Practical use of pharmaceutically purified oral cannabidiol in Dravet syndrome and Lennox-Gastaut syndrome

References

• Hirtz D, Thurman DJ, Gwinn-Hardy K, et al. How common are the “common” neurologic disorders? Neurology. 2007;68:326–337.
   PubMed Web of Science ®Google Scholar
• Lattanzi S, Zaccara G, Giovannelli F, et al. Antiepileptic monotherapy in newly diagnosed focal epilepsy. A network meta-analysis. Acta Neurol Scand. 2019;139:33–41.
   PubMed Web of Science ®Google Scholar
• Cockerell OC, Johnson AL, Sander JW, et al. Remission of epilepsy: results from the national general practice study of epilepsy. Lancet. 1995;346:140–144.
   PubMed Web of Science ®Google Scholar
• Kwan P, Brodie MJ. Early identification of refractory epilepsy. N Engl J Med. 2000;342:314–319.
   PubMed Web of Science ®Google Scholar
• Catterall WA. Dravet syndrome: a sodium channel interneuronopathy. Curr Opin Physiol. 2018;2:42–50.
   PubMed Web of Science ®Google Scholar
• Claes L, Del-Favero J, Ceulemans B, et al. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet. 2001;68:1327–1332.
   PubMed Web of Science ®Google Scholar
• Nabbout R, Gennaro E, Dalla Bernardina B, et al. Spectrum of SCN1A mutations in severe myoclonic epilepsy of infancy. Neurology. 2003;60:1961–1967.
   PubMed Web of Science ®Google Scholar
• Camfield PR. Definition and natural history of Lennox-Gastaut syndrome. Epilepsia. 2011;52:(Suppl.5):3–9.
   Web of Science ®Google Scholar
• Dulac O, N’ Guyen T. The Lennox-Gastaut syndrome. Epilepsia. 1993;34(Suppl.7):S7–17.
   PubMedGoogle Scholar
• Asadi-Pooya AA. Lennox-Gastaut syndrome: a comprehensive review. Neurol Sci. 2018;39:403–414.
   PubMed Web of Science ®Google Scholar
• Perucca E. Cannabinoids in the treatment of epilepsy: hard evidence at last? J Epilepsy Res. 2017;7:61–76.
   PubMedGoogle Scholar
• Franco V, Perucca E. Pharmacological and therapeutic properties of cannabidiol for epilepsy. Drugs. 2019;79:1435–1454.
   PubMed Web of Science ®Google Scholar
• Ibeas Bih C, Chen T, Nunn AV, et al. Molecular targets of cannabidiol in neurological disorders. Neurotherapeutics. 2015;12:699–730.
   PubMed Web of Science ®Google Scholar
• Lattanzi S, Brigo F, Trinka E, et al. Adjunctive cannabidiol in patients with Dravet syndrome: a systematic review and meta-analysis of efficacy and safety. CNS Drugs. 2020;34:229–241.
   PubMed Web of Science ®Google Scholar
• Lattanzi S, Brigo F, Cagnetti C, et al. Efficacy and safety of adjunctive cannabidiol in patients with Lennox-Gastaut syndrome: a systematic review and meta-analysis. CNS Drugs. 2018;32:905–916.
   PubMed Web of Science ®Google Scholar
• FDA. Drug approval package: epidiolex (cannabidiol), NDA 210365, FDA center for drug evaluation and research. [cited Jul 2020]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210365Orig1s000TOC.cfm.
   Google Scholar
• European Medicines Agency. Assessment report: epidyolex. International non-proprietary name: cannabidiol. [cited Jul 2020]. Available from: https://www.ema.europa.eu/en/documents/assessment-report/epidyolex-epar-public-assessment-report_en.pdf.
   Google Scholar
• Devinsky O, Nabbout R, Miller I, et al. Long-term cannabidiol treatment in patients with Dravet syndrome: an open-label extension trial. Epilepsia. 2019;60:294–302.
   PubMed Web of Science ®Google Scholar
• Marsh ED, Mazurkiewicz-Beldzinska M, Halford JJ, et al. Maintained safety and efficacy of cannabidiol (CBD) in a long-term open-label trial in patients with Lennox–Gastaut syndrome (LGS) (GWPCARE 5) [abstract no. 2.271]. The American Epilepsy Society Annual Meeting; 1-5 December 2017; Washington, DC. [cited Jul 2020]. Available from: https://www.aesnet.org/meetings_events/annual_meeting_abstracts/view/344387.
