International forskning

Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies

Marco Solmi 1 2 3 4 5 6 7, Marco De Toffol 8, Jong Yeob Kim 9, Min Je Choi 9, Brendon Stubbs 10 11, Trevor Thompson 12, Joseph Firth 13 14, Alessandro Miola 15, Giovanni Croatto 16, Francesca Baggio 16, Silvia Michelon 17, Luca Ballan 17, Björn Gerdle 18, Francesco Monaco 19 20, Pierluigi Simonato 21, Paolo Scocco 22, Valdo Ricca 23, Giovanni Castellini 23, Michele Fornaro 24, Andrea Murru 25, Eduard Vieta 25, Paolo Fusar-Poli 5 26, Corrado Barbui 27, John P A Ioannidis 28 29 30, Andrè F Carvalho 31, Joaquim Radua 32, Christoph U Correll 7 33 34, Samuele Cortese 6 35 36 37 38, Robin M Murray 39, David Castle 40 41, Jae Il Shin 42 43, Elena Dragioti 18 44

  • 1Department of Psychiatry, University of Ottawa, Ontario, ON, Canada
  • 2On Track: The Champlain First Episode Psychosis Program, Department of Mental Health, The Ottawa Hospital, Ontario, ON, Canada.
  • 3Ottawa Hospital Research Institute, Clinical Epidemiology Program, University of Ottawa, Ottawa, ON, Canada.
  • 4School of Epidemiology and Public Health, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
  • 5Early Psychosis: Interventions and Clinical detection Lab, Institute of Psychiatry, Psychology and Neuroscience, Department of Psychosis Studies, King’s College London, London, UK.
  • 6Centre for Innovation in Mental Health-Developmental Lab, School of Psychology, University of Southampton, and NHS Trust, Southampton, UK.
  • 7Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany.
  • 8Psychiatry Unit, Veris Delli Ponti Scorrano Hospital, Department of Mental Health, ASL Lecce, Lecce, Italy.
  • 9Yonsei University College of Medicine, Seoul, South Korea.
  • 10Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK.
  • 11Physiotherapy Department, South London and Maudsley NHS Foundation Trust, London, UK.
  • 12Centre of Chronic Illness and Ageing, University of Greenwich, London, UK.
  • 13Division of Psychology and Mental Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
  • 14Greater Manchester Mental Health NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
  • 15Neurosciences Department, Padua Neuroscience Center, University of Padua, Italy.
  • 16Mental Health Department, AULSS 3 Serenissima, Mestre, Venice, Italy.
  • 17Department of Mental Health, AULSS 7 Pedemontana Veneto, Italy.
  • 18Pain and Rehabilitation Centre, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
  • 19Department of Mental Health, Asl Salerno, Salerno, Italy.
  • 20European Biomedical Research Institute of Salerno, Salerno, Italy.
  • 21Department of Clinical, Pharmaceutical and Biological Sciences, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, UK.
  • 22Mental Health Department, ULSS 6 Euganea, Padova, Italy.
  • 23Psychiatry Unit, Department of Health Sciences, University of Florence, Florence, Italy.
  • 24Section of Psychiatry, Department of Neuroscience, University School of Medicine Federico II, Naples, Italy.
  • 25Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
  • 26Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.
  • 27WHO Collaborating Centre for Research and Training in Mental Health and Service Evaluation, Department of Neuroscience, Biomedicine and Movement Sciences, Section of Psychiatry, University of Verona, Verona, Italy.
  • 28Meta-Research Innovation Center at Stanford, Stanford University, Stanford, CA, USA.
  • 29Meta-Research Innovation Center Berlin, Berlin Institute of Health, Charité Universitätsmedizin, Berlin, Germany.
  • 30Departments of Medicine, of Epidemiology and Population Health, of Biomedical Data Science, and of Statistics, Stanford University, Stanford, CA, USA.
  • 31IMPACT – The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Deakin University, Geelong, VIC, Australia.
  • 32Institut d’Investigacions Biomediques August Pi i Sunyer, CIBERSAM, Instituto de Salud Carlos III, University of Barcelona, Barcelona, Spain.
  • 33Department of Psychiatry, Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA.
  • 34Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
  • 35Clinical and Experimental Sciences (Central Nervous System and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK.
  • 36Solent NHS Trust, Southampton, UK.
  • 37Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK.
  • 38Hassenfeld Children’s Hospital at NYU Langone, New York University Child Study Center, New York City, New York, NY, USA.
  • 39Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College of London, London, UK.
  • 40Department of Psychiatry, University of Tasmania, Sandy Bay, TAS, Australia.
  • 41Co-Director, Centre for Mental Health Service Innovation, Department of Health, Tasmania, Australia.
  • 42Department of Pediatrics, Yonsei University College of Medicine, Seoul, South Korea.
  • 43Severance Underwood Meta-research Center, Institute of Convergence Science, Yonsei University, Seoul, South Korea.
  • 44Research Laboratory Psychology of Patients, Families and Health Professionals, Department of Nursing, School of Health Sciences, University of Ioannina, Ioannina, Greece.


