{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:37:36Z","timestamp":1791859056010,"version":"4.3.4"},"reference-count":76,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Cannabidiol (CBD) has transitioned from anecdotal use to an evidence-based adjunctive therapy for Lennox\u2013Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex. This review integrates knowledge on CBD\u2019s pharmacology, pharmacokinetics, and clinical implementation, with focus on metabolism, therapeutic drug monitoring (TDM), and clinically relevant interactions with antiseizure medications. CBD exerts CB1\/CB2-independent mechanisms\u2014prominently GPR55 antagonism, TRP-channel desensitization, and adenosine-mediated network dampening\u2014supporting efficacy across heterogeneous seizure phenotypes. Its pharmacokinetic profile is characterized by low and variable oral bioavailability, a pronounced food effect, extensive tissue distribution, and phase I\/II biotransformation to the active 7-hydroxy-CBD and abundant 7-carboxy-CBD, resulting in substantial inter-individual variability and liability for drug\u2013drug interactions. Clinically salient interactions include CYP2C19-mediated elevation of N-desmethylclobazam and increased transaminases in valproate co-therapy. We summarize emerging TDM practices\u2014standardized fed-state trough sampling with paired measurement of CBD and 7-hydroxy-CBD\u2014and discuss how preliminary interpretive ranges can support dose optimization, adherence assessment, and safety surveillance. Practical recommendations emphasize interaction-aware titration within evidence-based dose bands, liver function monitoring, and standardized documentation of formulation and sampling conditions. Future work should align pharmacogenomics with TDM, refine bioavailability through advanced delivery systems, and tighten analytical and product-quality standards to consolidate CBD as a precision-ready component of modern epilepsy care.<\/jats:p>","DOI":"10.3390\/biom15121668","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T13:03:02Z","timestamp":1764594182000},"page":"1668","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Pharmacological and Pharmacokinetic Profile of Cannabidiol in Human Epilepsy: A Review of Metabolism, Therapeutic Drug Monitoring, and Interactions with Antiseizure Medications"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-2010","authenticated-orcid":false,"given":"Ji-Hoon","family":"Na","sequence":"first","affiliation":[{"name":"Departments of Pediatrics, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 135-720, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5838-249X","authenticated-orcid":false,"given":"Young-Mock","family":"Lee","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 135-720, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1056\/NEJMoa1714631","article-title":"Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome","volume":"378","author":"Devinsky","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1111\/epi.18284","article-title":"Pharmacokinetic variability and use of therapeutic drug monitoring of cannabidiol in patients with refractory epilepsy","volume":"66","author":"Saetre","year":"2025","journal-title":"Epilepsia"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wang, X., Zhang, H., Liu, Y., Xu, Y., Yang, B., Li, H., and Chen, L. (2023). An overview on synthetic and biological activities of cannabidiol (CBD) and its derivatives. Bioorg. Chem., 140.","DOI":"10.1016\/j.bioorg.2023.106810"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.1007\/s10787-024-01523-x","article-title":"Exploring the efficacy and safety of cannabidiol in individuals with epilepsy: An umbrella review of meta-analyses and systematic reviews","volume":"32","author":"Abbasi","year":"2024","journal-title":"Inflammopharmacology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e1204","DOI":"10.1212\/WNL.0000000000005254","article-title":"Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome","volume":"90","author":"Devinsky","year":"2018","journal-title":"Neurology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/S0140-6736(18)30136-3","article-title":"Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): A randomised, double-blind, placebo-controlled phase 3 trial","volume":"391","author":"Thiele","year":"2018","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1002\/epi4.12956","article-title":"Consensus panel recommendations for the optimization of EPIDIOLEX(R) treatment for seizures associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex","volume":"9","author":"Wechsler","year":"2024","journal-title":"Epilepsia Open"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1007\/s40263-020-00784-8","article-title":"Expanding the Treatment Landscape for Lennox-Gastaut Syndrome: Current and Future Strategies","volume":"35","author":"Strzelczyk","year":"2021","journal-title":"CNS Drugs"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1152\/physrev.00049.2021","article-title":"Cannabinoid treatments in epilepsy and seizure disorders","volume":"104","author":"Devinsky","year":"2024","journal-title":"Physiol. Rev."