Highly Purified Cannabidiol for Epilepsy Treatment: A Systematic Review of Epileptic Conditions Beyond Dravet Syndrome and Lennox-Gastaut Syndrome.
Journal
CNS drugs
ISSN: 1179-1934
Titre abrégé: CNS Drugs
Pays: New Zealand
ID NLM: 9431220
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
accepted:
10
03
2021
pubmed:
24
3
2021
medline:
11
1
2022
entrez:
23
3
2021
Statut:
ppublish
Résumé
Cannabidiol (CBD), which is one major constituent of the Cannabis sativa plant, has anti-seizure properties and does not produce euphoric or intrusive side effects. A plant-derived, highly purified CBD formulation with a known and constant composition has been approved by the US Food and Drug Administration for the treatment of seizures associated with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex. In the European Union, the drug has been authorized by the European Medicines Agency for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome, in conjunction with clobazam, and is under regulatory review for the treatment of seizures in patients with tuberous sclerosis complex. This systematic review aimed to summarize the currently available body of knowledge about the use of this US Food and Drug Administration/European Medicines Agency-approved oral formulation of pharmaceutical-grade CBD in patients with epileptic conditions, especially developmental and epileptic encephalopathies other than Dravet syndrome and Lennox-Gastaut syndrome. The relevant studies were identified through MEDLINE and the US National Institutes of Health Clinical Trials Registry in October 2020. There were no date limitations or language restrictions. The following types of studies were included: clinical trials, cohorts, case-control, cross-sectional, clinical series, and case reports. Participants had to meet the following criteria: any sex, any ethnicity, any age, diagnosis of epilepsy, receiving plant-derived, highly purified (> 98% w/w) CBD in a sesame oil-based oral solution for the treatment of seizures. Data extracted from selected records included efficacy, tolerability, and safety outcomes. Five hundred and seventy records were identified by database and trial register searching. Fifty-seven studies were retrieved for detailed assessment, of which 42 were eventually included for the review. The participants of the studies included patients of both pediatric and adult age. Across the trials, purified CBD was administered at dosages up to 50 mg/kg/day. In a randomized double-blind controlled trial in patients with tuberous sclerosis complex, CBD was associated with a significantly greater percent reduction in seizure frequency than placebo over the treatment period. Open-label studies suggested the effectiveness of CBD in the treatment of children and adults presenting with other epilepsy syndromes than those addressed by regulatory trials, including CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes, SYNGAP1 encephalopathy, and epilepsy with myoclonic absences. The most common adverse events observed during treatment with CBD included somnolence, decreased appetite, diarrhea, and increased serum aminotransferases. The currently available data suggest that response to treatment with a highly purified, plant-derived CBD oil-based solution can be seen in patients across a broad range of epilepsy disorders and etiologies. The existing evidence can provide preliminary support for additional research.
Sections du résumé
BACKGROUND
Cannabidiol (CBD), which is one major constituent of the Cannabis sativa plant, has anti-seizure properties and does not produce euphoric or intrusive side effects. A plant-derived, highly purified CBD formulation with a known and constant composition has been approved by the US Food and Drug Administration for the treatment of seizures associated with Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex. In the European Union, the drug has been authorized by the European Medicines Agency for the treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome, in conjunction with clobazam, and is under regulatory review for the treatment of seizures in patients with tuberous sclerosis complex.
OBJECTIVES
This systematic review aimed to summarize the currently available body of knowledge about the use of this US Food and Drug Administration/European Medicines Agency-approved oral formulation of pharmaceutical-grade CBD in patients with epileptic conditions, especially developmental and epileptic encephalopathies other than Dravet syndrome and Lennox-Gastaut syndrome.
METHODS
The relevant studies were identified through MEDLINE and the US National Institutes of Health Clinical Trials Registry in October 2020. There were no date limitations or language restrictions. The following types of studies were included: clinical trials, cohorts, case-control, cross-sectional, clinical series, and case reports. Participants had to meet the following criteria: any sex, any ethnicity, any age, diagnosis of epilepsy, receiving plant-derived, highly purified (> 98% w/w) CBD in a sesame oil-based oral solution for the treatment of seizures. Data extracted from selected records included efficacy, tolerability, and safety outcomes.
