Use of cannabis sativa derivatives in the treatment of pediatric epilepsy: an integrative review with a clinical and decisory-making focus
DOI:
https://doi.org/10.55892/jrg.v9i20.3211Keywords:
cannabis, child, epilepsy, neurodevelopment, treatmentAbstract
Introduction: Epilepsy is a neurological condition characterized by neuronal hyperexcitability, resulting in abnormal and recurrent electrical discharges in the brain, with physical, cognitive, and behavioral repercussions. In the pediatric context, it stands out due to the greater vulnerability to the development of refractory forms, especially given the limited response to conventional treatments. In this scenario, the use of Cannabis sativa derivatives, particularly cannabidiol (CBD), has emerged as a promising therapeutic alternative due to its anticonvulsant properties. Objectives: To analyze the factors that influence healthcare professionals' decision-making regarding the use of Cannabis sativa derivatives in the treatment of refractory pediatric epilepsy. Methods: This is a literature review conducted through the analysis of scientific articles in the databases Cochrane, Embase, LILACS, Oasisbr, PubMed, SciELO, Scopus, and Web of Science. The descriptors used were “Cannabis,” “Epilepsy,” “Child,” and “Niño.” Studies published between 2020 and 2025, available in full text, and addressing the medical perspective on the therapeutic use of cannabis in pediatric epilepsy were included. At the end of the screening process, 102 articles were selected to compose the sample, with a predominance of observational studies and literature reviews. Results: The analyzed studies showed that Cannabis sativa extracts, with or without tetrahydrocannabinol (THC), act by modulating the endocannabinoid system, contributing to the reduction in the frequency and intensity of epileptic seizures in children with refractory forms. Additionally, improvements in quality of life and neuropsychomotor development were observed. However, factors such as social stigma, the lack of standardized protocols, and variability in adverse effects represent important challenges for its widespread adoption in clinical practice. Conclusion: Cannabis sativa appears as a promising therapeutic alternative in the management of refractory pediatric epilepsy, with clinical benefits already described in the literature. However, the need for more robust studies to define criteria for use, dosage, and safety still limits its application. Therefore, treatment individualization and further scientific investigation are essential to consolidate its role in the therapeutic approach to pediatric epilepsy.
Downloads
References
ALIEKPEROVA, N.; KOSYACHENKO, K.; KANIURA, O. Perspectives on formation of medical cannabis market in Ukraine based on holistic approach. J Cannabis Res, n. 2, v. 33, 2 out. 2020.
AMIRAV, A. et al. Cannabis and its Cannabinoids Analysis by Gas Chromatography Mass Spectrometry with Cold EI. Journal of Mass Spectrometry, v. 56, n. 6, 19 mar. 2021.
AMMENDOLIA, I. et al. Pharmacovigilance on cannabidiol as an antiepileptic agent. Front Pharmacol, v. 14, p. 1091978, fev. 2023.
ANDERSON, L. L. et al. Interactions between cannabidiol and Δ 9 ‐tetrahydrocannabinol in modulating seizure susceptibility and survival in a mouse model of Dravet syndrome. British Journal of Pharmacology, v. 177, n. 18, p. 4261–4274, 27 jul. 2020.
ANDERSON, L. L. et al. Cannabichromene, Related Phytocannabinoids, and 5-Fluoro-cannabichromene Have Anticonvulsant Properties in a Mouse Model of Dravet Syndrome. ACS Chemical Neuroscience, v. 12, n. 2, p. 330–339, 4 jan. 2021
ANDERSON, L. L. et al. Cannabigerolic acid, a major biosynthetic precursor molecule in cannabis, exhibits divergent effects on seizures in mouse models of epilepsy. British Journal of Pharmacology, 12 ago. 2021.
ARAÚJO, C. M. et al. Percepção dos pais e responsáveis sobre o uso do canabidiol em crianças e adolescentes com epilepsia. Revista Eletrônica Acervo Saúde, v. 15, n. 2, p. e9560, 24 fev. 2022.
ARAÚJO, M.; ALMEIDA, M. B.; ARAÚJO, L. L. N. Mecanismo de ação dos canabinoides: visão geral. BrJP, 10 jul. 2023.
