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Cannabis for paediatric epilepsy: challenges and conundrums

Kerrie-Anne Chen, Michelle A Farrar, Michael Cardamone and John A Lawson
Med J Aust 2018; 208 (3): . || doi: 10.5694/mja17.00699
Published online: 19 February 2018

Summary

 

  • Research is expanding for the use of cannabidiol as an anticonvulsant drug. The mechanism of cannabidiol in paediatric epilepsy is unclear but is thought to play a role in modulation of synaptic transmission.
  • Evidence for its efficacy in treating epilepsy is limited but growing, with a single pharmaceutical company-funded randomised double-blind controlled trial in children with Dravet syndrome.
  • Progress towards the use of medicinal cannabinoids incorporates a complex interplay of social influences and political and legal reform.
  • Access to unregistered but available cannabidiol in Australia outside of clinical trials and compassionate access schemes is state dependent and will require Therapeutic Goods Administration approval, although the cost may be prohibitive.
  • Further clinical trials are needed to clearly define efficacy and safety, particularly long term.

 


  • 1 Sydney Children's Hospital, Randwick, Sydney, NSW
  • 2 UNSW Sydney, Sydney, NSW



Competing interests:

John Lawson is the lead investigator in the NSW Ministry of Health-funded medical cannabis trials.

  • 1. Szaflarski JP, Bebin EM. Cannabis, cannabidiol, and epilepsy - from receptors to clinical response. Epilepsy Behav 2014; 41: 277-282.
  • 2. Rosenberg EC, Tsien RW, Whalley BJ, et al. Cannabinoids and epilepsy. Neurotherapeutics 2015; 12: 747-768.
  • 3. Schrot RJ, Hubbard JR. Cannabinoids: Medical implications. Ann Med 2016; 48: 128-141.
  • 4. National Academies of Sciences Engineering and Medicine. The health effects of cannabis and cannabinoids: the current state of evidence and recommendations for research. Washington, DC: The National Academies Press, 2017.
  • 5. Sznitman SR, Bretteville-Jensen AL. Public opinion and medical cannabis policies: examining the role of underlying beliefs and national medical cannabis policies. Harm Reduct J 2015; 12: 46.
  • 6. Griffiths M. Medicinal cannabis campaign demands better access to drug. ABC News 2017; 3 Feb. http://www.abc.net.au/news/2017-01-21/medicinal-cannabis-campaign-from-advocates,-epilepsy-australia/8198044 (viewed Dec 2017).
  • 7. Berkovic SF. Cannabinoids for epilepsy — real data, at last. N Engl J Med 2017; 376: 2075-2076.
  • 8. Burstein P. The impact of public opinion on public policy: a review and an agenda. Polit Res Q 2003; 56: 29-40.
  • 9. Grbic J, Goddard P, Ryder D. Observations of the role of science in the United States medical cannabis state policies: lessons learnt. Int J Drug Policy 2017; 42: 109-114.
  • 10. Kwan P, Arzimanoglou A, Berg AT, et al. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia 2010; 51: 1069-1077.
  • 11. Geerts A, Arts WF, Stroink H, et al. Course and outcome of childhood epilepsy: a 15-year follow-up of the Dutch Study of Epilepsy in Childhood. Epilepsia 2010; 51: 1189-1197.
  • 12. Berg a T, Shinnar S, Levy SR, et al. Early development of intractable epilepsy in children: a prospective study. Neurology 2001; 56: 1445-1452.
  • 13. Laxer KD, Trinka E, Hirsch LJ, et al. The consequences of refractory epilepsy and its treatment. Epilepsy Behav 2014; 37: 59-70.
  • 14. 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.
  • 15. Bonn-Miller MO, Loflin MJE, Thomas BF, et al. Labeling accuracy of cannabidiol extracts sold online. JAMA 2017; 318: 1708.
  • 16. Zhornitsky S, Potvin S. Cannabidiol in humans - the quest for therapeutic targets. Pharmaceuticals 2012; 5: 529-552.
  • 17. Thomas A, Baillie GL, Phillips AM, et al. Cannabidiol displays unexpectedly high potency as an antagonist of CB1 and CB2 receptor agonists in vitro. Br J Pharmacol 2007; 150: 613-623.
  • 18. Ibeas Bih C, Chen T, Nunn AVW, et al. Molecular targets of cannabidiol in neurological disorders. Neurotherapeutics 2015; 12: 699-730.
  • 19. Reggio PH, Shore DM. The therapeutic potential of orphan GPCRs, GPR35 and GPR55. Front Pharmacol 2015; 6: 1-22.
  • 20. Gaston TE, Friedman D. Pharmacology of cannabinoids in the treatment of epilepsy. Epilepsy Behav 2017; 70: 313-318.
  • 21. Iannotti FA, Di Marzo V, Petrosino S. Endocannabinoids and endocannabinoid-related mediators: targets, metabolism and role in neurological disorders. Prog Lipid Res 2016; 62: 107-128.
