30DEC

Libyan International Conference for Health Sciences

The First Libyan International Conference for Health Sciences (2024): Open University, Tripoli, Libya
Mediterranean Journal of Pharmacy and Pharmaceutical Sciences
https://app.periodikos.com.br/journal/medjpps/article/doi/10.5281/zenodo.6780458

Mediterranean Journal of Pharmacy and Pharmaceutical Sciences

Review

Unveiling of cannabidiol in the treatment of rare childhood epilepsies: Dravet and Lennox Gastaut syndromes

Mahabba N. Eldernawi, Fadia M. Gafri

http://dx.doi.org/10.5281/zenodo.6780458 Mediterr J Pharm Pharm Sci, vol.2, n2, 5, 2022
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Abstract

In childhood, epilepsy is the most common globally widespread neurological problem, usually with serious consequences for this most critical period of development. Dravet and Lennox Gastaut syndromes are two forms of rare and severe treatment-resistant epilepsies that occur early in life. These resistant epilepsies recognised by continuous unrelenting seizures of many types including the occurrence of status epilepticus. In addition, it is associated with the development of behavioural, neurological, and cognitive deficits and the sequelae of increased risk of mortality rate. Historically, cannabis was found to possess several medical benefits including its use for epilepsy. In this review, information and data were extracted from 99 references using PubMed and Google Scholar (November, 2021). Data with clinical evidence on cannabidiol regarding its efficacy on Dravet syndrome and Lennox Gastaut syndrome, mechanism of action, safety, pharmacokinetic properties and interactions with anti-epileptic medications were all reviewed and discussed. Highly purified cannabidiol is a cannabis-derived compound that is suggested in recent research as an add-on therapy to the existing treatment of both resistant epileptic types; since it can reduce the duration, frequency and severity of seizure disorders. It is also characterised with multiple signalling transduction mechanisms, primarily via the inhibition of excitatory and potentiation of inhibitory pathways. 

Keywords

Antiepileptic drug, cannabidiol, Dravet syndrome, Lennox Gastaut syndrome, mechanism of action, treatment-resistant epilepsies