ARNOLD, J. C. et al. The safety and efficacy of low oral doses of cannabidiol: An evaluation of the evidence. Clinical and Translational Science, v. 16, n. 1, 19 out. 2022.
ARZIMANOGLOU, A. et al. Epilepsy and cannabidiol: a guide to treatment. Epileptic Disord, n. 1, v. 22, p. 1-14, fev. 2020.
AKYÜZ, E. et al. Elucidating the Potential Side Effects of Current Anti-Seizure Drugs for Epilepsy. Current Neuropharmacology, v. 19, n. 11, p. 1865–1883, nov. 2021.
BALACHANDRAN, P.; ELSOHLY, M.; HILL, K. P. Cannabidiol Interactions with Medications, Illicit Substances, and Alcohol: a Comprehensive Review. Journal of General Internal Medicine, v. 36, n. 7, 29 jan. 2021.
BEN-ZEEV, B. Epilepsy and cannabis: facing reality. Developmental Med. & Child Neurology, n. 2, v. 64, out. 2021.
BILGE, S.; EKICI, B. CBD-enriched cannabis for autism spectrum disorder: an experience of a single center in Turkey and reviews of the literature. Journal of Cannabis Research, v. 3, n. 1, dez. 2021.
BITENCOURT, R.; TAKAHASHI, R.; CARLINI, E. From an Alternative Medicine to a New Treatment for Refractory Epilepsies: Can Cannabidiol Follow the Same Path to Treat Neuropsychiatric Disorders?. Front Psychiatry., v. 12, p. 638032, 11 fev. 2021.
BOROWICZ-REUTT, K.; KRAWCZYK, M.; CZERNIA, J. Ketogenic Diet in the Treatment of Epilepsy. Nutrients, v. 16, n. 9, p. 1258, 1 jan. 2024.
BRASIL. Agência Nacional de Vigilância Sanitária. Resolução RDC nº 327, de 9 de dezembro de 2019. Dispõe sobre os procedimentos para concessão da autorização sanitária para fabricação e importação, prescrição, comercialização, e fiscalização de produtos de cannabis para fins medicinais. Diário Oficial da União: seção 1, Brasília, DF, 11 dez. 2019.
BRASIL. Ministério da Saúde. Departamento de Informática do Sistema Único de Saúde (DATASUS). Sistema de Informações sobre Hospitalares (SIH/SUS): internações por epilepsia no Brasil, 2008–2025. Brasília: Ministério da Saúde, 2025. Disponível em: http://tabnet.datasus.gov.br. Acesso em: 08 jul. 2025.
BRASIL. Ministério da Saúde. Departamento de Informática do Sistema Único de Saúde (DATASUS). Sistema de Informações sobre Mortalidade (SIM): óbitos por epilepsia segundo sexo e faixa etária, Brasil, 2008–2025. Brasília: Ministério da Saúde, 2025. Disponível em: http://tabnet.datasus.gov.br. Acesso em: 08 jul. 2025.
BRAUN, E. et al. Second-line cannabis therapy in patients with epilepsy. Clinical Neurology and Neurosurgery, v. 227, p. 107638, abr. 2023
BREIJYEH, Z. et al. Cannabis: A Toxin-Producing Plant with Potential Therapeutic Uses. Toxins, v. 13, n. 2, 5 fev. 2021.
BRIGO, F. et al. Anti‐seizure medications for Lennox‐Gastaut syndrome. Cochrane Database Syst Rev., v. 4, p. CD003277, 7 abr. 2021.
CALAPAI, F. et al. Pharmacological Evaluation of Signals of Disproportionality Reporting Related to Adverse Reactions to Antiepileptic Cannabidiol in VigiBase. Pharmaceuticals, v. 16, n. 10, p. 1420–1420, 5 out. 2023.
CALAPAI, F. et al. Pharmacovigilance of unlicensed cannabidiol in European countries. Phytotherapy Research, n. 1, v. 38, p. 74-81, 6 out. 2023.
