The Use of Cannabidiol in the Treatment of Pediatric Refractory Epilepsy: An Integrative Review
DOI:
https://doi.org/10.22479/texturav19n1p15_32Keywords:
Endocannabinoids; Cannabinoids; Cannabidiol; EpilepsyAbstract
Cannabidiol – CBD is a non-psychoactive substance originating from cannabis sativa, which has satisfactory effects in the treatment of epilepsy, a disease characterized as a chronic brain disorder, resulting in an abnormal, excessive, intermittent and self-limited discharge of neurons in a certain area of the brain, with epileptic seizures as its main symptom. This study aims to summarize the randomized clinical trials in Portuguese, English and Spanish, which deal with the use of Cannabidiol in the treatment of epilepsy, published between 2013 and 2023, including those that fit the intended pediatric age. The databases consulted were MEDLINE - PubMed and Scielo using the descriptors “epilepsy”, “cannabis sativa”, “refractory epilepsy” together with the Boolean operator AND to establish the logical relationship between them, using the Randomized Controlled Trial search filter. Cannabidiol has shown to be effective in its pharmacological effects in the treatment of pediatric refractory epilepsy, providing patients with a better quality of life. However, its mechanism of action is not yet fully understood and the side effects caused by the active ingredient are frequent, requiring emphasis on the development of new research related to the long-term use of Cannabidiol.
Downloads
References
Brasil, Agência Nacional de Vigilância Sanitária (ANVISA). Resolução da Diretoria Colegiada RDC No 660, de 30 de março de 2022. Disponível em: https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-660-de-30-de-marco-de-2022-389908959. Acessado em 15 de fevereiro de 2025.
Ben-Zeev, B. Medical Cannabis for Intractable Epilepsy in Childhood: A Review. Rambam Maimonides Medical Journal, v. 11, n. 1, p. e0004, 30 jan. 2020. DOI: https://doi.org/10.5041/RMMJ.10387
Campos, A. C.; Fogaça, M. V.; Scarante, F. F. et al. Plastic and Neuroprotective Mechanisms Involved in the Therapeutic Effects of Cannabidiol in Psychiatric Disorders. Frontiers in Pharmacology, v. 8, p. 269, 2017. DOI: https://doi.org/10.3389/fphar.2017.00269
Casey, S. L.; Atwal, N.; Vaughan, C. W. Cannabis constituent synergy in a mouse neuropathic pain model. PAIN, v. 158, n. 12, p. 2452, dez. 2017. DOI: https://doi.org/10.1097/j.pain.0000000000001051
Conceicao, H. C.; Salino, A. V.; Queiroz, A. K. S. et al. Síndrome de Lennox-Gastaut: relato de caso. Archives Of Health Investigation, v. 6, n. 2, 22 fev. 2017. DOI: https://doi.org/10.21270/archi.v6i2.1805
Oliveira Costa, L. L.; Brandão, E. C.; Segundo, L. M. B. M. Update on epilepsy: literature review. Rev Med, v. 99, n. 2, p. 170–81, 2020. DOI: https://doi.org/10.11606/issn.1679-9836.v99i2p170-181
Devinsky, O.; Cross, J. H.; Laux, L. et al. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. New England Journal of Medicine, v. 376, n. 21, p. 2011–2020, 25 maio 2017. DOI: https://doi.org/10.1056/NEJMoa1611618
Devinsky, O.; Patel, A. D.; Thiele, E. A. at al. Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology, v. 90, n. 14, p. e1204–e1211, 3 abr. 2018a. DOI: https://doi.org/10.1212/WNL.0000000000005254
Devinsky, O. Patel, A. D.; Cross, H. J. et al. Effect of Cannabidiol on Drop Seizures in the Lennox–Gastaut Syndrome. New England Journal of Medicine, v. 378, n. 20, p. 1888–1897, 17 maio 2018b. DOI: https://doi.org/10.1056/NEJMoa1714631
Fernandes De Souza, A. A.; Silva, A. F. M.; Silva, T. F. et al. Cannabis sativa: Uso de fitocanabinóides para o tratamento da dor crônica. Brazilian Journal of Natural Sciences, v. 2, n. 1, p. 20, 11 jan. 2019. DOI: https://doi.org/10.31415/bjns.v2i1.30
Grosso, A. F. Cannabis: de planta condenada pelo preconceito a uma das grandes opções terapêuticas do século. Journal of Human Growth and Development, v. 30, n. 1, p. 94–97, abr. 2020. DOI: https://doi.org/10.7322/jhgd.v30.9977
Hill, K. P. Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems: A Clinical Review. JAMA, v. 313, n. 24, p. 2474–2483, 23 jun. 2015. DOI: https://doi.org/10.1001/jama.2015.6199
Lopes, J. M. Apoio Social e Qualidade de Vida em Pessoas com Epilepsia. Tese-doutorado, Programa de Pós-graduação em Medicina e Saúde Humana. BAHIANA, Bahia, Brasil. 116p. Disponível em: https://repositorio.bahiana.edu.br:8443/jspui/handle/bahiana/76632021. Acessado em 14 de janeiro de 2024.