References

  1. Epilepsy (2021) WHO fact sheets. https://www.who.int/news-room/fact-sheets/detail/epilepsy. Accessed 20th November, 2021.
  2. Janmohamed M, Brodie MJ, Kwan P (2020) Pharmacoresistance - epidemiology, mechanisms, and impact on epilepsy treatment. Neuropharmacology. 168: 107790.  doi: 10.1016/j.neuropharm.2019.107790
  3. Gureshi IA, Mehler MF (2010) Epigenetic mechanisms underlying human epileptic disorders and the process of epileptogenesis. Neurobiology of Disease. 39 (1): 53-60. doi: 10.1016/j.nbd.2010.02.005
  4. Thomson DC (1971) The Johns Hopkins University. The American Review of Canadian Studies. 1 (2): 49-52. doi: 10.1080/02722017109481317
  5. Friedman MJ, Sharieff GQ (2006) Seizures in children. Pediatric Clinics of North America. 53 (2): 257-277. doi: 10.1016/j.pcl.2005.09.010
  6. Sander JW, Shorvon SD (1996) Epidemiology of the epilepsies. Journal of Neurology Neurosurgery and Psychiatry. 61 (5): 433-443. doi: 10.1136/jnnp.61.5.433
  7. Bengleil M, Alzunni F, Shaboun S, Almiahuob M (2022) Hematological consequences of antiepileptic drug therapy among children with epilepsy. Mediterranean Journal of Pharmacy and Pharmaceutical Sciences. 2 (1): 46-54. doi: 10.5281/zenodo.6399498
  8. Smith D, Chadwick D (2001) The management of epilepsy. neurology in practice. Journal of Neurology Neurosurgery and Psychiatry. 70 (IIS): ii15-ii21. doi: 10.1136/jnnp.70.suppl_2.ii15
  9. Uthman BM, Reichl AM, Dean JC, Eisenschenk S, Gilmore R, Reid S, Roper SN, Wilder BJ (2004) Effectiveness of vagus nerve stimulation in epilepsy patients: a 12-year observation. Neurology. 63 (6): 1124-1126. doi: 10.1212/01.WNL.0000138499.87068
  10. Ułamek-Kozioł M, Czuczwar SJ, Januszewski S, Pluta R (2019) Ketogenic diet and epilepsy. Nutrients. 11 (10): E2510. doi: 10.3390/nu11102510
  11. Sankaraneni R, Lachhwani D (2015) Antiepileptic drugs - a review. Pediatric Annals. 44 (2): e36-42. doi: 10.3928/00904481-20150203-10
  12. Macdonald RL, Kelly KM (1993) Antiepileptic drug mechanisms of action. Epilepsia. 34 (S5): S1-S8. doi:  10.1111/j.1528-1157.1993.tb05918.x
  13. Sills G, Rogawski M (2020) Mechanisms of action of currently used antiseizure drugs. Neuropharmacology. 15 (168): 107966. doi: 10.1016/j.neuropharm.2020.107966
  14. Rogawski MA, Taylor CP (2006) Calcium channel α2-δ Subunit, a new antiepileptic drug target. Epilepsy Research. 69 (3): 183-272. doi: 10.1016/j.eplepsyres.2006.03.014
  15. Goldenberg MM (2010) Overview of drugs used for epilepsy and seizures: etiology, diagnosis, and treatment. PT: A peer-reviewed journal for formulary management. 35 (7): 392-415. PMID:20689626.
  16. Jembrek MJ, Vlainic J (2015) GABA Receptors: pharmacological potential and pitfalls. Current Pharmaceutical  Design. 21 (34): 4943-4959. doi: 10.2174/1381612821666150914121624
  17. Meldrum BS (1996) Update on the mechanism of action of antiepileptic drugs. Epilepsia. 37 (6S): S4-S11. doi:. 10.1111/j.1528-1157.1996.tb06038.x
  18. Cowan LD (2002) The epidemiology of the epilepsies in children. Mental Retardation and Developmental Disabilities Research Reviews. 8 (3): 171-181. doi: 10.1002/mrdd.1003
  19. Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, Engel J, French J, Glauser TA, Mathern GW, Moshé SL, Nordli D, Plouin P, Scheffer IE (2010) Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia. 51 (4): 676-685. doi: 10.1111/j.1528-1167.2010.02522.x
  20. Millichap JJ, Koh S, Laux LC, Nordli DR Jr (2009) Child neurology: Dravet syndrome: when to suspect the diagnosis. Neurology. 73 (13): e59-62. doi: 10.1212/WNL.0b013e3181b9c880
