Burden of disease due to amphetamines, cannabis, cocaine, and opioid use disorders in South America, 1990–2019: a systematic analysis of the Global Burden of Disease Study 2019

Background South America’s substance use profile, poverty, income inequality, and cocaine-supplier role make it a unique place for substance use research. This study investigated the burden of disease attributable to amphetamine use disorder, cannabis use disorder (CAD), cocaine use disorder, and op...

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Autores:
Buendía Rodríguez, Jefferson Antonio
Castaldelli Maia, João M.
Wang, Yuan Pang
Brunoni, Andre R
Faro, Andre
Tipo de recurso:
Article of investigation
Fecha de publicación:
2023
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/47838
Acceso en línea:
https://hdl.handle.net/10495/47838
Palabra clave:
Amphetamines
Anfetaminas
Global Burden of Disease
Carga Global de Enfermedades
Global Health
Salud Global
Quality-Adjusted Life Years
Años de Vida Ajustados por Calidad de Vida
Substance-Related Disorders
Trastornos Relacionados con Sustancias
Cannabis
América del Sur
South America
https://id.nlm.nih.gov/mesh/D000662
https://id.nlm.nih.gov/mesh/D000071219
https://id.nlm.nih.gov/mesh/D014943
https://id.nlm.nih.gov/mesh/D019057
https://id.nlm.nih.gov/mesh/D019966
https://id.nlm.nih.gov/mesh/D002188
https://id.nlm.nih.gov/mesh/D013020
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
Rights
openAccess
License
http://creativecommons.org/licenses/by-nc-nd/4.0/
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oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/47838
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.eng.fl_str_mv Burden of disease due to amphetamines, cannabis, cocaine, and opioid use disorders in South America, 1990–2019: a systematic analysis of the Global Burden of Disease Study 2019
title Burden of disease due to amphetamines, cannabis, cocaine, and opioid use disorders in South America, 1990–2019: a systematic analysis of the Global Burden of Disease Study 2019
spellingShingle Burden of disease due to amphetamines, cannabis, cocaine, and opioid use disorders in South America, 1990–2019: a systematic analysis of the Global Burden of Disease Study 2019
Amphetamines
Anfetaminas
Global Burden of Disease
Carga Global de Enfermedades
Global Health
Salud Global
Quality-Adjusted Life Years
Años de Vida Ajustados por Calidad de Vida
Substance-Related Disorders
Trastornos Relacionados con Sustancias
Cannabis
América del Sur
South America
https://id.nlm.nih.gov/mesh/D000662
https://id.nlm.nih.gov/mesh/D000071219
https://id.nlm.nih.gov/mesh/D014943
https://id.nlm.nih.gov/mesh/D019057
https://id.nlm.nih.gov/mesh/D019966
https://id.nlm.nih.gov/mesh/D002188
https://id.nlm.nih.gov/mesh/D013020
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
title_short Burden of disease due to amphetamines, cannabis, cocaine, and opioid use disorders in South America, 1990–2019: a systematic analysis of the Global Burden of Disease Study 2019
title_full Burden of disease due to amphetamines, cannabis, cocaine, and opioid use disorders in South America, 1990–2019: a systematic analysis of the Global Burden of Disease Study 2019
title_fullStr Burden of disease due to amphetamines, cannabis, cocaine, and opioid use disorders in South America, 1990–2019: a systematic analysis of the Global Burden of Disease Study 2019
title_full_unstemmed Burden of disease due to amphetamines, cannabis, cocaine, and opioid use disorders in South America, 1990–2019: a systematic analysis of the Global Burden of Disease Study 2019
title_sort Burden of disease due to amphetamines, cannabis, cocaine, and opioid use disorders in South America, 1990–2019: a systematic analysis of the Global Burden of Disease Study 2019
dc.creator.fl_str_mv Buendía Rodríguez, Jefferson Antonio
Castaldelli Maia, João M.