Lopes, L. A.; Carli, B. P.; Moura, C. S. et al. O Uso de Canabinoides de Cannabis Sativa L. no Tratamento da Epilepsia: Uma Revisão Integrativa. Infarma - Ciências Farmacêuticas, v. 34, n. 1, p. 25–33, 8 abr. 2022. DOI: https://doi.org/10.14450/2318-9312.v34.e1.a2022.pp25-33
MAIA, C.; Moreira, A. R.; Lopes, T. et al. Risk of recurrence after a first unprovoked seizure in children. Jornal de Pediatria, v. 93, p. 281–286, jun. 2017. DOI: https://doi.org/10.1016/j.jped.2016.07.001
Manganelli, L. A. G.; Fonseca, Y. S.; Correia, A. P. et al. Uso Terapêutico de canabinóides no tratamento de epilepsia em crianças no Brasil. Editora Científica Digital, 2020. Disponível em: https://www.editoracientifica.com.br/artigos/uso-terapeutico-de-canabinoides-no-tratamentode-epilepsia-em-criancas-no-brasil Acesso em: 28 out. 2024 DOI: https://doi.org/10.37885/200901519
Matos, R. L. A.; Spinola, L. A.; Barboza, L. L. et al. O Uso do Canabidiol no Tratamento da Epilepsia. Revista Virtual de Química, v. 9, n. 2, 4 mar. 2017.
Mellis, C. Cannabidiol for drug-resistant seizures in the Dravet syndrome. Journal of Paediatrics and Child Health, v. 54, n. 1, p. 101–102, 2018. DOI: https://doi.org/10.1111/jpc.13803
Menezes, C. E. G.; Santos, D. L.; Nery, E. S. et al. Everolimus as a therapeutic option in refractory epilepsy in children with tuberous sclerosis: a systematic review. Arquivos de Neuro-Psiquiatria, v. 81, p. 392–398, 5 jun. 2023. DOI: https://doi.org/10.1055/s-0042-1758442
Miller, I.; Scheffer, I. E.; Gunning, B. et al. Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs Placebo on Convulsive Seizure Frequency in Dravet Syndrome: A Randomized Clinical Trial. JAMA Neurology, v. 77, n. 5, p. 613–621, 1 maio 2020. DOI: https://doi.org/10.1001/jamaneurol.2020.0073
Moreira, G. A.; Neto, R. M.; Ribeiro, R. G. et al. Canabidiol para o tratamento de epilepsia refratária em crianças: uma revisão crítica da literatura. Revista Paulista de Pediatria, v. 41, p. e2021197, 6 jul. 2022. DOI: https://doi.org/10.1590/1984-0462/2023/41/2021197
Oguni, H. Epilepsy with myoclonic-atonic seizures, also known as Doose syndrome: Modification of the diagnostic criteria. European Journal of Paediatric Neurology, v. 36, p. 37–50, 1 jan. 2022. DOI: https://doi.org/10.1016/j.ejpn.2021.11.009
Oshiro, C. A. & Castro, L. H. M. Cannabidiol and epilepsy in Brazil: a current review. Arquivos de Neuro-Psiquiatria, v. 80, p. 182–192, 12 ago. 2022. DOI: https://doi.org/10.1590/0004-282x-anp-2022-s137
Penha, E. M.; Cardoso, D. D. S.; Coelho, L. P. et al. A Regulamentação de Medicamentos Derivados da Cannabis sativa no Brasil. Brazilian Journal of Forensic Sciences, Medical Law and Bioethics, v. 9, n. 1, p. 125–145, 26 dez. 2019. DOI: https://doi.org/10.17063/bjfs9(1)y2019125
Pierro, N. P. A.; Pierro, L. M. C.; Fernandes, S. T. Cannabis: 12.000 anos de experiências e preconceitos. BrJP, v. 6, p. 80–84, 25 set. 2023. DOI: https://doi.org/10.5935/2595-0118.20230055-en
Pittau, F.; Korff, C. M.; Nordli, D. R. Epileptic spasms in epilepsy with myoclonic-atonic seizures (Doose syndrome). Epileptic Disorders: International Epilepsy Journal with Videotape, v. 18, n. 3, p. 289–296, 1 set. 2016. DOI: https://doi.org/10.1684/epd.2016.0854