Objective: To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational studies and randomised controlled trials (RCTs).

Design: Umbrella review.

Data sources: PubMed, PsychInfo, Embase, up to 9 February 2022.

Eligibility criteria for selecting studies: Systematic reviews with meta-analyses of observational studies and RCTs that have reported on the efficacy and safety of cannabis, cannabinoids, or cannabis based medicines were included. Credibility was graded according to convincing, highly suggestive, suggestive, weak, or not significant (observational evidence), and by GRADE (Grading of Recommendations, Assessment, Development and Evaluations) (RCTs). Quality was assessed with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). Sensitivity analyses were conducted.

Results: 101 meta-analyses were included (observational=50, RCTs=51) (AMSTAR 2 high 33, moderate 31, low 32, or critically low 5). From RCTs supported by high to moderate certainty, cannabis based medicines increased adverse events related to the central nervous system (equivalent odds ratio 2.84 (95% confidence interval 2.16 to 3.73)), psychological effects (3.07 (1.79 to 5.26)), and vision (3.00 (1.79 to 5.03)) in people with mixed conditions (GRADE=high), improved nausea/vomit, pain, spasticity, but increased psychiatric, gastrointestinal adverse events, and somnolence among others (GRADE=moderate). Cannabidiol improved 50% reduction of seizures (0.59 (0.38 to 0.92)) and seizure events (0.59 (0.36 to 0.96)) (GRADE=high), but increased pneumonia, gastrointestinal adverse events, and somnolence (GRADE=moderate). For chronic pain, cannabis based medicines or cannabinoids reduced pain by 30% (0.59 (0.37 to 0.93), GRADE=high), across different conditions (n=7), but increased psychological distress. For epilepsy, cannabidiol increased risk of diarrhoea (2.25 (1.33 to 3.81)), had no effect on sleep disruption (GRADE=high), reduced seizures across different populations and measures (n=7), improved global impression (n=2), quality of life, and increased risk of somnolence (GRADE=moderate). In the general population, cannabis worsened positive psychotic symptoms (5.21 (3.36 to 8.01)) and total psychiatric symptoms (7.49 (5.31 to 10.42)) (GRADE=high), negative psychotic symptoms, and cognition (n=11) (GRADE=moderate). In healthy people, cannabinoids improved pain threshold (0.74 (0.59 to 0.91)), unpleasantness (0.60 (0.41 to 0.88)) (GRADE=high). For inflammatory bowel disease, cannabinoids improved quality of life (0.34 (0.22 to 0.53) (GRADE=high). For multiple sclerosis, cannabinoids improved spasticity, pain, but increased risk of dizziness, dry mouth, nausea, somnolence (GRADE=moderate). For cancer, cannabinoids improved sleep disruption, but had gastrointestinal adverse events (n=2) (GRADE=moderate). Cannabis based medicines, cannabis, and cannabinoids resulted in poor tolerability across various conditions (GRADE=moderate). Evidence was convincing from observational studies (main and sensitivity analyses) in pregnant women, small for gestational age (1.61 (1.41 to 1.83)), low birth weight (1.43 (1.27 to 1.62)); in drivers, car crash (1.27 (1.21 to 1.34)); and in the general population, psychosis (1.71 (1.47 to 2.00)). Harmful effects were noted for additional neonatal outcomes, outcomes related to car crash, outcomes in the general population including psychotic symptoms, suicide attempt, depression, and mania, and impaired cognition in healthy cannabis users (all suggestive to highly suggestive).

Conclusions: Convincing or converging evidence supports avoidance of cannabis during adolescence and early adulthood, in people prone to or with mental health disorders, in pregnancy and before and while driving. Cannabidiol is effective in people with epilepsy. Cannabis based medicines are effective in people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative medicine but not without adverse events.