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Journal of Pediatric Neurology 2017; 15(04): 143-150
DOI: 10.1055/s-0037-1598109
Review Article
Georg Thieme Verlag KG Stuttgart · New York

Cannabidiol for the Treatment of Drug-Resistant Epilepsy in Children: Current State of Research

Christopher L. Anderson
1   Department of Biomedical Engineering, University of Florida, Gainesville, Florida, United States
,
Victoria F. Evans
2   Department of Clinical and Health Psychology, University of Florida, Gainesville, Florida, United States
,
Thomas B. DeMarse
3   Department of Neurology, University of North Carolina, Chapel Hill, North Carolina, United States
,
Marcelo Febo
4   Department of Psychiatry, University of Florida, Gainesville, Florida, United States
,
Cynthia R. Johnson
2   Department of Clinical and Health Psychology, University of Florida, Gainesville, Florida, United States
,
Paul R. Carney
3   Department of Neurology, University of North Carolina, Chapel Hill, North Carolina, United States
› Author Affiliations
Further Information

Publication History

28 September 2016

20 December 2016

Publication Date:
23 January 2017 (online)

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Abstract

The reported effectiveness of these home preparations, especially those with high cannabidiol (CBD) concentrations, has garnered the attention of the medical community. In particular cannabis sativa, known for its lack of a psychoactive effect and high CBD content, has become a target of medical research. The shift in public and political interest to medicinal applications of CBD demands renewed research into its efficacy. Pediatric populations in particular stand to benefit significantly from a better understanding of the safety and efficacy of this novel treatment. This review discusses the current state of CBD research and identifies areas that require further investigation as they pertain to pediatric epilepsy populations. It will especially cover those suffering from refractory epilepsies for which other methods of remediation have not sufficed.

Keywords

cannabidiol - refractory epilepsy - drug-resistant seizures - cannabis - epilepsy
 