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Martinez Naya, N., Kelly, J., Corna, G., Golino, M., Polizio, A.H., Abbate, A., Toldo, S., and Mezzaroma, E. (2024). An Overview of Cannabidiol as a Multifunctional Drug: Pharmacokinetics and Cellular Effects. Molecules, 29.","DOI":"10.3390\/molecules29020473"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Millar, S.A., Stone, N.L., Yates, A.S., and O\u2019Sullivan, S.E. (2018). A Systematic Review on the Pharmacokinetics of Cannabidiol in Humans. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01365"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Borowicz-Reutt, K., Czernia, J., and Krawczyk, M. (2024). CBD in the Treatment of Epilepsy. Molecules, 29.","DOI":"10.3390\/molecules29091981"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1080\/17425255.2024.2329733","article-title":"Cannabidiol: Metabolism and clinical efficacy in epileptic patients","volume":"20","author":"Verrotti","year":"2024","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00213-020-05712-8","article-title":"Cannabidiol: Pharmacology and therapeutic targets","volume":"238","author":"Britch","year":"2021","journal-title":"Psychopharmacology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Castillo-Arellano, J., Canseco-Alba, A., Cutler, S.J., and Leon, F. (2023). The Polypharmacological Effects of Cannabidiol. Molecules, 28.","DOI":"10.3390\/molecules28073271"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1111\/bcp.13710","article-title":"The pharmacokinetics and the pharmacodynamics of cannabinoids","volume":"84","author":"Lucas","year":"2018","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1080\/17425255.2019.1605355","article-title":"Drug-drug interactions between antiepileptics and cannabinoids","volume":"15","author":"Miziak","year":"2019","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1089\/can.2015.0012","article-title":"Human Metabolites of Cannabidiol: A Review on Their Formation, Biological Activity, and Relevance in Therapy","volume":"1","author":"Ujvary","year":"2016","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.ejim.2023.07.029","article-title":"Cannabidiol\u2019s impact on drug-metabolization","volume":"118","author":"Stollberger","year":"2023","journal-title":"Eur. J. Intern. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Nachnani, R., Knehans, A., Neighbors, J.D., Kocis, P.T., Lee, T., Tegeler, K., Trite, T., Raup-Konsavage, W.M., and Vrana, K.E. (2024). Systematic review of drug-drug interactions of delta-9-tetrahydrocannabinol, cannabidiol, and Cannabis. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1282831"},{"key":"ref_21","first-page":"CD003277","article-title":"Treatment of Lennox-Gastaut syndrome","volume":"2013","author":"Hancock","year":"2013","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Raucci, U., Pietrafusa, N., Paolino, M.C., Di Nardo, G., Villa, M.P., Pavone, P., Terrin, G., Specchio, N., Striano, P., and Parisi, P. (2020). Cannabidiol Treatment for Refractory Epilepsies in Pediatrics. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.586110"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Staben, J., Koch, M., Reid, K., Muckerheide, J., Gilman, L., McGuinness, F., Kiesser, S., Oswald, I.W.H., Koby, K.A., and Martin, T.J. (2023). Cannabidiol and cannabis-inspired terpene blends have acute prosocial effects in the BTBR mouse model of autism spectrum disorder. Front. Neurosci., 17.","DOI":"10.3389\/fnins.2023.1185737"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"11S","DOI":"10.1002\/j.1552-4604.2002.tb05998.x","article-title":"Cannabidiol: An overview of some pharmacological aspects","volume":"42","author":"Mechoulam","year":"2002","journal-title":"J. Clin. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Si, J., Sun, L., Qin, Y., Peng, L., Gong, Y., Gao, C., Shen, W., and Li, M. (2024). Cannabinoids improve mitochondrial function in skeletal muscle of exhaustive exercise training rats by inhibiting mitophagy through the PINK1\/PARKIN and BNIP3 pathways. Chem. Biol. Interact., 389.","DOI":"10.1016\/j.cbi.2024.110855"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15A","DOI":"10.1155\/2005\/242516","article-title":"Pharmacokinetics of cannabinoids","volume":"10","author":"McGilveray","year":"2005","journal-title":"Pain. Res. Manag."