Wang, Yuan Pang
Brunoni, Andre R
Faro, Andre
dc.contributor.author.none.fl_str_mv Buendía Rodríguez, Jefferson Antonio
Castaldelli Maia, João M.
Wang, Yuan Pang
Brunoni, Andre R
Faro, Andre
dc.contributor.researchgroup.none.fl_str_mv Grupo de Investigación en Farmacología y Toxicología
dc.subject.decs.none.fl_str_mv Amphetamines
Anfetaminas
Global Burden of Disease
Carga Global de Enfermedades
Global Health
Salud Global
Quality-Adjusted Life Years
Años de Vida Ajustados por Calidad de Vida
Substance-Related Disorders
Trastornos Relacionados con Sustancias
Cannabis
América del Sur
South America
topic Amphetamines
Anfetaminas
Global Burden of Disease
Carga Global de Enfermedades
Global Health
Salud Global
Quality-Adjusted Life Years
Años de Vida Ajustados por Calidad de Vida
Substance-Related Disorders
Trastornos Relacionados con Sustancias
Cannabis
América del Sur
South America
https://id.nlm.nih.gov/mesh/D000662
https://id.nlm.nih.gov/mesh/D000071219
https://id.nlm.nih.gov/mesh/D014943
https://id.nlm.nih.gov/mesh/D019057
https://id.nlm.nih.gov/mesh/D019966
https://id.nlm.nih.gov/mesh/D002188
https://id.nlm.nih.gov/mesh/D013020
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
dc.subject.meshuri.none.fl_str_mv https://id.nlm.nih.gov/mesh/D000662
https://id.nlm.nih.gov/mesh/D000071219
https://id.nlm.nih.gov/mesh/D014943
https://id.nlm.nih.gov/mesh/D019057
https://id.nlm.nih.gov/mesh/D019966
https://id.nlm.nih.gov/mesh/D002188
https://id.nlm.nih.gov/mesh/D013020
dc.subject.ods.none.fl_str_mv ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
description Background South America’s substance use profile, poverty, income inequality, and cocaine-supplier role make it a unique place for substance use research. This study investigated the burden of disease attributable to amphetamine use disorder, cannabis use disorder (CAD), cocaine use disorder, and opioid use disorder (OUD) in South America from 1990 to 2019, on the basis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods GBD 2019 estimated the incidence, prevalence, mortality, years of life lost (YLL), years of life lived with disability (YLD), and disability-adjusted life-years (DALYs) due to substance use disorders in each of the 12 South American countries (Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Guyana, Paraguay, Peru, Suriname, Uruguay, and Venezuela). Data were modelled using standardised tools (ie, the Cause of Death Ensemble model, spatio-temporal Gaussian process regression, and disease modelling meta-regression) to generate estimates of each quantity of interest by sex, location, and year. The analysis included comparisons by sex and country, and against regional and global estimates. Findings In 2019, the highest amphetamine use disorder burden per 100000 population in South America was in Peru (66 DALYs). CAD DALY rates per 100000 in South America were stable between 1990 and 2019, except in Chile and Colombia, which had the highest rates in 2019 (19 DALYs for Chile and 18 DALYs for Colombia). OUD DALYs per 100000 increased during the period in Brazil and Peru, which in 2019 had the highest rates in South America (82 DALYs for Brazil and 70 DALYs for Peru). In 2019, Brazil had the highest cocaine use disorder DALYs per 100000 (45 DALYs), nearly double its rate in 1990. DALY rates were higher in males than females for each substance use disorder, except in Paraguay. The overall burden of substance use disorders was higher in males than in females, mainly because of cocaine use disorder and CAD, whereas for amphetamine use disorder, the difference between sexes was minimal, and for OUD there was no difference. For males and females, the highest rate of substance use disorders DALYs per 100000 was for OUD except in Argentina (in males, 58 DALYs for cocaine use disorder vs 52 DALYs for OUD) and in Paraguay (in females, 77 for amphetamine use disorder vs 50 for OUD). CAD