CAMPOS, M. G. et al. Drug–Cannabinoid Interactions in Selected Therapeutics for Symptoms Associated with Epilepsy, Autism Spectrum Disorder, Cancer, Multiple Sclerosis, and Pain. Pharmaceuticals, v. 17, n. 5, p. 613, 1 maio 2024.
CARABALLO, R. et al. Long-term use of cannabidiol-enriched medical cannabis in a prospective cohort of children with drug-resistant developmental and epileptic encephalopathy. Seizure, v. 95, p. 56–63, fev. 2022.
CARABALLO, R.; VALENZUELA, G. R. Cannabidiol-enriched medical cannabis as add-on therapy in children with treatment-resistant West syndrome: A study of eight patients. Seizure, v. 92, p. 238–243, nov. 2021.
CHHABRA, M. et al. A multi-centre, tolerability study of a cannabidiol-enriched Cannabis Herbal Extract for chronic headaches in adolescents: The CAN-CHA protocol. PLoS ONE, v. 19, n. 9, p. e0290185–e0290185, 20 set. 2024.
DEGASPERIS, S. M.; WEBSTER, R.; POHL, D. Cannabis Treatment in Children with Epilepsy: Practices of Canadian Neurologists. Canadian Journal of Neurological Sciences, v. 47, n. 4, p. 511–518, 1 jul. 2020.
DRUMMOND-MAIN, C. et al. Cannabidiol Impairs Brain Mitochondrial Metabolism and Neuronal Integrity. 15 set. 2022.
DUBOIS, S. et al. A Volumetric Absorptive Microsampling Technique to Monitor Cannabidiol Levels in Epilepsy Patients. Frontiers in Pharmacology, v. 11, 16 nov. 2020.
ELLIOTT, J. et al. Cannabis-based products for pediatric epilepsy: An updated systematic review. Seizure, v. 75, p. 18-22, fev 2020.
ELLIOTT, J. et al. Neurologists’ perspectives on medical cannabis for pediatric drug-resistant epilepsy in Canada: A qualitative interview study. Seizure, v. 78, abr. 2020.
ESPINOSA-JOVEL, C. Cannabinoids in epilepsy: clinical efficacy and pharmacological considerations. Neurología (English Edition), v. 38, n. 1, nov. 2021.
FAZLOLLAHI, A. et al. Adverse Events of Cannabidiol Use in Patients With Epilepsy. JAMA Network Open, v. 6, n. 4, p. e239126–e239126, 3 abr. 2023.
FEHR, F. et al. Caregiver experiences of children living with a diagnosed neurological disability and using medical cannabis. Journal of Child Health Care, p. 13674935251350177, 20 jun. 2025.
FLAMMER, J. et al. Immune Mechanisms in Epileptogenesis: Update on Diagnosis and Treatment of Autoimmune Epilepsy Syndromes. Drugs. 2023 Feb;83(2):135-158.
FORTUNATO, F. et al. Epilepsy, Immunity and Neuropsychiatric Disorders. Current Neuropharmacology, v. 20, 6 jul. 2022.
FRECKELTON, I. Children as voices and images for medicinal cannabis law reform. Monash Bioethics Review, 31 out. 2021.
FUKUDA, M. et al. Vagus Nerve Stimulation Therapy for Drug-Resistant Epilepsy in Children—A Literature Review. Journal of Clinical Medicine, v. 13, n. 3, p. 780–780, 29 jan. 2024.
GANDY, M. et al. Managing depression and anxiety in people with epilepsy: A survey of epilepsy health professionals by the ILAE Psychology Task Force. Epilepsia Open, v. 6, n. 1, p. 127–139, 8 fev. 2021.
GARCIA, J. B. S.; BARBOSA NETO, J. O. Efeitos adversos do uso dos canabinoides: qual o paradigma de segurança? Brazilian Journal Of Pain, 2023.
GASTON, T. E. et al. Final analysis of potential drug–drug interactions between highly purified cannabidiol and anti‐seizure medications in an open‐label expanded access program. Epilepsia Open, 26 ago. 2023
GIBBARD, M. et al. Family attitudes about and experiences with medical cannabis in children with cancer or epilepsy: an exploratory qualitative study. CMAJ Open, v. 9, n. 2, p. E563–E569, abr. 2021.