RESULTS
Five hundred and seventy records were identified by database and trial register searching. Fifty-seven studies were retrieved for detailed assessment, of which 42 were eventually included for the review. The participants of the studies included patients of both pediatric and adult age. Across the trials, purified CBD was administered at dosages up to 50 mg/kg/day. In a randomized double-blind controlled trial in patients with tuberous sclerosis complex, CBD was associated with a significantly greater percent reduction in seizure frequency than placebo over the treatment period. Open-label studies suggested the effectiveness of CBD in the treatment of children and adults presenting with other epilepsy syndromes than those addressed by regulatory trials, including CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes, SYNGAP1 encephalopathy, and epilepsy with myoclonic absences. The most common adverse events observed during treatment with CBD included somnolence, decreased appetite, diarrhea, and increased serum aminotransferases.
CONCLUSIONS
The currently available data suggest that response to treatment with a highly purified, plant-derived CBD oil-based solution can be seen in patients across a broad range of epilepsy disorders and etiologies. The existing evidence can provide preliminary support for additional research.
Identifiants
pubmed: 33754312
doi: 10.1007/s40263-021-00807-y
pii: 10.1007/s40263-021-00807-y
pmc: PMC8005394
doi:
Substances chimiques
Anticonvulsants
0
Cannabidiol
19GBJ60SN5
Types de publication
Systematic Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
265-281Références
Hirtz D, Thurman DJ, Gwinn-Hardy K, Mohamed M, Chaudhuri AR, Zalutsky R. How common are the “common” neurologic disorders? Neurology. 2007;68:326–37.
pubmed: 17261678
Cagnetti C, Lattanzi S, Foschi N, Provinciali L, Silvestrini M. Seizure course during pregnancy in catamenial epilepsy. Neurology. 2014;83:339–44.
pubmed: 24944265
Lattanzi S, Zaccara G, Giovannelli F, Grillo E, Nardone R, Silvestrini M, et al. Antiepileptic monotherapy in newly diagnosed focal epilepsy: a network meta-analysis. Acta Neurol Scand. 2019;139:33–41.
pubmed: 30194755
Lattanzi S, Cagnetti C, Foschi N, Provinciali L, Silvestrini M. Lacosamide monotherapy for partial onset seizures. Seizure. 2015;27:71–4.
pubmed: 25891931
Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342:314–9.
pubmed: 10660394
Chen Z, Brodie MJ, Liew D, Kwan P. Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs: a 30-year longitudinal cohort study. JAMA Neurol. 2018;75:279–86.
pubmed: 29279892
Laxer KD, Trinka E, Hirsch LJ, Cendes F, Langfitt J, Delanty N, et al. The consequences of refractory epilepsy and its treatment. Epilepsy Behav. 2014;37:59–70.
pubmed: 24980390
Devinsky O, Cilio MR, Cross H, Fernandez-Ruiz J, French J, Hill C, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014;55:791–802.
pubmed: 24854329
pmcid: 4707667
Cilio MR, Thiele EA, Devinsky O. The case for assessing cannabidiol in epilepsy. Epilepsia. 2014;55:787–90.
pubmed: 24854434
Lattanzi S, Brigo F, Trinka E, Zaccara G, Striano P, Del Giovane C, et al. Adjunctive cannabidiol in patients with Dravet syndrome: a systematic review and meta-analysis of efficacy and safety. CNS Drugs. 2020;34:229–41.
pubmed: 32040850
Lattanzi S, Brigo F, Cagnetti C, Trinka E, Silvestrini M. Efficacy and safety of adjunctive cannabidiol in patients with Lennox–Gastaut syndrome: a systematic review and meta-analysis. CNS Drugs. 2018;32:905–16.