DALY rates were generally the lowest among the substance use disorders for males and females. Amphetamine use disorder YLD rates were reasonably stable throughout the period and were highest in Peru, Paraguay, and Uruguay (>40 YLD per 100000). For CAD, YLD rates were stable in all countries except Chile and Colombia. Cocaine use disorder YLD rates per 100000 for the top four countries (Argentina, Uruguay, Chile, and Brazil) increased from 1990 to 2010 (eg, from 19 to 33 in Brazil), but decreased between 2010 and 2019 (eg, from 36 to 31 in Chile). For OUD, YLD rates showed a slight increase in most countries apart from Brazil, which increased from 52 in 1990 to 80 in 2019 and was top among the countries. Amphetamine use disorder YLL rates per 100000 were highest in Suriname and Peru during the period, although in Suriname it increased from 2·7 in 2010 to 3·2 in 2019, whereas in Peru it decreased from 2·1 to 1·7. The highest YLL rate for cocaine use disorder was in Brazil, which increased from 3·7 in 1990 to 18·1 in 2019. Between 2000 and 2019, Chile and Uruguay showed the highest OUD YLL rates (11·6 for Chile and 10·9 for Uruguay). A high incidence of CAD was found in Chile, Colombia, Guyana, and Suriname. There were high incidences of amphetamine use disorder in Paraguay, cocaine use disorder in Argentina, and OUD in Ecuador. A decrease in annual prevalence for substance use disorders during the period was observed in Venezuela (amphetamine use disorder, CAD, and OUD), Brazil (CAD and amphetamine use disorder), Colombia (amphetamine use disorder and cocaine use disorder), Peru (amphetamine use disorder and cocaine use disorder), Chile and Suriname (amphetamine use disorder), Uruguay (CAD), and Bolivia (OUD). Overall, the cocaine use disorder burden stabilised then decreased. OUD was less prevalent than other substance use disorders but its burden was the highest. Interpretation The decrease in the burden of cocaine use disorder probably reflects the success of national standardised treatment programmes. Programmes for amphetamine use disorder, CAD, and OUD management should be improved. We did not find an increase in CAD burden in Uruguay, the country with the highest degree of cannabis decriminalisation in the region. Countries in South America should improve monitoring of substance use disorders, including regular surveys to provide more accurate data on which to base policy decisions.
publishDate 2023
dc.date.issued.none.fl_str_mv 2023
dc.date.accessioned.none.fl_str_mv 2025-10-19T14:22:50Z
dc.type.none.fl_str_mv Artículo de investigación
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dc.identifier.citation.none.fl_str_mv Castaldelli-Maia, J. M., Wang, Y. P., Brunoni, A. R., Faro, A., Guimarães, R. A., Lucchetti, G., Martorell, M., Moreira, R. S., Pacheco-Barrios, K., Rodriguez, J. A. B., Roever, L., Silva, D. A. S., Tovani-Palone, M. R., Valdez, P. R., Zimmermann, I. R., Culbreth, G. T., Hay, S. I., Murray, C. J. L., & Bensenor, I. M. (2023). Burden of disease due to amphetamines, cannabis, cocaine, and opioid use disorders in South America, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019. The lancet. Psychiatry, 10(2), 85–97. https://doi.org/10.1016/S2215-0366(22)00339-X
dc.identifier.issn.none.fl_str_mv 2215-0366
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dc.identifier.eissn.none.fl_str_mv 2215-0374
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identifier_str_mv Castaldelli-Maia, J. M., Wang, Y. P., Brunoni, A. R., Faro, A., Guimarães, R. A., Lucchetti, G., Martorell, M., Moreira, R. S., Pacheco-Barrios, K., Rodriguez, J. A. B., Roever, L., Silva, D. A. S., Tovani-Palone, M. R., Valdez, P. R., Zimmermann, I. R., Culbreth, G. T., Hay, S. I., Murray, C. J. L., & Bensenor, I. M. (2023). Burden of disease due to amphetamines, cannabis, cocaine, and opioid use disorders in South America, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019. The lancet. Psychiatry, 10(2), 85–97. https://doi.org/10.1016/S2215-0366(22)00339-X
