Avaliação do perfil toxicológico in silico e in vivo de extratos da planta Cannabis sativa L. contendo os fitocanabinoides canabidiol e Δ9-tetraidrocanabinol
| Ano de defesa: | 2025 |
|---|---|
| Autor(a) principal: | |
| Orientador(a): | |
| Banca de defesa: | |
| 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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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 |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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publishedVersion |
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https://repositorio.ufpb.br/jspui/handle/123456789/37424 |
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https://repositorio.ufpb.br/jspui/handle/123456789/37424 |
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por |
| language |
por |
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Attribution-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nd/3.0/br/ info:eu-repo/semantics/openAccess |
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Attribution-NoDerivs 3.0 Brazil http://creativecommons.org/licenses/by-nd/3.0/br/ |
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openAccess |
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Universidade Federal da Paraíba Brasil Farmacologia Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos UFPB |
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Universidade Federal da Paraíba Brasil Farmacologia Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos UFPB |
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reponame:Repositório Institucional da UFPB instname:Universidade Federal da Paraíba (UFPB) instacron:UFPB |
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Universidade Federal da Paraíba (UFPB) |
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UFPB |
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Repositório Institucional da UFPB - Universidade Federal da Paraíba (UFPB) |
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