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1111\/bcp.14038","article-title":"A systematic review of cannabidiol dosing in clinical populations","volume":"85","author":"Millar","year":"2019","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1056\/NEJMoa1611618","article-title":"Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome","volume":"376","author":"Devinsky","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.seizure.2023.09.015","article-title":"Real-world evidence on the use of cannabidiol for the treatment of drug resistant epilepsy not related to Lennox-Gastaut syndrome, Dravet syndrome or Tuberous Sclerosis Complex","volume":"112","author":"Riveros","year":"2023","journal-title":"Seizure"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Iannone, L.F., Arena, G., Battaglia, D., Bisulli, F., Bonanni, P., Boni, A., Canevini, M.P., Cantalupo, G., Cesaroni, E., and Contin, M. (2021). Results From an Italian Expanded Access Program on Cannabidiol Treatment in Highly Refractory Dravet Syndrome and Lennox-Gastaut Syndrome. Front. Neurol., 12.","DOI":"10.3389\/fneur.2021.673135"},{"key":"ref_31","first-page":"CD009258","article-title":"Clobazam monotherapy for focal or generalized seizures","volume":"7","author":"Arya","year":"2018","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1111\/epi.16355","article-title":"Coadministered cannabidiol and clobazam: Preclinical evidence for both pharmacodynamic and pharmacokinetic interactions","volume":"60","author":"Anderson","year":"2019","journal-title":"Epilepsia"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1684\/epd.2019.1123","article-title":"Pharmacology and drug interactions of cannabinoids","volume":"22","author":"Landmark","year":"2020","journal-title":"Epileptic Disord."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Abbotts, K.S., Nguyen, J.D., O\u2019Connor, P., McDonald, M., and Morrison, S.A. (2022). Pharmacokinetics, Interaction with Food, and Influence on CYP3A4 Activity of Oral Cannabidiol Preparations in Humans. Nutrients, 14.","DOI":"10.3390\/nu14102152"},{"key":"ref_35","first-page":"e7","article-title":"Pharmacokinetics of cannabidiol in children with refractory epileptic encephalopathy","volume":"62","author":"Riva","year":"2021","journal-title":"Epilepsia"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1002\/cbdv.200790147","article-title":"Cannabidiol\u2014Recent advances","volume":"4","author":"Mechoulam","year":"2007","journal-title":"Chem. Biodivers."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1111\/epi.16674","article-title":"Clinical implications of trials investigating drug-drug interactions between cannabidiol and enzyme inducers or inhibitors or common antiseizure drugs","volume":"61","author":"Patsalos","year":"2020","journal-title":"Epilepsia"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1002\/cpdd.665","article-title":"A Phase 1, Open-Label, Pharmacokinetic Trial to Investigate Possible Drug-Drug Interactions Between Clobazam, Stiripentol, or Valproate and Cannabidiol in Healthy Subjects","volume":"8","author":"Morrison","year":"2019","journal-title":"Clin. Pharmacol. Drug Dev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1016\/j.lfs.2006.12.032","article-title":"Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes","volume":"80","author":"Watanabe","year":"2007","journal-title":"Life Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2723","DOI":"10.1007\/s11101-024-10001-9","article-title":"A comprehensive update on cannabidiol, its formulations and drug delivery systems","volume":"24","author":"Banerjee","year":"2024","journal-title":"Phytochem. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1111\/j.1528-1167.2008.01561.x","article-title":"Antiepileptic drugs\u2014Best practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies","volume":"49","author":"Patsalos","year":"2008","journal-title":"Epilepsia"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1111\/bcp.14617","article-title":"A Phase I Trial of the Safety, Tolerability and Pharmacokinetics of Cannabidiol Administered as Single-Dose Oil Solution and Single and Multiple Doses of a Sublingual Wafer in Healthy Volunteers","volume":"87","author":"Hosseini","year":"2021","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.seizure.2020.09.010","article-title":"Interaction of cannabidiol with other antiseizure medications: A narrative review","volume":"86","author":"Gilmartin","year":"2021","journal-title":"Seizure"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1111\/epi.16542","article-title":"Does cannabidiol have antiseizure activity independent of its interactions with clobazam? An appraisal of the evidence from randomized controlled trials","volume":"61","author":"Bialer","year":"2020","journal-title":"Epilepsia"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"109210","DOI":"10.1016\/j.yebeh.2023.109210","article-title":"Cannabidiol as an adjuvant treatment in adults with drug-resistant focal epilepsy","volume":"144","author":"Kochen","year":"2023","journal-title":"Epilepsy Behav."