2215-0366
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dc.relation.citationendpage.none.fl_str_mv 97
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dc.relation.citationstartpage.none.fl_str_mv 85
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dc.relation.ispartofjournal.none.fl_str_mv The Lancet Psychatry
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dc.format.extent.none.fl_str_mv 13 páginas
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dc.coverage.temporal.none.fl_str_mv 1990-2019
América del Sur
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dc.publisher.none.fl_str_mv Elsevier
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publisher.none.fl_str_mv Elsevier
institution Universidad de Antioquia
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spelling Buendía Rodríguez, Jefferson AntonioCastaldelli Maia, João M.Wang, Yuan PangBrunoni, Andre RFaro, AndreGrupo de Investigación en Farmacología y Toxicología1990-2019América del SurLat: 03 33 00 S degrees minutes Lat: -3.5500 decimal degrees Long: 056 41 00 W degrees minutes Long: -56.6830 decimal degreeshttp://vocab.getty.edu/page/tgn/10000022025-10-19T14:22:50Z2023Castaldelli-Maia, J. M., Wang, Y. P., Brunoni, A. R., Faro, A., Guimarães, R. A., Lucchetti, G., Martorell, M., Moreira, R. S., Pacheco-Barrios, K., Rodriguez, J. A. B., Roever, L., Silva, D. A. S., Tovani-Palone, M. R., Valdez, P. R., Zimmermann, I. R., Culbreth, G. T., Hay, S. I., Murray, C. J. L., & Bensenor, I. M. (2023). Burden of disease due to amphetamines, cannabis, cocaine, and opioid use disorders in South America, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019. The lancet. Psychiatry, 10(2), 85–97. https://doi.org/10.1016/S2215-0366(22)00339-X2215-0366https://hdl.handle.net/10495/4783810.1016/S2215-0366(22)00339-X2215-037436697127Background South America’s substance use profile, poverty, income inequality, and cocaine-supplier role make it a unique place for substance use research. This study investigated the burden of disease attributable to amphetamine use disorder, cannabis use disorder (CAD), cocaine use disorder, and opioid use disorder (OUD) in South America from 1990 to 2019, on the basis of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods GBD 2019 estimated the incidence, prevalence, mortality, years of life lost (YLL), years of life lived with disability (YLD), and disability-adjusted life-years (DALYs) due to substance use disorders in each of the 12 South American countries (Argentina, Bolivia, Brazil, Chile, Colombia, Ecuador, Guyana, Paraguay, Peru, Suriname, Uruguay, and Venezuela). Data were modelled using standardised tools (ie, the Cause of Death Ensemble model, spatio-temporal Gaussian process regression, and disease modelling meta-regression) to generate estimates of each quantity of interest by sex, location, and year. The analysis included comparisons by sex and country, and against regional and global estimates. Findings In 2019, the highest amphetamine use disorder burden per 100000 population in South America was in Peru (66 DALYs). CAD DALY rates per 100000 in South America were stable between 1990 and 2019, except in Chile and Colombia, which had the highest rates in 2019 (19 DALYs for Chile and 18 DALYs for Colombia). OUD DALYs per 100000 increased during the period in Brazil and Peru, which in 2019 had the highest rates in South America (82 DALYs for Brazil and 70 DALYs for Peru). In 2019, Brazil had the highest cocaine use disorder DALYs per 100000 (45 DALYs), nearly double its rate in 1990. DALY rates were higher in males than females for each substance use disorder, except in Paraguay. The overall burden of substance use disorders was higher in males than in females, mainly because of cocaine use disorder and