  21. Muthugovindan D, Hartman AL (2010) Pediatric epilepsy syndromes. The Neurologist. 16 (4): 223-237. doi: 10.1097/NRL.0b013e3181d9d6b7
  22. Dravet C (2011) The core Dravet syndrome phenotype. Epilepsia. 52 (2S): 3-9. doi: 10.1111/j.1528-1167.2011. 02994.x
  23. Dravet C, Bureau M, Oguni H, Fukuyama Y, Cokar O (2005) Severe myoclonic epilepsy in infancy: dravet syndrome. Advances in Neurology. 95: 71-102. doi: 10.1201/b13560-21
  24. Patra PH, Serafeimidou-Pouliou E, Bazelot M, Whalley BJ, Williams CM, McNeish AJ (2020) Cannabidiol improves survival and behavioural co-morbidities of Dravet syndrome in mice. British Journal of Pharmacology. 177 (12): 2779-2792. doi: 10.1111/bph.15003
  25. Claes L, Del-Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe P (2001) De novo mutations in the the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. American Journal of HumanGenetics. 68 (6): 1327-1332. doi: 10.1086/320609
  26. Harkin LA, McMahon JM, Iona X, Dibbens L, Pelekanos JT, Zuberi SM, Sadleir LG, Andermann E, Gill D, Farrell K, Connolly M, Stanley T, Harbord M, Andermann F, Wang J, Batish SD, Jones JG, Seltzer WK, Gardner A, Infantile Epileptic Encephalopathy Referral Consortium, Sutherland G, Berkovic SF, Mulley JC, Scheffer IE (2007) The spectrum of SCN1A-related infantile epileptic encephalopathies. Brain. 130 (3): 843-852. doi: 10.1093/brain/awm002
  27. Depienne C, Trouillard O, Saint-Martin C, Gourfinkel-An I, Bouteiller D, Carpentier W, Keren B, Abert B, Gautier A, Baulac S, Arzimanoglou A, Cazeneuve C, Nabbout R, LeGuern E (2009)  Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients. Journal of Medical Genetics. 46 (3): 183-191. doi: 10.1136/jmg.2008.062323
  28. Gastraut H, Roger J, Soulayrol R, Tassinari CA, Régis H, Dravet C, Bernard R, Pinsard N, Saint-Jean M (1966) Childhood epileptic encephalopathy with diffuse slow spike-waves (otherwise known as “petit mal variant”) or Lennox syndrome. Epilepsia. 7 (2): 139-179. doi: 10.1111/j.1528-1167.1966.tb06263.x
  29. Asadi-Pooya AA (2018) Lennox-Gastaut syndrome: a comprehensive review. Neurological Sciences. 39 (3): 403-414. doi: 10.1007/s10072-017-3188-y
  30. van Rijckevorsel K (2008) Treatment of Lennox-Gastaut syndrome: overview and recent findings. Neuro-psychiatric Disease and  Treatment. 4 (6): 1001-1019. doi: 10.2147/NDT.S1668
  31. Camfield PR (2011) Definition and natural history of Lennox-Gastaut syndrome. Epilepsia. 52 (5S): 3-9. doi: 10.1111/j.1528-1167.2011.03177.x
  32. Asadi-Pooya AA, Sharifzade M (2012) Lennox-Gastaut syndrome in south Iran: electro-clinical manifestations. Seizure. 21 (10): 760-763. doi: 10.1016/j.seizure.2012.08.003
  33. Goldsmith IL, Zupanc ML, Buchhalter JR (2000) Long-term seizure outcome in 74 patients with Lennox-Gastaut syndrome: effects of incorporating MRI head imaging in defining the cryptogenic subgroup. Epilepsia. 41 (4): 395-399. doi: 10.1111/j.1528-1157.2000.tb00179.x
  34. Cross JH, Auvin S, Falip M, Striano P, Arzimanoglou A (2017) Expert opinion on the management of Lennox-Gastaut syndrome: treatment algorithms and practical considerations. Frontiers in Neurology. 8: 505. doi: 10.3389/fneur.2017.00505
  35. Gallop K, Wild D, Nixon A, Verdian L, Cramer JA (2009) Impact of Lennox-Gastaut syndrome (LGS) on health-related quality of life (HRQL) of patients and caregivers: literature review. Seizure. 18 (8): 554-558. doi:  10.1016/j.seizure.2009.06.005
  36. Amrutkar C, Riel-Romero RM (2020) Lennox Gastaut syndrome. [Updated 2021 Aug 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022. PMID: 30422560.
