Epilepsy and cannabidiol - a new perspective for seizures treatment
DOI:
https://doi.org/10.12775/JEHS.2021.11.08.023Keywords
cannabidiol, epilepsy, childrenAbstract
BACKGROUND: Despite the fact that the number of antiepileptic drugs is constantly increasing, epilepsy can still be a therapeutic challenge. Approximately one-third of patients with epilepsy have persistent seizures refractory to treatment. The limited number of effective alternatives motivates researchers to seek new solutions. There is some hope for cannabidiol (CBD) preparations.
AIM OF THE STUDY: The purpose of this study was to review the most recent available literature on the use of cannabidiol in the treatment of refractory epilepsy in children and adults. For this purpose, the PubMed and Google Scholar databases were reviewed. The phrase "cannabidiol and epilepsy" was used to search the database. After Screening titles and abstracts a total of 19 papers and articles cited in them were received and analyzed in detail. RESULTS: Nowadays there are many CBD related products available in the market, Cannabis sativa and Cannabis indica are the plants used due to their strong therapeutic effects and also seizure control. Regulations regarding the use of raw marijuana, cannabis extracts, and cannabinoid-based drugs vary from place to place. Many studies have been generated on the efficacy of cannabinoid therapy in the treatment of epilepsy. This therapy in patients with Dravet syndrome and Lennox-Gaust syndrome results in a reduction in the frequency of motor and total seizures. The most commonly reported side effects of CBD are drowsiness, seizures and diarrhea, but the therapy is generally well tolerated.
SUMMARY AND CONCLUSIONS: Many available studies support the efficacy of CBD as a treatment option to reduce seizure frequency in children with drug-resistant epilepsy, particularly in patients with Dravet and Lennox-Gastaut syndrome. However, there is a lack of reports on the use of CBD in the adult population, which may be an area for further research.
References
Russ SA, Larson K, Halfon N. A national profile of childhood epilepsy and seizure disorder. Pediatrics. 2012;129(2):256-264. doi:10.1542/peds.2010-137.
Kramer U, Nevo Y, Neufeld MY, Fatal A, Leitner Y, Harel S. Epidemiology of epilepsy in childhood: a cohort of 440 consecutive patients. Pediatr Neurol. 1998;18(1):46-50. doi:10.1016/s0887-8994(97)00154-9.
Mitelpunkt A, Kramer U, Hausman Kedem M, et al. The safety, tolerability, and effectiveness of PTL-101, an oral cannabidiol formulation, in pediatric intractable epilepsy: A phase II, open-label, single-center study. Epilepsy Behav. 2019;98(Pt A):233-237. doi:10.1016/j.yebeh.2019.07.007.
Cheung KAK, Peiris H, Wallace G, Holland OJ, Mitchell MD. The Interplay between the Endocannabinoid System, Epilepsy and Cannabinoids. Int J Mol Sci. 2019 Dec 2;20(23):6079. doi: 10.3390/ijms20236079.
Wheless JW, Dlugos D, Miller I, Oh DA, Parikh N, Phillips S, Renfroe JB, Roberts CM, Saeed I, Sparagana SP, Yu J, Cilio MR; INS011-14-029 Study Investigators. Pharmacokinetics and Tolerability of Multiple Doses of Pharmaceutical-Grade Synthetic Cannabidiol in Pediatric Patients with Treatment-Resistant Epilepsy. CNS Drugs. 2019 Jun;33(6):593-604. doi: 10.1007/s40263-019-00624-4.
Laux LC, Bebin EM, Checketts D, Chez M, Flamini R, Marsh ED, Miller I, Nichol K, Park Y, Segal E, Seltzer L, Szaflarski JP, Thiele EA, Weinstock A; CBD EAP study group. Long-term safety and efficacy of cannabidiol in children and adults with treatment resistant Lennox-Gastaut syndrome or Dravet syndrome: Expanded access program results. Epilepsy Res. 2019 Aug;154:13-20. doi: 10.1016/j.eplepsyres.2019.03.015.
Abuhasira R, Shbiro L, Landschaft Y. Medical use of cannabis and cannabinoids containing products - Regulations in Europe and North America. Eur J Intern Med. 2018 Mar;49:2-6. doi: 10.1016/j.ejim.2018.01.001.
Abu-Sawwa R, Scutt B, Park Y. Emerging Use of Epidiolex (Cannabidiol) in Epilepsy. J Pediatr Pharmacol Ther. 2020;25(6):485-499. doi: 10.5863/1551-6776-25.6.485.
Arzimanoglou A, Brandl U, Cross JH, Gil-Nagel A, Lagae L, Landmark CJ, Specchio N, Nabbout R, Thiele EA, Gubbay O, The Cannabinoids International Experts Panel; Collaborators. Epilepsy and cannabidiol: a guide to treatment. Epileptic Disord. 2020 Feb 1;22(1):1-14. doi: 10.1684/epd.2020.1141.
Raucci U, Pietrafusa N, Paolino MC, Di Nardo G, Villa MP, Pavone P, Terrin G, Specchio N, Striano P, Parisi P. Cannabidiol Treatment for Refractory Epilepsies in Pediatrics. Front Pharmacol. 2020 Sep 29;11:586110. doi: 10.3389/fphar.2020.586110.