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.seizure.2023.05.003","article-title":"Retrospective chart review study of use of cannabidiol (CBD) independent of concomitant clobazam use in patients with Lennox-Gastaut syndrome or Dravet syndrome","volume":"110","author":"Nabbout","year":"2023","journal-title":"Seizure"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1007\/s13311-023-01397-x","article-title":"Lennox-Gastaut Syndrome: Current Treatments, Novel Therapeutics, and Future Directions","volume":"20","author":"Nelson","year":"2023","journal-title":"Neurotherapeutics"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Souza, J.D.R., Pacheco, J.C., Rossi, G.N., de-Paulo, B.O., Zuardi, A.W., Guimaraes, F.S., Hallak, J.E.C., Crippa, J.A., and Dos Santos, R.G. (2022). Adverse Effects of Oral Cannabidiol: An Updated Systematic Review of Randomized Controlled Trials (2020-2022). Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14122598"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"de Camargo, R.W., de Novais Junior, L.R., da Silva, L.M., Meneguzzo, V., Daros, G.C., da Silva, M.G., and de Bitencourt, R.M. (2022). Implications of the endocannabinoid system and the therapeutic action of cannabinoids in autism spectrum disorder: A literature review. Pharmacol. Biochem. Behav., 221.","DOI":"10.1016\/j.pbb.2022.173492"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1111\/epi.17618","article-title":"Seizure-free days as a novel outcome in patients with Lennox-Gastaut syndrome: Post hoc analysis of patients receiving cannabidiol in two randomized controlled trials","volume":"64","author":"Auvin","year":"2023","journal-title":"Epilepsia"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1177\/08830738231185241","article-title":"Caregivers\u2019 Perspectives on the Impact of Cannabidiol (CBD) Treatment for Dravet and Lennox-Gastaut Syndromes: A Multinational Qualitative Study","volume":"38","author":"Marshall","year":"2023","journal-title":"J. Child. Neurol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1007\/s40263-025-01201-8","article-title":"Clinically Meaningful Reduction in Drop Seizures in Patients with Lennox-Gastaut Syndrome Treated with Cannabidiol: Post Hoc Analysis of Phase 3 Clinical Trials","volume":"39","author":"Specchio","year":"2025","journal-title":"CNS Drugs"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s40263-021-00807-y","article-title":"Highly Purified Cannabidiol for Epilepsy Treatment: A Systematic Review of Epileptic Conditions Beyond Dravet Syndrome and Lennox-Gastaut Syndrome","volume":"35","author":"Lattanzi","year":"2021","journal-title":"CNS Drugs"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"e427","DOI":"10.3346\/jkms.2020.35.e427","article-title":"Cannabidiol for Treating Lennox-Gastaut Syndrome and Dravet Syndrome in Korea","volume":"35","author":"Koo","year":"2020","journal-title":"J. Korean Med. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/epi4.13075","article-title":"Refining management strategies for Lennox-Gastaut syndrome: Updated algorithms and practical approaches","volume":"10","author":"Auvin","year":"2025","journal-title":"Epilepsia Open"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s40001-024-01788-6","article-title":"The efficacy and safety of cannabidiol (CBD) in pediatric patients with Dravet Syndrome: A narrative review of clinical trials","volume":"29","author":"Aderinto","year":"2024","journal-title":"Eur. J. Med. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"110171","DOI":"10.1016\/j.yebeh.2024.110171","article-title":"A comprehensive review of evolving treatment strategies for Dravet syndrome: Insights from randomized trials, meta-analyses, real-world evidence, and emerging therapeutic approaches","volume":"162","author":"Samanta","year":"2025","journal-title":"Epilepsy Behav."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"100731","DOI":"10.1016\/j.ebr.2024.100731","article-title":"The use of cannabidiol in patients with Lennox-Gastaut syndrome and Dravet syndrome in the UK Early Access Program: A retrospective chart review study","volume":"29","author":"Eltze","year":"2025","journal-title":"Epilepsy Behav. Rep."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/ane.13351","article-title":"Cannabidiol in conjunction with clobazam: Analysis of four randomized controlled trials","volume":"143","author":"Gunning","year":"2021","journal-title":"Acta Neurol. Scand."