pubmed: 30132269
Lattanzi S, Trinka E, Russo E, Striano P, Citraro R, Silvestrini M, et al. Cannabidiol as adjunctive treatment of seizures associated with Lennox–Gastaut syndrome and Dravet syndrome. Drugs Today (Barc). 2019;55:177–96.
pubmed: 30938373
ClinicalTrials.gov. A randomized controlled trial of cannabidiol (GWP42003-P, CBD) for seizures in tuberous sclerosis complex (GWPCARE6). ClinicalTrials.gov identifier: NCT02544763. 2020. https://clinicaltrials.gov/ct2/show/NCT02544763 . Accessed Oct 2020.
ClinicalTrials.gov. Trial of cannabidiol (CBD; GWP42003-P) for infantile spasms (GWPCARE7). ClinicalTrials.gov identifier: NCT02953548. 2020. https://clinicaltrials.gov/ct2/show/NCT02953548 . Accessed Oct 2020.
ClinicalTrials.gov. Phase 3 trial of cannabidiol (CBD; GWP42003-P) for infantile spasms: open-label extensionpPhase (GWPCARE7). ClinicalTrials.gov identifier: NCT02954887. 2020. https://clinicaltrials.gov/ct2/show/NCT02954887 . Accessed Oct 2020.
Saade D, Joshi C. Pure cannabidiol in the treatment of malignant migrating partial seizures in infancy: a case report. Pediatr Neurol. 2015;52:544–7.
pubmed: 25882081
Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015;56:1246–51.
pubmed: 26114620
Devinsky O, Marsh E, Friedman D, Thiele E, Laux L, Sullivan J, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. 2016;15:270–8.
pubmed: 26724101
Gofshteyn JS, Wilfong A, Devinsky O, Bluvstein J, Charuta J, Ciliberto MA, et al. Cannabidiol as a potential treatment for febrile infection-related epilepsy syndrome (FIRES) in the acute and chronic phases. J Child Neurol. 2017;32:35–40.
pubmed: 27655472
Hess EJ, Moody KA, Geffrey AL, Pollack SF, Skirvin LA, Bruno PL, et al. Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex. Epilepsia. 2016;57:1617–24.
pubmed: 27696387
Kaplan EH, Offermann EA, Sievers JS, Comi AM. Cannabidiol treatment for refractory seizures in Sturge-Weber syndrome. Pediatr Neurol. 2017;71(18–23):e2.
Rosenberg EC, Louik J, Conway E, Devinsky O, Friedman D. Quality of life in childhood epilepsy in pediatric patients enrolled in a prospective, open-label clinical study with cannabidiol. Epilepsia. 2017;58:e96-100.
pubmed: 28617940
pmcid: 5568670
Gaston TE, Bebin EM, Cutter GR, Liu Y, Szaflarski JP. UAB CBD Program. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017;58:1586–92.
Warren PP, Bebin EM, Nabors LB, Szaflarski JP. The use of cannabidiol for seizure management in patients with brain tumor-related epilepsy. Neurocase. 2017;23:287–91.
pubmed: 29063814
Grayson L, Vines B, Nichol K, Szaflarski JP. UAB CBD Program. An interaction between warfarin and cannabidiol, a case report. Epilepsy Behav Case Rep. 2017;9:10–1.
Szaflarski JP, Bebin EM, Comi AM, Patel AD, Joshi C, Checketts D, et al. CBD EAP Study Group. Long-term safety and treatment effects of cannabidiol in children and adults with treatment-resistant epilepsies: expanded access program results. Epilepsia. 2018;59:1540–8.
