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
› Institutsangaben
Weitere Informationen

Publikationsverlauf

28. September 2016

20. Dezember 2016

Publikationsdatum:
23. Januar 2017 (online)

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.

 
  • References

  • 1 Friedlander WJ. The rise and fall of bromide therapy in epilepsy. Arch Neurol 2000; 57 (12) 1782-1785
  • 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
  • 3 Hurst DL. Epidemiology of severe myoclonic epilepsy of infancy. Epilepsia 1990; 31 (04) 397-400
  • 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
  • 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
  • 6 Chieffo D, Battaglia D, Lettori D. , et al. Neuropsychological development in children with Dravet syndrome. Epilepsy Res 2011; 95 (01/02) 86-93
  • 7 Rudgley R. Lost Civilizations of the Stone Age. New York, NY: Free Press; 1998
  • 8 Lozano I. The therapeutic use of cannabis sativa L. in Arabic medicine. Journal of Cannabis Therapeutics 2001; 1: 63-70
  • 9 Warf B. High points: an historical geography of cannabis. Geogr Rev 2014; 104: 414-438
  • 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
  • 11 Mechoulam R. The Pharmacohistory of Cannabis sativa. Boca Raton, FL: CRC Press; 1986
  • 12 Reynolds JR. Therapeutic uses and toxic effects of cannabis indica. Lancet 1890; 1: 637-638
  • 13 Schlosser E. Reefer Madness: Sex, Drugs, and Cheap Labor in the American Black Market. Boston, MA: Houghton Mifflin; 2003
  • 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
  • 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
  • 16 Pew Research Center. Majority Now Supports Legalizing Marijuana. Washington, DC: U.S. Politics and Policy; 2013
  • 17 Lorenz R. On the application of cannabis in paediatrics and epileptology. Neuroendocrinol Lett 2004; 25 (1–2): 40-44
  • 18 Hill AJ, Williams CM, Whalley BJ, Stephens GJ. Phytocannabinoids as novel therapeutic agents in CNS disorders. Pharmacol Ther 2012; 133 (01) 79-97
  • 19 Hoeffel J. Medical marijuana gets boost from major doctors group [article]. Los Angeles Times. November 11, 2009
  • 20 Borgelt LM, Franson KL, Nussbaum AM, Wang GS. The pharmacologic and clinical effects of medical cannabis. Pharmacotherapy 2013; 33 (02) 195-209
  • 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
  • 22 Shinjyo N, Di Marzo V. The effect of cannabichromene on adult neural stem/progenitor cells. Neurochem Int 2013; 63 (05) 432-437
  • 23 Pertwee RG. Cannabinoid pharmacology: the first 66 years. Br J Pharmacol 2006; 147 (Suppl. 01) S163-S171
  • 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
  • 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
  • 26 Katona I, Freund TF. Multiple functions of endocannabinoid signaling in the brain. Annu Rev Neurosci 2012; 35: 529-558
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 38 Young S. Marijuana stops child's severe seizures [article]. Cable News Network. August 7, 2013
  • 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
  • 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
  • 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
  • 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
  • 43 Perry L, Szaflarski J, Bebin E. Investigating the effect of cannabidiol on the EEG. J Neurol 2016; 86: S14.007-S14.007
  • 44 Friedman D, Devinsky O. Cannabinoids in the treatment of epilepsy. N Engl J Med 2015; 373 (11) 1048-1058