Avaliação do perfil toxicológico in silico e in vivo de extratos da planta Cannabis sativa L. contendo os fitocanabinoides canabidiol e Δ9-tetraidrocanabinol

Detalhes bibliográficos
Ano de defesa: 2025
Autor(a) principal: Aquino, Débora Nascimento de
Orientador(a): Não Informado pela instituição
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal da Paraíba
Brasil
Farmacologia
Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos
UFPB
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: https://repositorio.ufpb.br/jspui/handle/123456789/37424
Resumo: Cannabis sativa L., used for millennia for medicinal and industrial purposes, has a complex chemical composition, with particular emphasis on phytocannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC). Despite advances in pharmacological research, gaps remain regarding the toxicity of full-spectrum extracts, which are essential to support their safe therapeutic use. This study aimed to evaluate the in silico toxicity of isolated Δ9-THC and CBD, as well as the acute toxicological profile of a full-spectrum extract enriched with Δ9-THC and CBD, identifying potential toxicity targets and contributing to a better understanding of their safety. For the in silico assessment, three computational tools were employed: ADMETsar, PASS online, and ProTox. The in silico results indicated acute oral toxicity classes III and IV for the chemical structures of Δ9-tetrahydrocannabinol and cannabidiol, respectively, according to the ADMETsar and ProTox analyses. Additionally, several toxicity endpoints were predicted, including respiratory toxicity, immunotoxicity, and ecotoxicity, among others. An acute oral toxicity test was conducted in an animal model following the OECD Guideline 423 (2001), using a single administration of 2000 mg/kg with a 14-day observation period. Pharmacological screening was performed, and parameters were monitored throughout the 14 days. After euthanasia, blood samples were collected for hematological and biochemical analyses. Macroscopic necropsy and histopathological examinations were also carried out. Regarding acute toxicity, no alterations were observed in hematological and histopathological parameters. The results demonstrate a favorable safety profile for the full-spectrum Cannabis sativa extract enriched with Δ9-THC and CBD, supporting its potential for controlled therapeutic applications. This research provides a scientific basis for the regulation of cannabis-based products in Brazil, contributing to clinical and regulatory decisionmaking by ANVISA.
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spelling Avaliação do perfil toxicológico in silico e in vivo de extratos da planta Cannabis sativa L. contendo os fitocanabinoides canabidiol e Δ9-tetraidrocanabinolCannabis sativa L.Canabidiol (CBD)Δ9-tetraidrocanabinol (Δ9- THC)ToxicologiaTeste in silicoOECD 423Δ9-tetrahydrocannabinol (Δ9- THC)ToxicologyIn silico testCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIACannabis sativa L., used for millennia for medicinal and industrial purposes, has a complex chemical composition, with particular emphasis on phytocannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC). Despite advances in pharmacological research, gaps remain regarding the toxicity of full-spectrum extracts, which are essential to support their safe therapeutic use. This study aimed to evaluate the in silico toxicity of isolated Δ9-THC and CBD, as well as the acute toxicological profile of a full-spectrum extract enriched with Δ9-THC and CBD, identifying potential toxicity targets and contributing to a better understanding of their safety. For the in silico assessment, three computational tools were employed: ADMETsar, PASS online, and ProTox. The in silico results indicated acute oral toxicity classes III and IV for the chemical structures of Δ9-tetrahydrocannabinol and cannabidiol, respectively, according to the ADMETsar and ProTox analyses. Additionally, several toxicity endpoints were predicted, including respiratory toxicity, immunotoxicity, and ecotoxicity, among others. An acute oral toxicity test was conducted in an animal model following the OECD Guideline 423 (2001), using a single administration of 2000 mg/kg with a 14-day observation period. Pharmacological screening was performed, and parameters were monitored throughout the 14 days. After euthanasia, blood samples were collected for hematological and biochemical analyses. Macroscopic necropsy and histopathological examinations were also carried out. Regarding acute toxicity, no alterations were observed in hematological and histopathological parameters. The results demonstrate a favorable safety profile for the full-spectrum Cannabis sativa extract enriched with Δ9-THC and CBD, supporting its potential for controlled therapeutic applications. This research provides a scientific basis for the regulation of cannabis-based products in Brazil, contributing to clinical and regulatory decisionmaking by ANVISA.