Devinsky O, Verducci C, Thiele EA, Laux LC, Patel DA, Filloux F, et al. Open-label use of highly purified CBD (Epidiolex®) in patients with CDKL5 deficiency disorder and Aicardi, Dup15q, and Doose syndromes. Epilepsy Behav. 2018;86:131–7.
pubmed: 30006259
Chen KA, Farrar M, Cardamone M, Gill D, Smith R, Cowell CT, et al. Cannabidiol for treating drug-resistant epilepsy in children: the New South Wales experience. Med J Aust. 2018;209:217–21.
pubmed: 30092753
Szaflarski JP, Bebin EM, Cutter G, De Wolfe J, Dure LS, Gaston TE, et al. UAB CBD Program. Cannabidiol improves frequency and severity of seizures and reduces adverse events in an open-label add-on prospective study. Epilepsy Behav. 2018;87:131–6.
Sands TT, Rahdari S, Oldham MS, Nunes EC, Tilton N, Cilio MR. Long-term safety, tolerability, and efficacy of cannabidiol in children with refractory epilepsy: results from an expanded access program in the US. CNS Drugs. 2019;33:47–60.
pubmed: 30460546
Rajaraman RR, Sankar R, Hussain SA. Successful use of pure cannabidiol for the treatment of super-refractory status epilepticus. Epilepsy Behav Case Rep. 2018;10:141–4.
pubmed: 30596011
pmcid: 6306515
Gaston TE, Szaflarski M, Hansen B, Bebin EM, Szaflarski JP. UAB CBD Program. Quality of life in adults enrolled in an open-label study of cannabidiol (CBD) for treatment-resistant epilepsy. Epilepsy Behav. 2019;95:10–7.
Leino AD, Emoto C, Fukuda T, Privitera M, Vinks AA, Alloway RR. Evidence of a clinically significant drug-drug interaction between cannabidiol and tacrolimus. Am J Transpl. 2019;19:2944–8.
Szaflarski JP, Hernando K, Bebin EM, Gaston TE, Grayson LE, Ampah SB, et al. Higher cannabidiol plasma levels are associated with better seizure response following treatment with a pharmaceutical grade cannabidiol. Epilepsy Behav. 2019;95:131–6.
pubmed: 31048098
Allendorfer JB, Nenert R, Bebin EM, Gaston TE, Grayson LE, Hernando KA, et al. fMRI study of cannabidiol-induced changes in attention control in treatment-resistant epilepsy. Epilepsy Behav. 2019;96:114–21.
pubmed: 31129526
Martin RC, Gaston TE, Thompson M, Ampah SB, Cutter G, Bebin EM, et al. Cognitive functioning following long-term cannabidiol use in adults with treatment-resistant epilepsy. Epilepsy Behav. 2019;97:105–10.
pubmed: 31220785
Gaston TE, Bebin EM, Cutter GR, Ampah SB, Liu Y, Grayson LP, et al. UAB CBD Program. Drug–drug interactions with cannabidiol (CBD) appear to have no effect on treatment response in an open-label Expanded Access Program. Epilepsy Behav. 2019;98(Pt A):201–6.
Savage TE, Sourbron J, Bruno PL, Skirvin LA, Wolper ES, Anagnos CJ, et al. Efficacy of cannabidiol in subjects with refractory epilepsy relative to concomitant use of clobazam. Epilepsy Res. 2020;160:106263.
pubmed: 31923763
Ebrahimi-Fakhari D, Agricola KD, Tudor C, Krueger D, Franz DN. Cannabidiol elevates mechanistic target of rapamycin inhibitor levels in patients with tuberous sclerosis complex. Pediatr Neurol. 2020;105:59–61.
pubmed: 31924480
Poisson K, Wong M, Lee C, Cilio MR. Response to cannabidiol in epilepsy of infancy with migrating focal seizures associated with KCNT1 mutations: an open-label, prospective, interventional study. Eur J Paediatr Neurol. 2020;25:77–81.
pubmed: 31926846
Herlopian A, Hess EJ, Barnett J, Geffrey AL, Pollack SF, Skirvin L, et al. Cannabidiol in treatment of refractory epileptic spasms: an open-label study. Epilepsy Behav. 2020;106:106988.
pubmed: 32169600
Sharma AA, Nenert R, Allendorfer JB, Gaston TE, Grayson LP, Hernando K, et al. A preliminary study of the effects of cannabidiol (CBD) on brain structure in patients with epilepsy. Epilepsy Behav Rep. 2019;12:100341.