Dalton WS, Martz R, Lemberger L, Rodda BE, Forney RB. Influence of cannabidiol on delta-9-tetrahydrocannabinol effects. Clin Pharmacol Ther. 1976 Mar;19(3):300-9. doi: 10.1002/cpt1976193300.
Karniol IG, Shirakawa I, Kasinski N, Pfeferman A, Carlini EA. Cannabidiol interferes with the effects of delta 9 - tetrahydrocannabinol in man. Eur J Pharmacol. 1974 Sep;28(1):172-7. doi: 10.1016/0014-2999(74)90129-0.
Morano A, Fanella M, Albini M, Cifelli P, Palma E, Giallonardo AT, Di Bonaventura C. Cannabinoids in the Treatment of Epilepsy: Current Status and Future Prospects. Neuropsychiatr Dis Treat. 2020 Feb 7;16:381-396. doi: 10.2147/NDT.S203782.
Millar SA, Stone NL, Bellman ZD, Yates AS, England TJ, O'Sullivan SE. A systematic review of cannabidiol dosing in clinical populations. Br J Clin Pharmacol. 2019 Sep;85(9):1888-1900. doi: 10.1111/bcp.14038.
Press CA, Knupp KG, Chapman KE. Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy. Epilepsy Behav. 2015 Apr;45:49-52. doi: 10.1016/j.yebeh.2015.02.043.
Dravet C, Oguni H. Dravet syndrome (severe myoclonic epilepsy in infancy). Handb Clin Neurol. 2013;111:627-33. doi: 10.1016/B978-0-444-52891-9.00065-8.
Devinsky O, Nabbout R, Miller I, Laux L, Zolnowska M, Wright S, Roberts C. Long-term cannabidiol treatment in patients with Dravet syndrome: An open-label extension trial. Epilepsia. 2019 Feb;60(2):294-302. doi: 10.1111/epi.14628.
Elliott J, DeJean D, Clifford T, Coyle D, Potter BK, Skidmore B, Alexander C, Repetski AE, Shukla V, McCoy B, Wells GA. Cannabis-based products for pediatric epilepsy: A systematic review. Epilepsia. 2019 Jan;60(1):6-19. doi: 10.1111/epi.14608.
Devinsky O, Cross JH, Laux L, Marsh E, Miller I, Nabbout R, Scheffer IE, Thiele EA, Wright S; Cannabidiol in Dravet Syndrome Study Group. Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome. N Engl J Med. 2017 May 25;376(21):2011-2020. doi: 10.1056/NEJMoa1611618.
Miller I, Scheffer IE, Gunning B, Sanchez-Carpintero R, Gil-Nagel A, Perry MS, Saneto RP, Checketts D, Dunayevich E, Knappertz V; GWPCARE2 Study Group. Dose-Ranging Effect of Adjunctive Oral Cannabidiol vs Placebo on Convulsive Seizure Frequency in Dravet Syndrome: A Randomized Clinical Trial. JAMA Neurol. 2020 May 1;77(5):613-621. doi: 10.1001/jamaneurol.2020.0073.
Devinsky O, Patel AD, Thiele EA, Wong MH, Appleton R, Harden CL, Greenwood S, Morrison G, Sommerville K; GWPCARE1 Part A Study Group. Randomized, dose-ranging safety trial of cannabidiol in Dravet syndrome. Neurology. 2018 Apr 3;90(14):e1204-e1211. doi: 10.1212/WNL.0000000000005254.
Elliott J, DeJean D, Clifford T, Coyle D, Potter BK, Skidmore B, Alexander C, Repetski AE, Shukla V, McCoy B, Wells GA. Cannabis-based products for pediatric epilepsy: A systematic review. Epilepsia. 2019 Jan;60(1):6-19. doi: 10.1111/epi.14608.
Schoedel KA, Szeto I, Setnik B, Sellers EM, Levy-Cooperman N, Mills C, Etges T, Sommerville K. Abuse potential assessment of cannabidiol (CBD) in recreational polydrug users: A randomized, double-blind, controlled trial. Epilepsy Behav. 2018 Nov;88:162-171. doi: 10.1016/j.yebeh.2018.07.027.
Chesney E, Oliver D, Green A, Sovi S, Wilson J, Englund A, Freeman TP, McGuire P. Adverse effects of cannabidiol: a systematic review and meta-analysis of randomized clinical trials. Neuropsychopharmacology. 2020 Oct;45(11):1799-1806. doi: 10.1038/s41386-020-0667-2.
Silvestro S, Mammana S, Cavalli E, Bramanti P, Mazzon E. Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials. Molecules. 2019 Apr 12;24(8):1459. doi: 10.3390/molecules24081459.
Aran A, Cayam-Rand D. Medical Cannabis in Children. Rambam Maimonides Med J. 2020 Jan 30;11(1):e0003. doi: 10.5041/RMMJ.10386.
Silva GD, Del Guerra FB, de Oliveira Lelis M, Pinto LF. Cannabidiol in the Treatment of Epilepsy: A Focused Review of Evidence and Gaps. Front Neurol. 2020 Oct 19;11:531939. doi: 10.3389/fneur.2020.531939.
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