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

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 F...

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Autores principales: Solmi, Marco, De Toffol, Marco, Kim, Jong Yeob, Choi, Min Je, Stubbs, Brendon, Thompson, Trevor, Firth, Joseph, Miola, Alessandro, Croatto, Giovanni, Baggio, Francesca, Michelon, Silvia, Ballan, Luca, Gerdle, Björn, Monaco, Francesco, Simonato, Pierluigi, Scocco, Paolo, Ricca, Valdo, Castellini, Giovanni, Fornaro, Michele, Murru, Andrea, Vieta, Eduard, Fusar-Poli, Paolo, Barbui, Corrado, Ioannidis, John P A, Carvalho, Andrè F, Radua, Joaquim, Correll, Christoph U, Cortese, Samuele, Murray, Robin M, Castle, David, Shin, Jae Il, Dragioti, Elena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group Ltd. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10466434/
https://www.ncbi.nlm.nih.gov/pubmed/37648266
http://dx.doi.org/10.1136/bmj-2022-072348
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author Solmi, Marco
De Toffol, Marco
Kim, Jong Yeob
Choi, Min Je
Stubbs, Brendon
Thompson, Trevor
Firth, Joseph
Miola, Alessandro
Croatto, Giovanni
Baggio, Francesca
Michelon, Silvia
Ballan, Luca
Gerdle, Björn
Monaco, Francesco
Simonato, Pierluigi
Scocco, Paolo
Ricca, Valdo
Castellini, Giovanni
Fornaro, Michele
Murru, Andrea
Vieta, Eduard
Fusar-Poli, Paolo
Barbui, Corrado
Ioannidis, John P A
Carvalho, Andrè F
Radua, Joaquim
Correll, Christoph U
Cortese, Samuele
Murray, Robin M
Castle, David
Shin, Jae Il
Dragioti, Elena
author_facet Solmi, Marco
De Toffol, Marco
Kim, Jong Yeob
Choi, Min Je
Stubbs, Brendon
Thompson, Trevor
Firth, Joseph
Miola, Alessandro
Croatto, Giovanni
Baggio, Francesca
Michelon, Silvia
Ballan, Luca
Gerdle, Björn
Monaco, Francesco
Simonato, Pierluigi
Scocco, Paolo
Ricca, Valdo
Castellini, Giovanni
Fornaro, Michele
Murru, Andrea
Vieta, Eduard
Fusar-Poli, Paolo
Barbui, Corrado
Ioannidis, John P A
Carvalho, Andrè F
Radua, Joaquim
Correll, Christoph U
Cortese, Samuele
Murray, Robin M
Castle, David
Shin, Jae Il
Dragioti, Elena
author_sort Solmi, Marco
collection PubMed
description 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. STUDY REGISTRATION: PROSPERO CRD42018093045. FUNDING: None.
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spelling pubmed-104664342023-08-31 Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies Solmi, Marco De Toffol, Marco Kim, Jong Yeob Choi, Min Je Stubbs, Brendon Thompson, Trevor Firth, Joseph Miola, Alessandro Croatto, Giovanni Baggio, Francesca Michelon, Silvia Ballan, Luca Gerdle, Björn Monaco, Francesco Simonato, Pierluigi Scocco, Paolo Ricca, Valdo Castellini, Giovanni Fornaro, Michele Murru, Andrea Vieta, Eduard Fusar-Poli, Paolo Barbui, Corrado Ioannidis, John P A Carvalho, Andrè F Radua, Joaquim Correll, Christoph U Cortese, Samuele Murray, Robin M Castle, David Shin, Jae Il Dragioti, Elena BMJ Research 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. STUDY REGISTRATION: PROSPERO CRD42018093045. FUNDING: None. BMJ Publishing Group Ltd. 2023-08-30 /pmc/articles/PMC10466434/ /pubmed/37648266 http://dx.doi.org/10.1136/bmj-2022-072348 Text en © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Research
Solmi, Marco
De Toffol, Marco
Kim, Jong Yeob
Choi, Min Je
Stubbs, Brendon
Thompson, Trevor
Firth, Joseph
Miola, Alessandro
Croatto, Giovanni
Baggio, Francesca
Michelon, Silvia
Ballan, Luca
Gerdle, Björn
Monaco, Francesco
Simonato, Pierluigi
Scocco, Paolo
Ricca, Valdo
Castellini, Giovanni
Fornaro, Michele
Murru, Andrea
Vieta, Eduard
Fusar-Poli, Paolo
Barbui, Corrado
Ioannidis, John P A
Carvalho, Andrè F
Radua, Joaquim
Correll, Christoph U
Cortese, Samuele
Murray, Robin M
Castle, David
Shin, Jae Il
Dragioti, Elena
Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies
title Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies
title_full Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies
title_fullStr Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies
title_full_unstemmed Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies
title_short Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies
title_sort balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10466434/
https://www.ncbi.nlm.nih.gov/pubmed/37648266
http://dx.doi.org/10.1136/bmj-2022-072348
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