GIDAL, B. E. et al. Product labeling accuracy and contamination analysis of commercially available cannabidiol product samples. Frontiers in Pharmacology, v. 15, 18 mar. 2024.
GILMARTIN, C. G. S. et al. Interaction of Cannabidiol with Other Antiseizure Medications: A Narrative Review. Seizure, out. 2020.
GUILHOTO, L. M. et al. COVID-19 and epilepsy: How are people with epilepsy in Brazil? Epilepsy & Behavior, v. 122, p. 108115, set. 2021.
HAKAMI, T. Neuropharmacology of Antiseizure Drugs. Neuropsychopharmacol Reports, n. 3, v. 41, p. 336-351, 23 jul. 2021.
HAMEED, H.; NERI, L. C. L.; SCHOELER, N. Barriers and facilitators to starting and staying on Ketogenic Diet Therapy for children with epilepsy: a scoping review. Clinical Nutrition ESPEN, v. 66, p. 465–473, 22 fev. 2025.
HARIDAS, B.; TESTINO, A.; KOSSOFF, E. H. Ketogenic diet therapy for the treatment of pediatric epilepsy. Epileptic Disorders, 12 dez. 2024.
HAYASHIDA, B.; MOURA, C.; LIMA, R. Tratamento para Epilepsia com uso de Canabidiol. Ciências da Saúde, v. 29, 18 jan. 2025.
HO, J. J. Y. et al. Evaluation of potential drug–drug interactions with medical cannabis. Clinical and Translational Science, v. 17, n. 5, 1 maio 2024.
HOLMES, G. L. Drug Treatment of Epilepsy Neuropsychiatric Comorbidities in Children. Pediatric Drugs, 24 nov. 2020.
HUNTSMAN, R. J. et al. Improving the regulation of medical cannabis in Canada to better serve pediatric patients. CMAJ, n. 41, v. 193, p. E1596–E1599, 18 out. 2021.
HUNTSMAN, R. J. et al. Removing barriers to accessing medical cannabis for paediatric patients. Paediatrics and Child Health, 31 mar. 2023.
JAISUPA, N.; ASHTON, M.; BIRGERSSON, S. Cannabidiol metabolism in vitro: the role of antiseizure medications and CYP2C19 genotypes. Xenobiotica: the fate of foreign compounds in biological systems, v. 55, n. 3, p. 246–255, mar. 2025.
JASTRZĄB, A.; JAROCKA-KARPOWICZ, I.; SKRZYDLEWSKA, E. The Origin and Biomedical Relevance of Cannabigerol. International Journal of Molecular Sciences, v. 23, n. 14, p. 7929, 19 jul. 2022.
JEHI, L. Advances in Therapy for Refractory Epilepsy. Annual Review of Medicine, 12 nov. 2025.
JEONG, H. et al. Short-pulsed micro-magnetic stimulation of the vagus nerve. Frontiers in Physiology, v. 13, 7 out. 2022.
KELLY, L. E.; RIEDER, M. J.; FINKELSTEIN, Y. Medical cannabis for children: Evidence and recommendations. Paediatrics & Child Health, v. 29, n. 2, p. 104–112, 5 abr. 2024.
KHALSA, H. J. et al. Review: Cannabinoids as Medicinals. Curr Addict Rep. 07 sep. 2022
KLEIN, P. et al. Suicidality Risk of Newer Antiseizure Medications. JAMA Neurology, 2 ago. 2021.
LANDUCCI, E. et al. Cannabidiol inhibits microglia activation and mitigates neuronal damage induced by kainate in an in-vitro seizure model. Neurobiology of Disease, v. 174, p. 105895, nov. 2022.
LAHMINI, W.; GYAMFI, S. O.; BOURROUS, M. Survey on the management of childhood epilepsy among general practitioners in the area of Marrakech. BMC Pediatrics, v. 23, n. 1, 4 abr. 2023.
LATTANZI, S. et al. Highly Purified Cannabidiol for Epilepsy Treatment: A Systematic Review of Epileptic Conditions Beyond Dravet Syndrome and Lennox–Gastaut Syndrome. CNS Drugs, v. 35, n. 3, p. 265–281, mar. 2021.