pubmed: 32322816
pmcid: 7170322
Ben-Menachem E, Gunning B, Cabrera CMA, Van Landingham K, Crockett J, Critchley D, et al. A phase II randomized trial to explore the potential for pharmacokinetic drug-drug interactions with stiripentol or valproate when combined with cannabidiol in patients with epilepsy. CNS Drugs. 2020;34:661–72.
pubmed: 32350749
pmcid: 7275018
Barnett JR, Grinspoon RA, Harisinghani M, Caruso PA, Thiele EA. The efficacy of cannabidiol on renal angiomyolipoma and subependymal giant cell tumor volume in tuberous sclerosis complex. J Clin Neurosci. 2020;77:85–8.
pubmed: 32409220
Gupta S, Schwab M, Valdez-Gonzalez K, Segal E. Rare homozygous nonsense variant in AIMP1 causing early onset epileptic encephalopathy with burst Ssuppression (EOEE-BS). Eur J Med Genet. 2020;63:103970.
pubmed: 32531460
McNamara NA, Dang LT, Sturza J, Ziobro JM, Romanowski EMF, Smith GC, et al. Thrombocytopenia in pediatric patients on concurrent cannabidiol and valproic acid. Epilepsia. 2020;61:e85–9.
pubmed: 32614070
Van Landingham KE, Crockett J, Taylor L, Morrison G. A phase 2, double-blind, placebo-controlled trial to investigate potential drug-drug interactions between cannabidiol and clobazam. J Clin Pharmacol. 2020;60:1304–13.
ClinicalTrials.gov. An open-label extension study to investigate possible drug-drug interactions between clobazam and cannabidiol. ClinicalTrials.gov identifier: NCT02564952. 2020. https://clinicaltrials.gov/ct2/show/NCT02564952 . Accessed Oct 2020.
Nenert R, Allendorfer JB, Bebin EM, Gaston TE, Grayson LE, Houston JT, et al. Cannabidiol normalizes resting-state functional connectivity in treatment-resistant epilepsy. Epilepsy Behav. 2020;112:107297.
pubmed: 32745959
Thompson MD, Martin RC, Grayson LP, Ampah SB, Cutter G, Szaflarski JP, et al. Cognitive function and adaptive skills after a one-year trial of cannabidiol (CBD) in a pediatric sample with treatment-resistant epilepsy. Epilepsy Behav. 2020;111:107299.
pubmed: 32759071
Gaston TE, Allendorfer JB, Nair S, Bebin EM, Grayson LP, Martin RC, et al. UAB CBD Program. Effects of highly purified cannabidiol (CBD) on fMRI of working memory in treatment-resistant epilepsy. Epilepsy Behav. 2020;112:107358.
D’Onofrio G, Kuchenbuch M, Hachon-Le Camus C, Desnous B, Staath V, Napuri S, et al. Slow titration of cannabidiol add-on in drug-resistant epilepsies can improve safety with maintained efficacy in an open-label study. Front Neurol. 2020;11:829.
pubmed: 32903409
pmcid: 7434926
Kuchenbuch M, D’Onofrio G, Chemaly N, Barcia G, Teng T, Nabbout R. Add-on cannabidiol significantly decreases seizures in 3 patients with SYNGAP1 developmental and epileptic encephalopathy. Epilepsia Open. 2020;5:496–500.
pubmed: 32913957
pmcid: 7469777
Cortopassi J. Warfarin dose adjustment required after cannabidiol initiation and titration. Am J Health Syst Pharm. 2020;77:1846–51.
pubmed: 33016308
Bellon M, Walker C, Peterson C. Seizure-related injuries and hospitalizations: self-report data from the 2010 Australian Epilepsy Longitudinal Survey. Epilepsy Behav. 2013;26:7–10.