   Google Scholar
• Laux LC, Bebin EM, Checketts D, et al. 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;154:13–20.
   PubMed Web of Science ®Google Scholar
• Taylor L, Gidal B, Blakey G, et al. A phase I, randomized, double-blind, placebo-controlled, single ascending dose, multiple dose, and food effect trial of the safety, tolerability and pharmacokinetics of highly purified cannabidiol in healthy subjects. CNS Drugs. 2018;32:1053–1067.
   PubMed Web of Science ®Google Scholar
• Crockett J, Critchley D, Tayo B, et al. A phase 1, randomized, pharmacokinetic trial of the effect of different meal compositions, whole milk, and alcohol on cannabidiol exposure and safety in healthy subjects. Epilepsia. 2020;61:267–277.
   PubMed Web of Science ®Google Scholar
• Devinsky O, Cilio MR, Cross H, et al. Cannabidiol: pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders. Epilepsia. 2014;55:791–802.
   PubMed Web of Science ®Google Scholar
• Ujváry I, Hanuš L. Human metabolites of cannabidiol: a review on their formation, biological activity, and relevance in therapy. Cannabis Cannabinoid Res. 2016;1:90–101.
   PubMedGoogle Scholar
• Jiang R, Yamaori S, Takeda S, et al. Identification of cytochrome P450 enzymes responsible for metabolism of cannabidiol by human liver microsomes. Life Sci. 2011;89:165–170.
   PubMed Web of Science ®Google Scholar
• Yamaori S, Okamoto Y, Yamamoto I, et al. Cannabidiol, a major phytocannabinoid, as a potent atypical inhibitor for CYP2D6. Drug Metab Dispos. 2011;39:2049–2056.
   PubMed Web of Science ®Google Scholar
• Birnbaum AK, Karanam A, Marino SE, et al. Food effect on pharmacokinetics of cannabidiol oral capsules in adult patients with refractory epilepsy. Epilepsia. 2019;60:1586–1592.
   PubMed Web of Science ®Google Scholar
• Consroe P, Laguna J, Allender J, et al. Controlled clinical trial of cannabidiol in Huntington’s disease. Pharmacol Biochem Behav. 1991;40:701–708.
   PubMed Web of Science ®Google Scholar
• FDA briefing document. Peripheral and central nervous system drugs. Advisory Committee Meeting. NDA210365. Cannabidiol. 2018 Apr 19 [cited Jul 2020]. Available from: https://www.fda.gov/media/112565/download.
   Google Scholar
• Morrison G, Crockett J, Blakey G, et al. A phase 1, open-label, pharmacokinetic trial to investigate possible drug-drug interactions between clobazam, stiripentol, or valproate and cannabidiol in healthy subjects. Clin Pharmacol Drug Dev. 2019;8:1009–1031.
   PubMed Web of Science ®Google Scholar
• Geffrey AL, Pollack SF, Bruno PL, et al. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia. 2015;56:1246–1251.
   PubMed Web of Science ®Google Scholar
• Lattanzi S, Trinka E, Striano P, et al. Cannabidiol efficacy and clobazam status: A systematic review and meta-analysis. Epilepsia. 2020;61:1090–1098.
   PubMed Web of Science ®Google Scholar
• Lattanzi S, Brigo F, Trinka E. Cannabidiol efficacy and clobazam coadministration: where do we stand now? Epilepsia. 2020 Jul 14. Online ahead of print. DOI:10.1111/epi.16607.
   Web of Science ®Google Scholar
• Landmark CJ, Brandl U. Pharmacology and drug interactions of cannabinoids. Epileptic Disord. 2020;22(S1):16–22.
   PubMedGoogle Scholar
• Ben-Menachem E, Gunning B, Arenas Cabrera CM, 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;34:661–672.
   PubMed Web of Science ®Google Scholar
• McNamara NA, Dang LT, Sturza J, et al. Thrombocytopenia in pediatric patients on concurrent cannabidiol and valproic acid. Epilepsia. 2020 Jul 2. Epub ahead of print. DOI:10.1111/epi.16596.