LEVADA, L. P. et al. Revisão da literatura sobre o uso da cannabis medicinal no tratamento da epilepsia. Brazilian Journal of Implantology and Health Sciences, v. 6, n. 3, p. 2134–2154, 24 mar. 2024.
LIN, C.-H.; HSIEH, C.-L. Chinese Herbal Medicine for Treating Epilepsy. Frontiers in Neuroscience, v. 15, 2 jul. 2021.
MADEO, G. et al. Update on Cannabidiol Clinical Toxicity and Adverse Effects: a Systematic Review. Current Neuropharmacology, v. 21, 22 mar. 2023.
MANSELL, H. et al. Medical cannabis in schools: The experiences of caregivers. Paediatrics & Child Health, v. 28, n. 2, p. 102–106, 1 maio 2023.
MARCHESE, F. et al. An Open Retrospective Study of a Standardized Cannabidiol Based-Oil in Treatment-Resistant Epilepsy. Cannabis and Cannabinoid Research, v. 7, n. 2, 21 jul. 2020.
MAZURKIEWICZ-BELDZINSKA, M.; ZAWADZKA, M. Use of cannabidiol in the treatment of epilepsy. Neurol Neurochir Pol, n. 1, v. 56, p. 14-20, 2022.
MOREIRA, G. A. et al. Cannabidiol for the treatment of refractory epilepsy in children: a critical review of the literature. Revista Paulista de Pediatria, v. 41, p. e2021197, 2023.
NA, J.-H.; LEE, H.; LEE, Y.-M. Clinical Efficacy and Safety of the Ketogenic Diet in Patients with Genetic Confirmation of Drug-Resistant Epilepsy. Nutrients, v. 17, n. 6, p. 979–979, 11 mar. 2025.
NABBOUT, R; THIELE, A. E. The role of cannabinoids in epilepsy treatment: a critical review of efficacy results from clinical trials. Epileptic Disord, 03 março. 2020.
NELSON, J. A.; KNUPP, K. G. Lennox-Gastaut Syndrome: Current Treatments, Novel Therapeutics, and Future Directions. Neurotherapeutics, v. 20, n. 5, p. 1255–1262, 1 set. 2023.
NGAMPOOPUN, M.; NABANGCHANG, C.; SUWANPAKDEE, P. Survey of local cannabidiol use in parents of children with epilepsy in Thailand: the prevalence, perceptions, and knowledge. Journal of Cannabis Research, v. 4, n. 1, 26 jul. 2022.
OSMAN, M. et al. Decoding epilepsy treatment: A comparative evaluation contrasting cannabidiol pharmacokinetics in adult and paediatric populations. Chemico-Biological Interactions, v. 394, p. 110988, 1 maio 2024.
PAIVA JÚNIOR, W. DE S.; FARIAS, M. R. A eficácia terapêutica da Cannabis no tratamento da Epilepsia: uma revisão sistemática/ The therapeutic efficacy of Cannabis in the treatment of Epilepsy: a systematic review. Brazilian Journal of Development, v. 7, n. 7, p. 70956–70963, 13 jul. 2021.
PAWLIUK, C. et al. Efficacy and safety of paediatric medicinal cannabis use: A scoping review. Paediatr Child Health, 30 de abril. 2020.
PEREIRA, C. DOS S. et al. Uma revisão acerca da epilepsia: sua epidemiologia no mundo e seu tratamento / A review about epilepsy: its epidemiology in the world and its treatment. Brazilian Journal of Health Review, v. 5, n. 3, 7 jun. 2022.
PERRY, C. J. et al. A new mechanism for cannabidiol in regulating the one‐carbon cycle and methionine levels in Dictyostelium and in mammalian epilepsy models. British Journal of Pharmacology, v. 177, n. 4, p. 912–928, 1 fev. 2020.
PERUCCA, E.; WHITE, H. S.; BIALER, M. New GABA-Targeting Therapies for the Treatment of Seizures and Epilepsy: II. Treatments in Clinical Development. CNS Drugs, v. 37, n. 9, p. 781–795, 1 set. 2023.