  37. Sakauchi M, Oguni H, Kato I, Osawa M, Hirose S, Kaneko S, Takahashi Y, Takayama R, Fujiwara T (2011) Mortality in Dravet syndrome: search for risk factors in Japanese patients. Epilepsia. 52 (2S): 50-54. doi:  10.1111/j.1528-1167.2011.03002.x
  38. Cooper MS, Mcintosh A, Crompton DE, McMahon JM, Schneider A, Farrell K, Ganesan V, Gill D, Kivity S, Lerman-Sagie T, McLellan A, Pelekanos J, Ramesh V, Sadleir L, Wirrell E, Scheffer IE (2016) Mortality in Dravet syndrome. Epilepsy Research. 128: 43-47. doi: 10.1016/j.eplepsyres.2016.10.006
  39. Wirrell EC (2016) Treatment of Dravet syndrome. Canadian Journal of Neurological Sciences. 43 (S3): S13-S18. doi: 10.1017/cjn.2016.249
  40. Chiron C (2011) Current therapeutic procedures in Dravet syndrome. Developmental Medicine and Child Neurology. 53 (2S): 16-18. doi: 10.1111/j.1469-8749.2011.03967.x
  41. Stiripentol (Diacomit): For severe myoclonic epilepsy in infancy (Dravet syndrome) (2015) [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health. PMID: 26962599.
  42. Chiron C (2014) Stiripentol for the treatment of Dravet syndrome. Orphan Drugs: Research and Reviews. 4: 29-38. doi: 10.2147/ODRR.S47619
  43. Strzelczyk A, Schubert-Bast S (2021) Expanding the treatment landscape for Lennox-Gastaut syndrome: current and future strategies. CNS Drugs. 35 (1): 61-83. doi: 10.1007/s40263-020-00784-8PMID:33479851
  44. Auvin S (2020) Lennox-Gastaut syndrome: new treatments and treatments under investigation. Revue Neurologique (Paris). 176 (6): 444-447. doi: 10.1016/j.neurol.2020.01.364PMID:32409177
  45. Balagura G, Cacciatore M, Grasso EA, Striano P, Verrotti A (2020) Fenfluramine for the treatment of Dravet syndrome and Lennox-Gastaut syndrome. CNS Drugs. 34 (10): 1001-1007. doi: 10.1007/s40263-020-00755-z
  46. Ragona F, Granata T, Dalla Bernardina B, Offredi F, Darra F, Battaglia D, Morbi M, Brazzo D, Cappelletti S, Chieffo D, De Giorgi I, Fontana E, Freri E, Marini C, Toraldo A, Specchio N, Veggiotti P, Vigevano F, Guerrini R, Guzzetta F, Dravet C (2011) Cognitive development in Dravet syndrome: a retrospective, multicenter study of 26 patients. Epilepsia. 52 (2): 386-392. doi: 10.1111/j.1528-1167.2010.02925.x
  47. Guerrini R, Dravet C, Genton P, Belmonte A, Kaminska A, Dulac O (1998) Lamotrigine and seizure aggravation in severe myoclonic epilepsy. Epilepsia. 39 (5): 508-512. doi: 10.1111/j.1528-1157.1998.tb01413.x
  48. Thanh TN, Chiron C, Dellatolas G, Rey E, Pons G, Vincent J, Dulac O (2002) Efficacité et tolérance à long terme du stiripentol dans le traitement de l’épilepsie myoclonique sévère du nourrisson (syndrome de Dravet). Archives de Pédiatrie. 9 (11): 1120-1127. doi: 10.1016/s0929-693x(02)00090-8
  49. Tassinari CA, Dravet C, Roger J, Cano JP; Gastaut H (1972) Tonic status epilepticus precipitated by intravenous benzodiazepine in five patients with Lennox‐Gastaut syndrome. epilepsia. 13 (3): 421-435. doi:. 10.1111/j.1528 -1157.1972.tb04582.x
  50. Touw M (1981) The religious and medicinal uses of cannabis in China, India and Tibet. Journal of  Psychoactive Drugs. 13 (1): 23-34. doi: 10.1080/02791072.1981.10471447
  51. Zuardi AW (2006) History of cannabis as a medicine: A review. Brazilian Journal of Psychiatry. 28 (2): 153-157. doi: 10.1590/S1516-44462006000200015
  52. Aldrich M (1997) History of therapeutic cannabis. In: Mathre ML ed. Cannabis in medical practice: a legal, historical and pharmacological overview of the therapeutic use of marijuana. Jefferson, NC, London: Mc Farland & Co. ISBN: 0-7964-0361-6.