   Web of Science ®Google Scholar
• Morrison G, Taylor L, Crockett J, et al. A phase 1 investigation into the potential effects of cannabidiol on CYP3A4-mediated drug-drug interactions. Abstract presented at AES 2018 (Abst. 1.297). [cited Jul 2020]. Available from: https://www.aesnet.org/sites/default/files/file_attach/AES%20abstract-%20FINAL-low-resolution.pdf.
   Google Scholar
• Gaston TE, Bebin EM, Cutter GR, et al. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia. 2017;58:1586–1592.
   PubMed Web of Science ®Google Scholar
• Klotz KA, Hirsch M, Heers M, et al. Effects of cannabidiol on brivaracetam plasma levels. Epilepsia. 2019;60:e74–e77.
   PubMed Web of Science ®Google Scholar
• Aaberg KM, Bakken IJ, Lossius MI, et al. Comorbidity and childhood epilepsy: a nationwide registry study. Pediatrics. 2016;138:e20160921.
   PubMed Web of Science ®Google Scholar
• Lattanzi S, Brigo F, Trinka E, et al. Efficacy and safety of cannabidiol in epilepsy: a systematic review and meta-analysis. Drugs. 2018;78:1791–1804.
   PubMed Web of Science ®Google Scholar
• Lattanzi S, Trinka E, Russo E, et al. Cannabidiol as adjunctive treatment of seizures associated with Lennox-Gastaut syndrome and Dravet syndrome. Drugs Today (Barc). 2019;55:177–196.
   PubMed Web of Science ®Google Scholar
• Martin RC, Gaston TE, Thompson M, et al. Cognitive functioning following long-term cannabidiol use in adults with treatment-resistant epilepsy. Epilepsy Behav. 2019;97:105–110.
   PubMed Web of Science ®Google Scholar
• Allendorfer JB, Nenert R, Bebin EM, et al. fMRI study of cannabidiol-induced changes in attention control in treatment-resistant epilepsy. Epilepsy Behav. 2019;96:114–121.
   PubMed Web of Science ®Google Scholar
• Skinner CM, Nookaew I, Ewing LE, et al. Potential probiotic or trigger of gut inflammation - the janus-faced nature of cannabidiol-rich cannabis extract. J Diet Suppl. 2020;17:543–560.
   PubMedGoogle Scholar
• Sands TT, Rahdari S, Oldham MS, et al. 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 Web of Science ®Google Scholar
• Epidiolex (cannabidiol) oral solution – highlights of prescribing information. [cited Jul 2020]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210365lbl.pdf.
   Google Scholar
• Cloyd JC, Lackner TE, Leppik IE. Antiepileptics in the elderly. Pharmacoepidemiology and pharmacokinetics. Arch Fam Med. 1994;3:589–598.
   PubMedGoogle Scholar
• Zaccara G, Lattanzi S, Cincotta M, et al. Drug treatments in patients with cardiac diseases and epilepsy. Acta Neurol Scand. 2020;142:37–49.
   PubMed Web of Science ®Google Scholar
• Vandrey R, Raber JC, Raber ME, et al. Cannabinoid dose and label accuracy in edible medical cannabis products. JAMA. 2015;313:2491–2493.
   PubMed Web of Science ®Google Scholar
• Crippa JA, Crippa AC, Hallak JE, et al. Δ9-THC intoxication by cannabidiol-enriched cannabis extract in two children with refractory epilepsy: full remission after switching to purified cannabidiol. Front Pharmacol. 2016;7:359.
   PubMed Web of Science ®Google Scholar
• Thiele E, Bebin M, Bhathal H, et al. Cannabidiol (CBD) treatment in patients with seizures associated with tuberous sclerosis complex: a randomized, double-blind, placebo-controlled phase 3 trial (GWPCARE6) [abstract n. 1.293]. The American Epilepsy Society Annual Meeting; 6-10 December 2019; Baltimore, MD. [cited Jul 2020]. Available from: https://www.aesnet.org/meetings_events/annual_meeting_abstracts/view/2421288.
   Google Scholar
• Devinsky O, Verducci C, Thiele EA, 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;86:131–137.
   PubMed Web of Science ®Google Scholar
• Lattanzi S, Trinka E, Striano P, et al. Cannabidiol oral solution: a new class of antiseizure medications. European Neurological Review. 2020; 15.
   Google Scholar