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESA Cannabis sativa L., utilizada há milênios para fins medicinais e industriais, possui uma composição química complexa, com destaque para os fitocanabinoides, como o canabidiol (CBD) e o Δ9-tetraidrocanabinol (Δ9-THC). Apesar do avanço nas pesquisas farmacológicas, lacunas persistem quanto à toxicidade de extratos integrais (full spectrum), essenciais para embasar seu uso terapêutico seguro. Este estudo teve como objetivo avaliar a toxicidade in silico do Δ9-THC e CBD isolados, e o perfil toxicológico agudo do extrato integral enriquecido com Δ9-THC e CBD, identificando possíveis alvos de toxicidade e contribuindo para a compreensão de sua segurança. No teste in silico, três ferramentas foram utilizadas: ADMETsar, Pass online e ProTox. Os resultados in silico apresentaram toxicidade oral aguda classe III e IV para a estrutura química do delta-9-tetraidrocanabinol e canabidiol nos testes ADMETsar e ProTox respectivamente. Além de demonstrar pontos finais de toxicidade para diversos alvos, entre eles, toxicidade respiratória, imunotoxicidade, ecotoxicidade, entre outros. Foi realizado um teste de toxicidade oral aguda, seguindo o protocolo OECD 423 (2001), em modelo animal, com administração única de 2000 mg/kg e observação por 14 dias. Foi realizada a triagem farmacológica e parâmetros durante os 14 dias foram observados. Após a eutanásia, amostras de sangue foram coletadas para análises laboratoriais de parâmetros hematológicos e bioquímicos. Uma necropsia macroscópica foi realizada e análise histopatológica foi conduzida. Em relação à toxicidade aguda, nenhuma alteração nos parâmetros hematológicos e histopatológicos foram observadas. Os resultados demonstram um perfil de segurança favorável para o extrato integral de Cannabis sativa enriquecido com Δ9-THC e CBD, alinhando-se a aplicações terapêuticas controladas. Esta pesquisa fornece bases científicas para a regulamentação de produtos à base de Cannabis no Brasil, subsidiando decisões clínicas e normativas pela ANVISA.Universidade Federal da ParaíbaBrasilFarmacologiaPrograma de Pós-Graduação em Produtos Naturais e Sintéticos BioativosUFPBDiniz, Margareth de Fátima Formiga Melohttp://lattes.cnpq.br/4173269414899195Donato, Micheline Freirehttp://lattes.cnpq.br/8164809353750371Belém, Lindomar de Fariashttp://lattes.cnpq.br/6227853111328214Pessoa, Hilzeth de Luna Freirehttp://lattes.cnpq.br/8141500406366011Farias, Davi Felipehttp://lattes.cnpq.br/7568220396626488Castro, Ricardo Dias dehttp://lattes.cnpq.br/0031529469046003Aquino, Débora Nascimento de2026-01-26T10:25:05Z2025-12-022026-01-26T10:25:05Z2025-08-26info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesishttps://repositorio.ufpb.br/jspui/handle/123456789/37424porAttribution-NoDerivs 3.0 Brazilhttp://creativecommons.org/licenses/by-nd/3.0/br/info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2026-01-27T06:05:51Zoai:repositorio.ufpb.br:123456789/37424Repositório InstitucionalPUBhttps://repositorio.ufpb.br/oai/requestdiretoria@ufpb.br||bdtd@biblioteca.ufpb.bropendoar:25462026-01-27T06:05:51Repositório Institucional da UFPB - Universidade Federal da Paraíba (UFPB)false
dc.title.none.fl_str_mv Avaliação do perfil toxicológico in silico e in vivo de extratos da planta Cannabis sativa L. contendo os fitocanabinoides canabidiol e Δ9-tetraidrocanabinol
title Avaliação do perfil toxicológico in silico e in vivo de extratos da planta Cannabis sativa L. contendo os fitocanabinoides canabidiol e Δ9-tetraidrocanabinol
spellingShingle Avaliação do perfil toxicológico in silico e in vivo de extratos da planta Cannabis sativa L. contendo os fitocanabinoides canabidiol e Δ9-tetraidrocanabinol
Aquino, Débora Nascimento de
Cannabis sativa L.