  53. O’Shaughnessy WB (1843) On the preparations of the Indian hemp, or Gunjah: cannabis indica their effects on the animal system in health, and their utility in the treatment of tetanus and other convulsive diseases. Provincial Medical Journal and Retrospect of the Medical Sciences. 5 (123): 363-369. PMC2490264.
  54. Crocq MA (2020) History of cannabis and the endocannabinoid system. Dialogues in Clinical Neurosciences. 22 (3): 223-228. doi: 10.31887/DCNS.2020.22.3/mcrocq.
  55. Mead A (2019) Legal and regulatory issues governing cannabis and cannabis-derived products in the United States. Frontiers in Plant Science. 10: 697. doi: 10.3389/fpls.2019.00697
  56. U.S. Food and Drug Administration (FDA) News release (2018) [Internet] FDA approves first drug comprised of an active ingredient derived from Marijuana to treat rare, severe forms of epilepsy. [August 2021].
  57. Smith PF (2004)  GW-1000. GW Pharmaceuticals. Current Opinion in Investigational Drugs. 5 (7): 748-754. PMID:15298072.
  58. Sharma P, Murthy P, Bharath MM (2012) Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iranian Journal of  Psychiatry. 7 (4): 149-156. PMID:23408483.
  59. Aizpurua-Olaizola O, Soydaner U, Öztürk E, Schibano D, Simsi Y, Navarro P, Etxebarria N, Usobiagal A (2016) Evolution of the cannabinoid and terpene content during the growth of cannabis sativa plants from different chemotypes. Journal of  Natural Products. 79 (2): 324-331. doi: 10.1021/acs.jnatprod.5b00949
  60. Wong SS, Wilens TE (2017) Medical cannabinoids in children and adolescents: A systematic review. Pediatrics. 140 (5): e20171818. doi: 10.1542/peds.2017-1818
  61. Russo EB, Russo EB (2002) Cannabis and cannabinoids: Pharmacology, toxicology, and therapeutic potential. (1st ed.) Routledge; New York. ISBN: 9780203479506. doi: 10.4324/9780203479506
  62. Pellati F, Borgonetti V, Brighenti V, Biagi M, Benvenuti S, Corsi L (2018) Cannabis sativa L. and nonpsychoactive cannabinoids: Their chemistry and role against oxidative stress, inflammation, and cancer. BioMed Research International. 2018. ID 1691428. doi: 10.1155/2018/1691428
  63. Wilfong A, Cances C, Cross JH, Devinsky O, Marsh E (2018) Cannabidiol (CBD)  reduces seizure frequency in patients with Dravet syndrome who had no response to prior medications: Subgroup analysis of phase 3 study GWPCARE1. American Epilepsy Society. November 6, 2018. doi: Nil.
  64. Blessing EM, Steenkamp MM, Manzanares J, Marmar CR (2015) Cannabidiol as a potential treatment for anxiety disorders. Neurotherapeutics. 12 (4): 825-836. doi: 10.1007/s13311-015-0387-1
  65. Accessdata.fda.gov (2018) Epidiolex prescribing information. [online] available at: https://www.accessdata.fda. gov/drugsatfda_docs/label/2018/210365lbl.pdf> [Accessed 20 August 2021].
  66. Vermersch P (2011) Sativex(®) (tetrahydrocannabinol + cannabidiol), an endocannabinoid system modulator: basic features and main clinical data. Expert Review of Neurotherapeutics. 11 (4S): 15-19. doi: 10.1586/ern. 11.27
  67. Patra PH, Barker-Haliski M, White HS, Whalley BJ, Glyn S, Sandhu H, Jones N, Bazelot M, Williams CM, McNeish AJ (2019) Cannabidiol reduces seizures and associated behavioral comorbidities in a range of animal seizure and epilepsy models. Epilepsia. 60 (2): 303-314. doi: 10.1111/epi.14629
  68. Consroe P, Benedito MA, Leite JR, Carlini EA, Mechoulam R (1982) Effects of cannabidiol on behavioral seizures caused by convulsant drugs or current in mice. European Journal of Pharmacology. 83 (3-4): 293-298. doi: 10.1016/0014-2999(82)90264-3