PRAKASH, V. Effect of Cannabinoids on Electroencephalography of a Child with Lennox–Gastaut Syndrome. Journal of Neurosciences in Rural Practice, v. 11, n. 04, p. 643–645, 11 ago. 2020
RAHIMPOUR, S. et al. Deep brain stimulation and electromagnetic interference. Clinical Neurology and Neurosurgery, v. 203, p. 106577, 1 abr. 2021.
RAUCCI, U. et al. Cannabidiol Treatment for Refractory Epilepsies in Pediatrics. Frontiers in Pharmacology, v. 11, 29 set. 2020.
ROSAL, M. et al. Epilepsia do tipo Ausência: Uma Revisão Bibliográfica dos Mecanismos Fisiopatológicos e Abordagens Terapêuticas. RECIMA21, v. 5, n. 5, e555237, 17 mai. 2024.
SARLO, G. L.; HOLTON, K. F. Brain concentrations of glutamate and GABA in human epilepsy: A review. Seizure, v. 91, p. 213–227, out. 2021.
SENN, L.; CANNAZZA, G.; BIAGINI, G. Receptors and Channels Possibly Mediating the Effects of Phytocannabinoids on Seizures and Epilepsy. Pharmaceuticals (Basel), n. 8, v. 13, p,174, 30 jul. 2020.
SILVA, G. D. DA et al. O uso de Cannabis sativa no tratamento de crianças com epilepsia refratária ao tratamento / The use of Cannabis sativa in the treatment of children with treatment-refractory epilepsy. Brazilian Journal of Health Review, v. 5, n. 2, p. 7653–7660, 26 abr. 2022.
SILVA, G. D. et al. Cannabidiol in the Treatment of Epilepsy: A Focused Review of Evidence and Gaps. Frontiers in Neurology, v. 11, 19 out. 2020.
SOLMI, M. et al. Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies. BMJ, v. 382, n. 382, p. e072348, 30 ago. 2023.
SU, H.-W. et al. Efficacy and safety of herbal medicine combined with acupuncture in pediatric epilepsy treatment: A meta-analysis of randomized controlled trials. PLoS ONE, v. 19, n. 5, p. e0303201–e0303201, 9 maio 2024.
TALWAR, A. et al. Clinical efficacy and safety of cannabidiol for pediatric refractory epilepsy indications: A systematic review and meta-analysis. Experimental Neurology, v. 359, p. 114238, 1 jan. 2023.
VEZZANI, A. et al. Astrocytes in the initiation and progression of epilepsy. Nat Rev Neurol. 2022 Dec;18(12):707-722.
VIVIERS, H. J.; PETZER, A.; GORDON, R. An assessment of solvent residue contaminants related to cannabis-based products in the South African market. Journal of Cannabis Research, v. 4, n. 1, p. 19, 2022.
WALTON, D. et al. Transcranial magnetic stimulation for the treatment of epilepsy. Cochrane Database of Systematic Reviews, v. 2021, n. 4, 22 abr. 2021.
WANG, S. G. et al. Disposition of Oral Cannabidiol-Rich Cannabis Extracts in Children with Epilepsy. Original Research Article, 12 de fev. 2020.
WANG, X. et al. Comparison of various doses of oral cannabidiol for treating refractory epilepsy indications: a network meta-analysis. Frontiers in Neurology, v. 15, 27 jun. 2024.
WELLS, J. et al. Efficacy and Safety of a Ketogenic Diet in Children and Adolescents with Refractory Epilepsy - A Review. Nutrients, v. 12, n. 6, p. 1809, 17 jun. 2020.
WISHART, D. S. et al. Chemical Composition of Commercial Cannabis. Journal of Agricultural and Food Chemistry, v. 72, n. 25, 5 jan. 2024.
YU, C.; DENG, X.; XU, D. Microglia in epilepsy. Neurobiology of Disease, v. 185, p. 106249, 1 set. 2023.
ZARNOWSKA, I. M. Therapeutic Use of the Ketogenic Diet in Refractory Epilepsy: What We Know and What Still Needs to Be Learned. Nutrients, v. 12, n. 9, p. 2616, 27 ago. 2020.