  • 22. Treat L, Chapman KE, Colborn KL, et al. Duration of use of oral cannabis extract in a cohort of pediatric epilepsy patients. Epilepsia 2017; 58: 123-127.
  • 23. Hess EJ, Moody KA, Geffrey AL, et al. Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex. Epilepsia 2016; 57: 1617-1624.
  • 24. Gofshteyn JS, Wilfong A, Devinsky O, 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.
  • 25. Kaplan EH, Offermann EA, Sievers JW, et al. Cannabidiol treatment for refractory seizures in Sturge-Weber syndrome. Pediatr Neurol 2017; 71: 18-23.
  • 26. Tzadok M, Uliel-Siboni S, Linder I, et al. CBD-enriched medical cannabis for intractable pediatric epilepsy: the current Israeli experience. Seizure 2016; 35: 41-44.
  • 27. Hussain SA, Zhou R, Jacobson C, et al. Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: a potential role for infantile spasms and Lennox-Gastaut syndrome. Epilepsy Behav 2015; 47: 138-141.
  • 28. Saade D, Joshi C. Pure cannabidiol in the treatment of malignant migrating partial seizures in infancy: a case report. Pediatr Neurol 2015; 52: 544-547.
  • 29. 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.
  • 30. Porter BE, Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy Behav 2013; 29: 574-577.
  • 31. Maa E, Figi P. The case for medical marijuana in epilepsy. Epilepsia 2014; 55: 783-786.
  • 32. Gloss D, Vickrey B. Cannabinoids for epilepsy. Cochrane Database Syst Rev 2014; (3): CD009270.
  • 33. Devinsky O, Cross JH, Laux L, et al. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med 2017; 376: 2011-2020.
  • 34. Tang R, Fang F. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. N Engl J Med 2017; 377: 699.
  • 35. Devinsky O, Marsh E, Friedman D, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol 2016; 15: 270-278.
  • 36. Aguirre-Velazquez C. Report from a survey of parents regarding the use of cannabidiol (medicinal cannabis) in Mexican children with refractory epilepsy. Neurol Res Int 2017; 2017: 1-5.
  • 37. Epilepsy Society of Australia. Marijuana and medicinal cannabis in the treatment of epilepsy — November 2016. http://www.epilepsy-society.org.au/downloads/MarijuanaandMedicinalCannabisinthetreatmentofepilepsy-November2016.pdf (viewed Dec 2017).
  • 38. Martin JH, Schneider J, Lucas CJ, et al. Exogenous cannabinoid efficacy: merely a pharmacokinetic interaction? Clin Pharmacokinet 2017; (December): 1-7.
  • 39. Gaston TE, Bebin EM, Cutter GR, et al. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia 2017; 58: 1586-1592.
  • 40. 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.
  • 41. Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers 2009; 4: 1770-1804.
  • 42. Wang GS. Pediatric concerns due to expanded cannabis use: unintended consequences of legalization. J Med Toxicol 2016; 13: 99-105.
  • 43. Souza DCD, Ranganathan M, D’Souza D, et al. Medical marijuana: is the cart before the horse? JAMA 2015; 313: 2431-2432.
  • 44. Handwerk B. Modern marijuana is often laced with heavy metals and fungus. Smithsonian.com 2015; 23 Mar. http://www.smithsonianmag.com/science-nature/modern-marijuana-more-potent-often-laced-heavy-metals-and-fungus-180954696/?no-ist (viewed Dec 2017).
  • 45. Therapeutic Goods Administration. Poisons Standard June 2017. https://www.legislation.gov.au/Details/F2017L00605 (viewed Dec 2017).
  • 46. Therapeutic Goods Administration. Access to medicinal cannabis products. 3 October 2017. https://www.tga.gov.au/access-medicinal-cannabis-products (viewed Dec 2017).
  • 47. Royal Australian College of General Practitioners. Medicinal use of cannabis products: position statement — October 2016. http://www.racgp.org.au/download/Documents/Policies/Clinical/RACGP-position-on-medical-cannabis.pdf (viewed Dec 2017).
  • 48. Belackova V, Ritter A, Shanahan M, et al. Medicinal cannabis in Australia – framing the regulatory options. Sydney: Drug Policy Modelling Program, 2015. https://ndarc.med.unsw.edu.au/resource/medicinal-cannabis-australia-framing-regulatory-options (viewed Dec 2106).
  • 49. Office of Drug Control. Importers and manufacturers of medicinal cannabis products. https://www.odc.gov.au/importers-and-manufacturers-medicinal-cannabis-products (viewed Dec 2017).
  • 50. Therapeutic Goods Administration. Medicinal cannabis products - declaration of conformity with Therapeutic Goods Order (TGO) 93. 2017. https://www.tga.gov.au/form/medicinal-cannabis-products (viewed Dec 2017).

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