  69. Kaplan JS, Stella N, Catterall WA, Westenbroek RE (2017) Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome. Proceedings of the National Academy of Sciences of the United States of America. 114 (42): 11229-11234. doi: 10.1073/pnas.1711351114
  70. Miller I, Scheffer IE, Gunning B, Sanchez-Carpintero R, Gil-Nagel A, Perry MS, Saneto RP, Checketts D, Dunayevich E, Knappertz V (2020) GWPCARE2 Study Group. Dose-ranging effect of adjunctive oral cannabidiol vs placebo on convulsive seizure frequency in Dravet syndrome: A randomized clinical trial. JAMA Neurology. 77 (5): 613-621. doi: 10.1001/jamaneurol.2020.0073
  71. Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, Scheffer IE, Thiele EA, Wright S, Cannabidiol in Dravet Syndrome Study Group (2017) Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. The New England Journal of Medicine. 376 (21): 2011-2020. doi: 10.1056/NEJMoa1611618
  72. Koo CM, Kim SH, Lee JS, Park BJ, Lee HK, Kim HD, Kang HC (2020) Cannabidiol for treating Lennox-Gastaut syndrome and Dravet syndrome in Korea. Journal of Korean Medical Science. 35 (50): e427. doi: 10.33
  73. Devinsky O, Patel AD, Cross JH, Villanueva V, Wirrell EC, Privitera M, Greenwood, SM, Roberts C, Checketts D, VanLandingham KE, Zuberi SM; GWPCARE3 Study Group (2018) Effect of cannabidiol on drop seizures in the Lennox-Gastaut syndrome. The New England Journal of Medicine. 378 (20): 1888-1897. doi: 10.1056/ NEJMoa1714631
  74. Thiele E, Marsh E, Mazurkiewicz-Beldzinska M, Halford JJ, Gunning B, Devinsky O, Checketts D, Roberts C (2019) Cannabidiol in patients with Lennox-Gastaut syndrome: interim analysis of an open-label extension study. Epilepsia. 60 (3): 419-428. doi: 10.1111/epi.14670
  75. Brodie JS, Di Marzo V, Guy GW (2015) Polypharmacology shakes hands with complex aetiopathology. Trends in Pharmacological Sciences. 36 (12): 802-821. doi: 10.1016/j.tips.2015.08.010
  76. Seeman P (2016) Cannabidiol is a partial agonist at dopamine D2 High receptors, predicting its antipsychotic clinical dose. Translational Psychiatry. 6 (10): e920. doi: 10.1038/tp.2016.195
  77. Russo EB, Burnett A, Hall B, Parker KK (2005) Agonistic properties of cannabidiol at 5-HT1a receptors. Neurochemical Research. 30 (8): 1037-1043. doi: 10.1007/s11064-005-6978-1
  78. Morano A, Fanella M, Albini M, Cifelli P, Palma E, Giallonardo AT, Di Bonaventura C (2020) Cannabinoids in the treatment of epilepsy: current status and future prospects. Neuropsychiatric Disease and Treatment. 16: 381-396. doi: 10.2147/NDT.S203782
  79. Muller C, Morales P, Reggio PH (2019) Cannabinoid ligands targeting TRP channels. Frontiers in Molecular Neurosciences. 11: 487. doi: 10.3389/fnmol.2018.00487
  80. Zendulka O, Dovrtělová G, Nosková K, Turjap M, Šulcová A, Hanuš L, Juřica J (2016) Cannabinoids and cytochrome P450 interactions. Current Drug Metabolism. 17 (3): 206-226. doi: 10.2174/1389200217666 151210142051
  81. Deutsch DG (2016) A personal retrospective: elevating anandamide (AEA) by targeting fatty acid amide hydrolase (FAAH) and the fatty acid binding proteins (FABPs). Frontiers in Pharmacology. 7: 370. doi: 10.3389 /fphar.2016.00370
  82. Galaj E, Xi ZX (2019) Potential of cannabinoid receptor ligands as treatment for substance use disorders. CNS Drugs. 33 (10): 1001-1030. doi: 10.1007/s40263-019-00664-w
  83. Carrier EJ, Auchampach JA, Hillard CJ (2006) Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression. Proceedings of the National Academy of Sciences of the United States of America. 103 (20): 7895-7900. doi: 10.1073/pnas.0511232103