pubmed: 23201608
Cortright DN, Szallasi A. Biochemical pharmacology of the vanilloid receptor TRPV1. Eur J Biochem. 2004;271:1814–9.
pubmed: 15128291
Sun F-J, Guo W, Zheng D-H, Zhang C-Q, Li S, Liu S-Y, et al. Increased expression of TRPV1 in the cortex and hippocampus from patients with mesial temporal lobe epilepsy. J Mol Neurosci. 2013;49:182–93.
pubmed: 22936245
Lattanzi S, Trinka E, Striano P, Zaccara G, Del Giovane C, Nardone R, et al. Cannabidiol efficacy and clobazam status: a systematic review and meta-analysis. Epilepsia. 2020;61:1090–8.
pubmed: 32452532
Lattanzi S, Zaccara G, Russo E, La Neve A, Lodi MAM, Striano P. Practical use of pharmaceutically purified oral cannabidiol in Dravet syndrome and Lennox-Gastaut syndrome. Expert Rev Neurother. 2020. https://doi.org/10.1080/14737175.2021.1834383 (Epub ahead of print).
Skinner CM, Nookaew I, Ewing LE, Wongsurawat T, Jenjaroenpun P, Quick CM, et al. Potential probiotic or trigger of gut inflammation: the Janus-faced nature of cannabidiol-rich cannabis extract. J Diet Suppl. 2020;17:543–60.
pubmed: 32400224
FDA briefing document. Peripheral and central nervous system drugs. Advisory Committee Meeting. April 19, 2018. NDA210365. Cannabidiol. 2018. https://www.fda.gov/media/112565/download . Accessed Dec 2020.
Lattanzi S, Brigo F, Trinka E, Zaccara G, Cagnetti C, Del Giovane C, et al. Efficacy and safety of cannabidiol in epilepsy: a systematic review and meta-analysis. Drugs. 2018;78:1791–804.
pubmed: 30390221
Epidiolex (cannabidiol) oral solution: highlights of prescribing information. 2020. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf . Accessed Dec 2020.
Busaidy NL, Farooki A, Dowlati A, Perentesis JP, Dancey JE, Doyle LA, Brell JM, Siu LL. Management of metabolic effects associated with anticancer agents targeting the PI3K-Akt-mTOR pathway. J Clin Oncol. 2012;30:2919–28.
pubmed: 22778315
pmcid: 3410405
Zaccara G, Giovannelli F, Schmidt D. Placebo and nocebo responses in drug trials of epilepsy. Epilepsy Behav. 2015;43:128–34.
pubmed: 25703333
Press CA, Knupp KG, Chapman KE. Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy. Epilepsy Behav. 2015;45:49–52.
pubmed: 25845492
Jones NA, Glyn SE, Akiyama S, Hill TD, Hill AD, Weston SE, et al. Cannabidiol exerts anti-convulsant effects in animal models of temporal lobe and partial seizures. Seizure. 2012;21:344–52.
pubmed: 22520455
Consroe P, Wolkin A. Cannabidiol-antiepileptic drug comparisons and interactions in experimentally induced seizures in rats. J Pharmacol Exp Ther. 1977;201:26–32.
pubmed: 850145
Scheffer IE, Berkovic S, Capovilla G, Connolly M, French J, Guilhoto L, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;4:512–21.
Logviss K, Krievins D, Purvina S. Characteristics of clinical trials in rare vs. common diseases: a register-based Latvian study. PLoS One. 2018;13:e0194494.
Margolis A, Giuliano C. Making the switch: from case studies to N-of-1 trials. Epilepsy Behav Rep. 2019;12:100336.
pubmed: 31754660
pmcid: 6854058
Ong KS, Carlin JB, Fahey M, Freeman JL, Scheffer IE, Gillam L, et al. Protocol for a single patient therapy plan: a randomised, double-blind, placebo-controlled N-of-1 trial to assess the efficacy of cannabidiol in patients with intractable epilepsy. J Paediatr Child Health. 2020. https://doi.org/10.1111/jpc.15078 (Epub ahead of print).