CAD, whereas for amphetamine use disorder, the difference between sexes was minimal, and for OUD there was no difference. For males and females, the highest rate of substance use disorders DALYs per 100000 was for OUD except in Argentina (in males, 58 DALYs for cocaine use disorder vs 52 DALYs for OUD) and in Paraguay (in females, 77 for amphetamine use disorder vs 50 for OUD). CAD DALY rates were generally the lowest among the substance use disorders for males and females. Amphetamine use disorder YLD rates were reasonably stable throughout the period and were highest in Peru, Paraguay, and Uruguay (>40 YLD per 100000). For CAD, YLD rates were stable in all countries except Chile and Colombia. Cocaine use disorder YLD rates per 100000 for the top four countries (Argentina, Uruguay, Chile, and Brazil) increased from 1990 to 2010 (eg, from 19 to 33 in Brazil), but decreased between 2010 and 2019 (eg, from 36 to 31 in Chile). For OUD, YLD rates showed a slight increase in most countries apart from Brazil, which increased from 52 in 1990 to 80 in 2019 and was top among the countries. Amphetamine use disorder YLL rates per 100000 were highest in Suriname and Peru during the period, although in Suriname it increased from 2·7 in 2010 to 3·2 in 2019, whereas in Peru it decreased from 2·1 to 1·7. The highest YLL rate for cocaine use disorder was in Brazil, which increased from 3·7 in 1990 to 18·1 in 2019. Between 2000 and 2019, Chile and Uruguay showed the highest OUD YLL rates (11·6 for Chile and 10·9 for Uruguay). A high incidence of CAD was found in Chile, Colombia, Guyana, and Suriname. There were high incidences of amphetamine use disorder in Paraguay, cocaine use disorder in Argentina, and OUD in Ecuador. A decrease in annual prevalence for substance use disorders during the period was observed in Venezuela (amphetamine use disorder, CAD, and OUD), Brazil (CAD and amphetamine use disorder), Colombia (amphetamine use disorder and cocaine use disorder), Peru (amphetamine use disorder and cocaine use disorder), Chile and Suriname (amphetamine use disorder), Uruguay (CAD), and Bolivia (OUD). Overall, the cocaine use disorder burden stabilised then decreased. OUD was less prevalent than other substance use disorders but its burden was the highest. Interpretation The decrease in the burden of cocaine use disorder probably reflects the success of national standardised treatment programmes. Programmes for amphetamine use disorder, CAD, and OUD management should be improved. We did not find an increase in CAD burden in Uruguay, the country with the highest degree of cannabis decriminalisation in the region. Countries in South America should improve monitoring of substance use disorders, including regular surveys to provide more accurate data on which to base policy decisions.COL003990213 páginasapplication/pdfengElsevierOxford, Inglaterrahttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://purl.org/coar/access_right/c_abf2Burden of disease due to amphetamines, cannabis, cocaine, and opioid use disorders in South America, 1990–2019: a systematic analysis of the Global Burden of Disease Study 2019Artículo de investigaciónhttp://purl.org/coar/resource_type/c_2df8fbb1http://purl.org/redcol/resource_type/ARTTexthttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionAmphetaminesAnfetaminasGlobal Burden of DiseaseCarga Global de EnfermedadesGlobal HealthSalud GlobalQuality-Adjusted Life YearsAños de Vida Ajustados por Calidad de VidaSubstance-Related DisordersTrastornos Relacionados con SustanciasCannabisAmérica del SurSouth Americahttps://id.nlm.nih.gov/mesh/D000662https://id.nlm.nih.gov/mesh/D000071219https://id.nlm.nih.gov/mesh/D014943https://id.nlm.nih.gov/mesh/D019057https://id.nlm.nih.gov/mesh/D019966https://id.nlm.nih.gov/mesh/D002188https://id.nlm.nih.gov/mesh/D013020ODS 3: Salud y bienestar. 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