  84. Castillo A, Tolón MR, Fernández-Ruiz, Romero J, Martinez-Orgado J (2010) The neuroprotective effect of cannabidiol in an in vitro model of newborn hypoxic-ischemic brain damage in mice is mediated by CB(2) and adenosine receptors. Neurobiology of Disease. 37 (2): 434-440. doi: 10.1016/j.nbd.2009.10.023
  85. Hind WH, England TJ, O’Sullivan SE (2016) Cannabidiol protects an in vitro model of the blood-brain barrier from oxygen-glucose deprivation via PPARγ and 5-HT1A receptors. British Journal of Pharmacology. 173 (5): 815-825. doi: 10.1111/bph.13368
  86. Bazelot M, Whalley B (2016) Investigating the involvement of GPR55 signaling in the antiepileptic effects of cannabidiol (P5.244). Neurology. 86 (16S) P5.244. doi: Nil.
  87. Ghovanloo MR, Shuart NG, Mezeyova J, Dean RA, Ruben PC, Goodchild SJ (2018) Inhibitory effects of cannabidiol on voltage-dependent sodium currents. The Journal of Biological Chemistry. 293 (43): 16546-16558. doi: 10.1074/jbc.RA118.004929
  88. Kathmann M, Flau K, Redmer A, Tränkle C, Schlicker E (2006) Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors. Naunyn-Schmiedeberg's Archives of Pharmacology. 372 (5): 354-361. doi: 10.1007/ s00210-006-0033-x
  89. Millar SA, Stone NL, Yates AS, O'Sullivan SE (2018) A systematic review on the pharmacokinetics of cannabidiol in humans. Frontiers in Pharmacology. 9: 1365. doi: 10.3389/fphar.2018.01365
  90. Kis B, Ifrim FC, Buda V, Avram S, Pavel IZ, Antal D, Paunescu V, Dehelean CA, Ardelean F, Diaconeasa Z, Soica C, Danciu C (2019) Cannabidiol-from plant to human body: A promising bioactive molecule with multi-target effects in cancer. International Journal of Molecular Sciences. 20 (23): E5905. doi: 10.3390/ijms 20235905
  91. Johannessen SI, Landmark CJ (2010) Antiepileptic drug interactions - principles and clinical implications. Current Neuropharmacology. 8 (3): 254-267. doi: 10.2174/157015910792246254
  92. Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP; UAB CBD Program (2017) Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 58 (9): 1586-1592. doi: 10.1111/epi.13852
  93. Iffland K, Grotenhermen F (2017) An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies. Cannabis and Cannabinoid Research. 2 (1): 139-154. doi: 10.1089/can.2016.0034
  94. Lattanzi S, Zaccara G, Russo E, La Neve A, Lodi M, Striano P (2021) Practical use of pharmaceutically purified oral cannabidiol in Dravet syndrome and Lennox-Gastaut syndrome. Expert Review of Neurotheapeutics. 21 (1): 99-110. doi: 10.1080/14737175.2021.1834383
  95. Franco V, Perucca E (2019) Pharmacological and therapeutic properties of cannabidiol for epilepsy. Drugs. 79 (13): 1435-1454. doi: 10.1007/s40265-019-01171-4
  96. Lattanzi S, Trinka E, Striano P, Rocchi C, Salvemini S, Silvestrini M, Brigo F (2021) Highly purified cannabidiol for epilepsy treatment: a systematic review of epileptic conditions beyond Dravet syndrome and Lennox-Gastaut syndrome. CNS Drugs. 35 (3): 265-281. doi: 10.1007/s40263-021-00807-y
  97. Chang BS (2018) Cannabidiol and serum antiepileptic drug levels: the ABCs of CBD with AEDs. Epilepsy Currents. 18 (1): 33-34. doi: 10.5698/1535-7597.18.1.33
  98. Abu-Sawwa R, Scutt B, Park Y (2020) Emerging use of epidiolex (Cannabidiol) in epilepsy. The Journal of Pediatric Pharmacology and Therapeutics. 25 (6): 485-499. doi: 10.5863/1551-6776-25.6.48
  99. Epidiolex prices, coupons and patient assistance programs-Drugs.com. https://www.drugs.com/price-guide/ epidiolex. Accessed November 2, 2021.

Submitted date:
02/28/2022

Reviewed date:
05/23/2022

Accepted date:
05/28/2022

Publication date:
11/08/2024

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