Historically referred to as “Falling sickness”, the word epilepsy itself has a Greek etymology originating from the idea that people in convulsions were being taken hold of (“seized”) by the gods. [1] Epilepsy is so prevalent in our society that even the famous Julius Caesar was thought to have had it. [2] During the month of February, the second Monday of which is International Epilepsy Day, we would like to call attention to the nothing-short-of miraculous success that cannabidiol, or CBD, has had in the treatment of medication-resistant pediatric epilepsy.

Epilepsy is a disease of the Central Nervous System (CNS) characterized by seizures, which can generally be thought of as periods of abnormal, synchronous excitation of an interconnected region of neurons. [3] A person is diagnosed with having epilepsy, or being epileptic, when they experience “recurrent, non-provoked seizures.” [4] A succinct clinical definition endorsed by the International League Against Epilepsy is given below. [5]

 

Cannabis has been a part of human pharmacopoeia for as long as it’s been in recreational use. [6,7] It was introduced to the West during the Victorian era by renown English physician Dr. William Blair O’Shaughnessy. [8] His is the first recorded use in the medical literature of successfully treating epilepsy with cannabis. He is recorded as treating a six-week old baby suffering from convulsions with ethanoic extracts of Cannabis indica, [8] leading him to endorse cannabis as an “anti-convulsive remedy of the greatest value” [9].

Spurred on by mounting anecdotal evidence in the modern era, significant clinical and translational research has been mounted to definitively establish the potential uses of cannabis in the treatment of epilepsy. [10,11] This biomedical research has identified the phytocannabinoids class as the molecules which exert the therapeutic efficacy of cannabis treatments. [12] Cannabidiol, the primary non-psychoactive ingredient in C. sativa, was found to be the largest mediator of this effect. [13] Furthermore, clinical studies have endorsed the safety of CBD in combination with currently available anti-seizure medications. [14]

Certain forms of refractory, medication-resistant epilepsy, such as Dravet and Lennox-Gastaut syndromes, seem particularly targetable by cannabidiol preparations. [15] They are among the most difficult types of epilepsy to control, with nearly all patients continuing to have seizures despite currently available medications, according to the FDA. The large number of seizures puts children at high risk for intellectual and developmental disabilities, as well as death. Because the conditions are so rare, GW Pharmaceuticals received an orphan drug designation for developing Epidiolex, a CBD isolate from C. sativa L. [16]

Figure 1. Bottled solution of Epidiolex, the first FDA-approved medical use of CBD since the classification of cannabis as a Schedule I drug.

 

Isolates of cannabidiol have become the de facto norm for the treatment of these syndromes in the United States (Figure 1). [17] This is in large part due to the complex federal status of the cannabis plant. [18] However, they are not necessarily the most effective cannabis treatments regiment available. [19] For reasons detailed by Mechoulam and Ben-Shabat, cannabinoids show a greater efficacy when administered in unison, a condition termed the “entourage effect.” [20] Administering CBD on its own also presents clinicians with unique dose-response challenges. [21] Therefore, extracts of cannabidiol-rich, THC-poor cannabis strains should be explored as an alternative federally-approved therapy for these conditions.

 

  1. com, search term: “Epilepsy”. Word Origin and History for Epilepsy. Online Etymology Dictionary, © 2010 Douglas Harper. Accessed 2019 Feb 11.
  2. Hughes, JR. “Dictator Perpetuus: Julius Caesar–did he have seizures? If so, what was the etiology?” Epilepsy Behav. 2004; 5(5): 756-64.
  3. Scharfman, Helen E. “The Neurobiology of Epilepsy”. Curr Neurol Neurosci Rep. 2007; 7(4): 348–354.
  4. Stafstrom, Carl E., and Carmant, Lionel. “Seizures and Epilepsy: An Overview for Neuroscientists”. Cold Spring Harb Perspect Med. 2015; 5(6). pii: a022426.
  5. Fisher, Robert S., et al. “A practical clinical definition of epilepsy”, ILAE Official Report. Epilepsia. 2014; 55(4): 475–482.
  6. Reynolds, J.R. “Therapeutical uses and toxic effects of Cannabis indica”. Lancet. 1890; 1: 637-8.
  7. Russo, Ethan B. “History of cannabis and its preparations in saga, science, and sobriquet”. Chem Biodivers. 2007; 4(8): 1614–48.
  8. O’Shaughnessy, W.B. “On the preparations of the Indian hemp, or Gunjah, (Cannabis Indica)”. Prov Med J Retrosp Med Sci. 1843; 5(123): 1–7.
  9. The Dublin Journal of Medical Science (1836-1845)., Volumes 23-24. Link.
  10. Friedman, Daniel, and Devinsky, Orrin. “Cannabinoids in the Treatment of Epilepsy”. N Engl J Med. 2015; 373: 1048-1058.
  11. Szaflarski, J.P., and Bebin, E.M. “Cannabis, cannabidiol, and epilepsy–from receptors to clinical response”. Epilepsy Behav. 2014; 41: 277-82.
  12. Hill, Andrew J., et al. “Phytocannabinoids as novel therapeutic agents in CNS disorders”. Pharmacol Ther. 2012; 133(1): 79-97.
  13. Devinsky, Orrin, et al. “Cannabidiol: Pharmacology and Potential Therapeutic Role in Epilepsy and Other Neuropsychiatric Disorders”. Epilepsia. 2014; 55(6): 791-802.
  14. Geffrey, Alexandra L., et al. “Drug–drug interaction between clobazam and cannabidiol in children with refractory epilepsy”. Epilepsia. 2015; 56(8): 1246-51.
  15. Hussain, Shaun A., et al. “Perceived efficacy of cannabidiol-enriched cannabis extracts for treatment of pediatric epilepsy: A potential role for infantile spasms and Lennox–Gastaut syndrome”.
  16. Kaplan, Sheila. “F.D.A. Panel Recommends Approval of Cannabis-Based Drug for Epilepsy”. New York Times. April 19 2018. Accessed May 22, 2018.
  17. Devinsky, Orrin, et al. “Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial”. Lancet Neurol. 2016; 15(3): 270-8.
  18. Mead, Alice. “The legal status of cannabis (marijuana) and cannabidiol (CBD) under U.S. law”. Epilepsy & Behavior. 2017; 70: 288–29.
  19. Blasco-Benito, S., et al “Appraising the “entourage effect”: Antitumor action of a pure cannabinoid versus a botanical drug preparation in preclinical models of breast cancer”. Biochem Pharmacol. 2018; 157: 285-293
  20. Ben-Shabat, et al. “An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity”. Eur J Pharmacol. 1998; 353(1): 23-31.
  21. Gallily, Ruth, et al. “Overcoming the Bell‐Shaped Dose‐Response of Cannabidiol by Using Cannabis Extract Enriched in Cannabidiol”. Pharmacology & Pharmacy. 2015; 6: 75‐85

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