  • References

  • 1 Friedlander WJ. The rise and fall of bromide therapy in epilepsy. Arch Neurol 2000; 57 (12) 1782-1785
    CrossrefPubMedGoogle Scholar
  • 2 Begley CE, Famulari M, Annegers JF. , et al. The cost of epilepsy in the United States: an estimate from population-based clinical and survey data. Epilepsia 2000; 41 (03) 342-351
    CrossrefPubMedGoogle Scholar
  • 3 Hurst DL. Epidemiology of severe myoclonic epilepsy of infancy. Epilepsia 1990; 31 (04) 397-400
    CrossrefPubMedGoogle Scholar
  • 4 Yakoub M, Dulac O, Jambaqué I, Chiron C, Plouin P. Early diagnosis of severe myoclonic epilepsy in infancy. Brain Dev 1992; 14 (05) 299-303
    CrossrefPubMedGoogle Scholar
  • 5 Trevathan E, Murphy CC, Yeargin-Allsopp M. Prevalence and descriptive epidemiology of Lennox-Gastaut syndrome among Atlanta children. Epilepsia 1997; 38 (12) 1283-1288
    CrossrefPubMedGoogle Scholar
  • 6 Chieffo D, Battaglia D, Lettori D. , et al. Neuropsychological development in children with Dravet syndrome. Epilepsy Res 2011; 95 (01/02) 86-93
    CrossrefPubMedGoogle Scholar
  • 7 Rudgley R. Lost Civilizations of the Stone Age. New York, NY: Free Press; 1998
    Google Scholar
  • 8 Lozano I. The therapeutic use of cannabis sativa L. in Arabic medicine. Journal of Cannabis Therapeutics 2001; 1: 63-70
    CrossrefPubMedGoogle Scholar
  • 9 Warf B. High points: an historical geography of cannabis. Geogr Rev 2014; 104: 414-438
    CrossrefPubMedGoogle Scholar
  • 10 Bennett C, Osburn L, Osburn J. Green Gold in the Tree of Life: Marijuana in Magic and Religion. Frazier Park, CA: Access Unlimited; 1995
    Google Scholar
  • 11 Mechoulam R. The Pharmacohistory of Cannabis sativa. Boca Raton, FL: CRC Press; 1986
    Google Scholar
  • 12 Reynolds JR. Therapeutic uses and toxic effects of cannabis indica. Lancet 1890; 1: 637-638
    PubMedGoogle Scholar
  • 13 Schlosser E. Reefer Madness: Sex, Drugs, and Cheap Labor in the American Black Market. Boston, MA: Houghton Mifflin; 2003
    Google Scholar
  • 14 Cunha JM, Carlini EA, Pereira AE. , et al. Chronic administration of cannabidiol to healthy volunteers and epileptic patients. Pharmacology 1980; 21 (03) 175-185
    CrossrefPubMedGoogle Scholar
  • 15 Department of Health and Human Services. Results from the 2007 National Survey on Drug Use and Health. Washington, DC: Dept. of Health and Human Services; 2008
    Google Scholar
  • 16 Pew Research Center. Majority Now Supports Legalizing Marijuana. Washington, DC: U.S. Politics and Policy; 2013
    Google Scholar
  • 17 Lorenz R. On the application of cannabis in paediatrics and epileptology. Neuroendocrinol Lett 2004; 25 (1–2): 40-44
    PubMedGoogle Scholar
  • 18 Hill AJ, Williams CM, Whalley BJ, Stephens GJ. Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacol Ther 2012; 133 (01) 79-97
    CrossrefPubMedGoogle Scholar
  • 19 Hoeffel J. Medical marijuana gets boost from major doctors group [article]. Los Angeles Times. November 11, 2009
    PubMedGoogle Scholar
  • 20 Borgelt LM, Franson KL, Nussbaum AM, Wang GS. The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy 2013; 33 (02) 195-209
    CrossrefPubMedGoogle Scholar
  • 21 Pertwee RG. The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. Br J Pharmacol 2008; 153 (02) 199-215
    CrossrefPubMedGoogle Scholar
  • 22 Shinjyo N, Di Marzo V. The effect of cannabichromene on adult neural stem/progenitor cells. Neurochem Int 2013; 63 (05) 432-437
    CrossrefPubMedGoogle Scholar
  • 23 Pertwee RG. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol 2006; 147 (Suppl. 01) S163-S171
    PubMedGoogle Scholar
  • 24 Gonsiorek W, Lunn C, Fan X, Narula S, Lundell D, Hipkin RW. Endocannabinoid 2-arachidonyl glycerol is a full agonist through human type 2 cannabinoid receptor: antagonism by anandamide. Mol Pharmacol 2000; 57 (05) 1045-1050
    PubMedGoogle Scholar
  • 25 Kano M, Ohno-Shosaku T, Hashimotodani Y, Uchigashima M, Watanabe M. Endocannabinoid-mediated control of synaptic transmission. Physiol Rev 2009; 89 (01) 309-380
    CrossrefPubMedGoogle Scholar
  • 26 Katona I, Freund TF. Multiple functions of endocannabinoid signaling in the brain. Annu Rev Neurosci 2012; 35: 529-558
    CrossrefPubMedGoogle Scholar
  • 27 Lutz B. On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures. Biochem Pharmacol 2004; 68 (09) 1691-1698
    CrossrefPubMedGoogle Scholar
  • 28 Wallace MJ, Blair RE, Falenski KW, Martin BR, DeLorenzo RJ. The endogenous cannabinoid system regulates seizure frequency and duration in a model of temporal lobe epilepsy. J Pharmacol Exp Ther 2003; 307 (01) 129-137
    CrossrefPubMedGoogle Scholar
  • 29 Jones NA, Hill AJ, Smith I. , et al. Cannabidiol displays antiepileptiform and antiseizure properties in vitro and in vivo. J Pharmacol Exp Ther 2010; 332 (02) 569-577
    CrossrefPubMedGoogle Scholar
  • 30 Geffrey AL, Pollack SF, Bruno PL, Thiele EA. Drug-drug interaction between clobazam and cannabidiol in children with refractory epilepsy. Epilepsia 2015; 56 (08) 1246-1251
    CrossrefPubMedGoogle Scholar
  • 31 Bittigau P, Sifringer M, Ikonomidou C. Antiepileptic drugs and apoptosis in the developing brain. Ann N Y Acad Sci 2003; 993: 103-114 , discussion 123–124
    CrossrefPubMedGoogle Scholar
  • 32 De Petrocellis L, Ligresti A, Moriello AS. , et al. Effects of cannabinoids and cannabinoid-enriched cannabis extracts on TRP channels and endocannabinoid metabolic enzymes. Br J Pharmacol 2011; 163 (07) 1479-1494
    CrossrefPubMedGoogle Scholar
  • 33 Sylantyev S, Jensen TP, Ross RA, Rusakov DA. Cannabinoid- and lysophosphatidylinositol-sensitive receptor GPR55 boosts neurotransmitter release at central synapses. Proc Natl Acad Sci U S A 2013; 110 (13) 5193-5198
    CrossrefPubMedGoogle Scholar
  • 34 Carrier EJ, Auchampach JA, Hillard CJ. Inhibition of an equilibrative nucleoside transporter by cannabidiol: a mechanism of cannabinoid immunosuppression. Proc Natl Acad Sci U S A 2006; 103 (20) 7895-7900
    CrossrefPubMedGoogle Scholar
  • 35 Campos AC, Ferreira FR, Guimarães FS. Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: possible involvement of 5HT1A receptors. J Psychiatr Res 2012; 46 (11) 1501-1510
    CrossrefPubMedGoogle Scholar
  • 36 Hampson AJ, Grimaldi M, Axelrod J, Wink D. Cannabidiol and (-)Δ9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci U S A 1998; 95 (14) 8268-8273
    CrossrefPubMedGoogle Scholar
  • 37 Pack AM. SUDEP: What are the risk factors? Do seizures or antiepileptic drugs contribute to an increased risk?. Epilepsy Curr 2012; 12 (04) 131-132
    CrossrefPubMedGoogle Scholar
  • 38 Young S. Marijuana stops child's severe seizures [article]. Cable News Network. August 7, 2013
    PubMedGoogle Scholar
  • 39 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
    CrossrefPubMedGoogle Scholar
  • 40 Porter BE, Jacobson C. Report of a parent survey of cannabidiol-enriched cannabis use in pediatric treatment-resistant epilepsy. Epilepsy Behav 2013; 29 (03) 574-577
    CrossrefPubMedGoogle Scholar
  • 41 Devinsky O, Sullivan J, Friedman D. , et al. Efficacy and safety of Epidiolex (cannabidiol) in children with treatment-resistant epilepsy: initial data from an expanded access program [abstract]. American Epilepsy Society; 2014
    Google Scholar
  • 42 Hess EJ, Moody KA, Geffrey AL. , et al. Cannabidiol as a new treatment for drug-resistant epilepsy in tuberous sclerosis complex. Epilepsia 2016; 57 (10) 1617-1624
    CrossrefPubMedGoogle Scholar
  • 43 Perry L, Szaflarski J, Bebin E. Investigating the effect of cannabidiol on the EEG. J Neurol 2016; 86: S14.007-S14.007
    PubMedGoogle Scholar
  • 44 Friedman D, Devinsky O. Cannabinoids in the treatment of epilepsy. N Engl J Med 2015; 373 (11) 1048-1058
    CrossrefPubMedGoogle Scholar