Porter, B. E. & Jacobson, C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy & Behavior, v. 29, n. 3, p. 574–577, 1 dez. 2013. DOI: https://doi.org/10.1016/j.yebeh.2013.08.037
Rastin, C.; Schenkel, L. C.; Sadikovic, B. Complexity in Genetic Epilepsies: A Comprehensive Review. International Journal of Molecular Sciences, v. 24, n. 14606, 2023. DOI: https://doi.org/10.3390/ijms241914606
Raymundo, P. G. & Souza, P. R. K. Cannabis Sativa L. Os prós e contras do uso terapêutico de uma droga de abuso. Revista Brasileira de Ciências da Saúde, v. 39, n. 3, 2007.
Samanta, D. Management of Lennox-Gastaut syndrome beyond childhood: A comprehensive review. Epilepsy & Behavior, v. 114, 1 jan. 2021. DOI: https://doi.org/10.1016/j.yebeh.2020.107612
Schurman, L. D.; Lu, D.; Kendall, D, A. et al. Molecular Mechanism and Cannabinoid Pharmacology. Substance Use Disorders: From Etiology to Treatment. Cham: Springer International Publishing, 2020. p. 323–353. DOI: https://doi.org/10.1007/164_2019_298
Silva, C. R. A.; Cardoso, I. S. Z. O.; Machado, N. R. Considerações sobre epilepsia. Boletim Científico de Pedriatra, Sociedade de Pediatria do Rio Grande do Sul. v. 2, n. 3, p. 71–76, 2013.
Sirven, J. I. Epilepsy: A Spectrum Disorder. Cold Spring Harbor Perspectives in Medicine, v. 5, n. 9, p. a022848, 9 jan. 2015. DOI: https://doi.org/10.1101/cshperspect.a022848
Thiele, E. A.; Marsh, E. D.; French, J. A. et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet (London, England), v. 391, n. 10125, p. 1085–1096, 17 mar. 2018.
Tzadok, M.; Uliel-Siboni, S.; Linder, I. et al. CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Israeli experience. Seizure, v. 35, p. 41–44, fev. 2016. DOI: https://doi.org/10.1016/j.seizure.2016.01.004
WEYH, A. Aspectos epidemiológicos e moleculares da epilepsia: análise da mortalidade por epilepsia no Brasil e de mecanismos moleculares em um estudo de biologia de sistemas. Tese-doutorado, Programa de Pós-graduação em Medicina: Ciências Médicas, UFRS, Rio Grande do Sul, Brasil. 58p. 2023. Disponível em https://lume.ufrgs.br/handle/10183/265080. Acessado em 23 de outubro de 2024.
Zou, S. & Kumar, U. Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. International Journal of Molecular Sciences, v. 19, n. 3, p. 833, 13 mar. 2018. DOI: https://doi.org/10.3390/ijms19030833
Zuberi, S. M.; Wirrell, E.; Yozawitz, E. et al. ILAE classification and definition of epilepsy syndromes with onset in neonates and infants: Position statement by the ILAE Task Force on Nosology and Definitions. Epilepsia, v. 63, n. 6, p. 1349–1397, 2022. DOI: https://doi.org/10.1111/epi.17239
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Texture
This work is licensed under a Creative Commons Attribution 4.0 International License.
The authors grant copyright on an approved manuscript with exclusive publication for Texture Journal in electronic format, including figures/ illustrations and content for the dissemination of the article, including on the social networks of the Texture Journal.