Canabidiol (CBD)
Δ9-tetraidrocanabinol (Δ9- THC)
Toxicologia
Teste in silico
OECD 423
Δ9-tetrahydrocannabinol (Δ9- THC)
Toxicology
In silico test
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
title_short Avaliação do perfil toxicológico in silico e in vivo de extratos da planta Cannabis sativa L. contendo os fitocanabinoides canabidiol e Δ9-tetraidrocanabinol
title_full Avaliação do perfil toxicológico in silico e in vivo de extratos da planta Cannabis sativa L. contendo os fitocanabinoides canabidiol e Δ9-tetraidrocanabinol
title_fullStr Avaliação do perfil toxicológico in silico e in vivo de extratos da planta Cannabis sativa L. contendo os fitocanabinoides canabidiol e Δ9-tetraidrocanabinol
title_full_unstemmed Avaliação do perfil toxicológico in silico e in vivo de extratos da planta Cannabis sativa L. contendo os fitocanabinoides canabidiol e Δ9-tetraidrocanabinol
title_sort Avaliação do perfil toxicológico in silico e in vivo de extratos da planta Cannabis sativa L. contendo os fitocanabinoides canabidiol e Δ9-tetraidrocanabinol
author Aquino, Débora Nascimento de
author_facet Aquino, Débora Nascimento de
author_role author
dc.contributor.none.fl_str_mv Diniz, Margareth de Fátima Formiga Melo
http://lattes.cnpq.br/4173269414899195
Donato, Micheline Freire
http://lattes.cnpq.br/8164809353750371
Belém, Lindomar de Farias
http://lattes.cnpq.br/6227853111328214
Pessoa, Hilzeth de Luna Freire
http://lattes.cnpq.br/8141500406366011
Farias, Davi Felipe
http://lattes.cnpq.br/7568220396626488
Castro, Ricardo Dias de
http://lattes.cnpq.br/0031529469046003
dc.contributor.author.fl_str_mv Aquino, Débora Nascimento de
dc.subject.por.fl_str_mv Cannabis sativa L.
Canabidiol (CBD)
Δ9-tetraidrocanabinol (Δ9- THC)
Toxicologia
Teste in silico
OECD 423
Δ9-tetrahydrocannabinol (Δ9- THC)
Toxicology
In silico test
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
topic Cannabis sativa L.
Canabidiol (CBD)
Δ9-tetraidrocanabinol (Δ9- THC)
Toxicologia
Teste in silico
OECD 423
Δ9-tetrahydrocannabinol (Δ9- THC)
Toxicology
In silico test
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
description Cannabis sativa L., used for millennia for medicinal and industrial purposes, has a complex chemical composition, with particular emphasis on phytocannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC). Despite advances in pharmacological research, gaps remain regarding the toxicity of full-spectrum extracts, which are essential to support their safe therapeutic use. This study aimed to evaluate the in silico toxicity of isolated Δ9-THC and CBD, as well as the acute toxicological profile of a full-spectrum extract enriched with Δ9-THC and CBD, identifying potential toxicity targets and contributing to a better understanding of their safety. For the in silico assessment, three computational tools were employed: ADMETsar, PASS online, and ProTox. The in silico results indicated acute oral toxicity classes III and IV for the chemical structures of Δ9-tetrahydrocannabinol and cannabidiol, respectively, according to the ADMETsar and ProTox analyses. Additionally, several toxicity endpoints were predicted, including respiratory toxicity, immunotoxicity, and ecotoxicity, among others. An acute oral toxicity test was conducted in an animal model following the OECD Guideline 423 (2001), using a single administration of 2000 mg/kg with a 14-day observation period. Pharmacological screening was performed, and parameters were monitored throughout the 14 days. After euthanasia, blood samples were collected for hematological and biochemical analyses. Macroscopic necropsy and histopathological examinations were also carried out. Regarding acute toxicity, no alterations were observed in hematological and histopathological parameters. The results demonstrate a favorable safety profile for the full-spectrum Cannabis sativa extract enriched with Δ9-THC and CBD, supporting its potential for controlled therapeutic applications. This research provides a scientific basis for the regulation of cannabis-based products in Brazil, contributing to clinical and regulatory decisionmaking by ANVISA.
publishDate 2025
dc.date.none.fl_str_mv 2025-12-02
2025-08-26
2026-01-26T10:25:05Z
2026-01-26T10:25:05Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://repositorio.ufpb.br/jspui/handle/123456789/37424
url https://repositorio.ufpb.br/jspui/handle/123456789/37424
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv Attribution-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nd/3.0/br/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NoDerivs 3.0 Brazil
http://creativecommons.org/licenses/by-nd/3.0/br/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Farmacologia
Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos
UFPB
publisher.none.fl_str_mv Universidade Federal da Paraíba
Brasil
Farmacologia
Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos
UFPB
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFPB
instname:Universidade Federal da Paraíba (UFPB)
instacron:UFPB
instname_str Universidade Federal da Paraíba (UFPB)
instacron_str UFPB
institution UFPB
reponame_str Repositório Institucional da UFPB
collection Repositório Institucional da UFPB
repository.name.fl_str_mv Repositório Institucional da UFPB - Universidade Federal da Paraíba (UFPB)
repository.mail.fl_str_mv diretoria@ufpb.br||bdtd@biblioteca.ufpb.br
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