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1111\/epi.17274","article-title":"International consensus on diagnosis and management of Dravet syndrome","volume":"63","author":"Wirrell","year":"2022","journal-title":"Epilepsia"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1002\/epi4.12923","article-title":"Comparative efficacy and safety of stiripentol, cannabidiol and fenfluramine as first-line add-on therapies for seizures in Dravet syndrome: A network meta-analysis","volume":"9","author":"Guerrini","year":"2024","journal-title":"Epilepsia Open"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1001\/jamaneurol.2020.4607","article-title":"Add-on Cannabidiol Treatment for Drug-Resistant Seizures in Tuberous Sclerosis Complex: A Placebo-Controlled Randomized Clinical Trial","volume":"78","author":"Thiele","year":"2021","journal-title":"JAMA Neurol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"733","DOI":"10.2147\/NDT.S347327","article-title":"Treatment-resistant epilepsy and tuberous sclerosis complex: Treatment, maintenance, and future directions","volume":"19","author":"Singh","year":"2023","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2694","DOI":"10.1093\/brain\/awad048","article-title":"Epileptogenesis in tuberous sclerosis complex-related developmental and epileptic encephalopathy","volume":"146","author":"Aronica","year":"2023","journal-title":"Brain"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Melas, P.A., Scherma, M., Fratta, W., Cifani, C., and Fadda, P. (2021). Cannabidiol as a Potential Treatment for Anxiety and Mood Disorders: Molecular Targets and Epigenetic Insights from Preclinical Research. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041863"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Schouten, M., Dalle, S., Mantini, D., and Koppo, K. (2023). Cannabidiol and brain function: Current knowledge and future perspectives. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1328885"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1159\/000521683","article-title":"Therapeutic Potential of Cannabis, Cannabidiol, and Cannabinoid-Based Pharmaceuticals","volume":"107","author":"Legare","year":"2022","journal-title":"Pharmacology"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Mlost, J., Bryk, M., and Starowicz, K. (2020). Cannabidiol for Pain Treatment: Focus on Pharmacology and Mechanism of Action. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228870"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e70122","DOI":"10.1002\/brb3.70122","article-title":"Cannabidiol Treatment for Adult Patients with Drug-Resistant Epilepsies: A Real-World Study in a Tertiary Center","volume":"14","author":"Calonge","year":"2024","journal-title":"Brain Behav."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1002\/epi4.12699","article-title":"Real-world data on cannabidiol treatment of various epilepsy subtypes: A retrospective, multicenter study","volume":"8","author":"Kuhne","year":"2023","journal-title":"Epilepsia Open"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Wang, X., Zhu, H., Liu, T., Guo, Z., Zhao, C., He, Z., and Zheng, W. (2024). Comparison of various doses of oral cannabidiol for treating refractory epilepsy indications: A network meta-analysis. Front. Neurol., 15.","DOI":"10.3389\/fneur.2024.1243597"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Chen, L., Sun, Y., Li, J., Liu, S., Ding, H., Wang, G., and Li, X. (2023). Assessing Cannabidiol as a Therapeutic Agent for Preventing and Alleviating Alzheimer\u2019s Disease Neurodegeneration. Cells, 12.","DOI":"10.3390\/cells12232672"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Massey, S., Quigley, A., Rochfort, S., Christodoulou, J., and Van Bergen, N.J. (2024). Cannabinoids and Genetic Epilepsy Models: A Review with Focus on CDKL5 Deficiency Disorder. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms251910768"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2270","DOI":"10.1111\/epi.18025","article-title":"Cannabidiol-enriched oil for adult patients with drug-resistant epilepsy: Prospective clinical and electrophysiological study","volume":"65","author":"Glatt","year":"2024","journal-title":"Epilepsia"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Mason, E.R., and Cummins, T.R. (2020). Differential inhibition of human Nav1.2 resurgent and persistent sodium currents by cannabidiol and GS967. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21072454"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3613","DOI":"10.1038\/s41467-023-39307-6","article-title":"Cannabidiol inhibits Nav channels through two distinct binding sites","volume":"14","author":"Huang","year":"2023","journal-title":"Nat. Commun."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/12\/1668\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T13:31:17Z","timestamp":1764595877000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/15\/12\/1668"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,30]]},"references-count":76,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["biom15121668"],"URL":"https:\/\/doi.org\/10.3390\/biom15121668","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,30]]}}}