38, 95% CI = [0.08; 0.63]), lower severity of negative dimension (3-factor: aMD = -0.49, 95% CI [-0.90; -0.09]; 5-factor: aMD = -0.50, 95% CI = [-0.91; -0.08]), higher severity of excitement dimension (aMD = 0.16, 95% CI = [0.03; 0.28]). No association was found between cannabis use and disorganization (aMD = -0.13, 95% CI = [-0.42; 0.17]) or depression (aMD = -0.14, 95% CI = [-0.34; 0.06]). INTERPRETATION: No causal relationship can be inferred from the current results. The findings could be in favor of both a detrimental and beneficial effect of cannabis on positive and negative symptoms, respectively. Longitudinal designs are needed to understand the role of cannabis is this association. The reported effect sizes are small and CIs are wide, the interpretation of findings should be taken with caution. FUNDING: This research did not receive any specific grant or funding. Primary financial support for authors was provided by Le Vinatier Psychiatric Hospital.

AP HP Department of Psychiatry Louis Mourier Hospital Colombes France

Barcelona Clinic Schizophrenia Unit Neuroscience Institute Hospital Clínic of Barcelona IDIBAPS CIBERSAM University of Barcelona Barcelona Spain

Boston Medical Center Department of Psychiatry 801 Massachusetts Avenue 4th Floor Boston MA 02118 United States of America

Centre for Mental Health County Hospitals Darmstadt Dieburg Groß Umstadt Germany

Centre Hospitalier Le Vinatier Bron France

CHU Lille Fontan Hospital Child and Adolescent Psychiatry Department and CURE Research Platform Lille France

Clienia Littenheid AG Psychiatrische Tagesklinik Frauenfeld 8500 Frauenfeld Switzerland

Department of Experimental Psychology University of Bristol Bristol UK

Department of Neuroscience Imaging Clinical Sciences University of Chieti Pescara Italy

Department of Neuroscience San Luigi Gonzaga University Hospital 10043 Orbassano Italy

Department of Neurosciences and Mental Health Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan Italy

Department of Pathophysiology and Transplantation University of Milan Milan Italy

Department of Psychiatry 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Psychiatry and Mental Health University of Cape Town Cape Town South Africa

Department of Psychiatry and Psychotherapy CCM Charite Universitätsmedizin Berlin Berlin Germany

Department of Psychiatry and Psychotherapy Georg August University Göttingen Germany

Department of Psychiatry and Psychotherapy Ludwig Maximillian University Munich Munich Germany

Department of Psychiatry Boston University School of Medicine 801 Massachusetts Avenue 4th Floor Boston MA 02118 United States of America

Department of Psychiatry Faculty of Medicine and Health Sciences Stellenbosch University Cape Town South Africa

Department of Psychiatry Hotchkiss Brain Institute University of Calgary Calgary Canada

Department of Psychiatry McGill University Montreal Canada

Department of Psychiatry Psychotherapy und Psychosomatic Vivantes Klinikum am Urban und Vivantes Klinikum im Friedrichshain Berlin Germany

Department of Psychiatry QEII Health Sciences Centre Dalhousie University Halifax Nova Scotia Canada

Etiopathogenesis and Treatment of Severe Mental Disorders Institut de Recerca Sant Joan de Déu Spain

General University Hospital Prague Czech Republic

Institute of Clinical Medicine University of Oslo Oslo Norway

Laboratoire de Psychopathologie et Processus de Santé Université Paris Cité F 92100 France

Lille University Inserm U1172 LilNcog Lille Neuroscience and Cognition Plasticity and Subjectivity Team F 59000 Lille France

Medical School Hamburg University of Applied Sciences and Medical University Hamburg Germany

National Institute of Mental Health Klecany Czech Republic

Neuroscience Institute University of Cape Town Cape Town South Africa

NORMENT Centre Division of Mental Health and Addiction Oslo University Hospital and University of Oslo Oslo Norway

Nova Scotia Early Psychosis Program Nova Scotia Health Authority Halifax Nova Scotia Canada

Parc Sanitari Sant Joan de Déu Sant Boi de Llobregat Spain

Pôle Universitaire de Psychiatrie CHU Saint Etienne Saint Etienne France

Psychiatric Genetics Unit Vall d'Hebron Research Institute Barcelona Spain

PSYR CNRL INSERM U1028 CNRS UMR5292 UCBL1 Bron France

Service de biostatistique Hospices Civils de Lyon Lyon France

Service hospitalo universitaire de pharmacotoxicologie Hospices Civils de Lyon Lyon France

Service Universitaire d'Addictologie de Lyon HCL CH Le Vinatier Lyon France

Swiss Research Institute for Public Health and Addiction ISGF University of Zurich Zurich Switzerland

Universitäre Psychiatrische Kliniken Basel Universität Basel Wilhelm Klein Str 27 4002 Basel Switzerland

Université Claude Bernard Lyon 1 Lyon France

Université de Lausanne Institute of Psychology Lausanne Switzerland

Université Paris Cité INSERM UMR1266 Institute of Psychiatry and Neuroscience of Paris France France

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