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"Simple it’s not, I’m afraid you will find, for a mind maker-upper to make up his mind"
— Dr. Seuss

The use of medical marijuana is contentious. Clinical practitioners are caught between a rock and a hard place as the federal government has yet to deem marijuana legal. It is considered a Schedule 1 drug with no accepted medical use and a high potential for abuse while some states have enacted bills authorizing prescribers to provide marijuana based products.1

Organizations such as the American Epilepsy Society (AES)2, Epilepsy Foundation, and the American Academy of Neurology (AAN)3 have issued position statements calling for more research on the use marijuana-based products.

History of Cannabis and Epilepsy

Marijuana is derived from the plant cannabis sativa, which contains more than 60 different pharmacologically active compounds referred to as cannabinoids. The euphoric effects and the potential long-term side effects on cognition and memory are thought to be related to the major psychoactive component Delta-9-tetrahydrocannabinol (THC); however, the other cannabinoid compounds such as cannabinol and cannabidiol (CBD) are thought to have therapeutic benefits in a number of neurologic conditions including epilepsy.

There is historic data dating back to 1800s as well as small number of case studies, anecdotal reports, and laboratory data supporting the use of CBD in the control of seizures. Social media and public pressure have sparked renewed interest in the use of CBD for refractory epilepsy.4 Safety issues and obstacles relevant to cannabis based treatment in epilepsy have recently been highlighted in a New England Journal of Medicine article by Drs. Devinsky and Friedman.5

Anecdotal Reports on Cannabis in the Treatment of Refractory Epilepsy

Medically refractory epilepsy is defined as “a failure of adequate trials of two tolerated, appropriately chosen and used anticonvulsant drug schedules either as monotherapy or in combination to achieve sustained seizure freedom.6 About 30 % of people with such intractable epilepsy may be candidates for curative resective epilepsy surgery or may benefit from alternate therapeutic options such as vagus nerve stimulation (VNS), responsive neurostimulation (RNS), ketogenic diet, modified Atkins diet, or low Glycemic Index diet.7

There has been some favorable data with the use of cannabidiol-enriched cannabis extracts in children with severe, catastrophic, or early onset medically refractory epilepsy such as Lennox-Gastaut syndrome (mixed epilepsy syndrome with developmental disability, LGS) or Dravet syndrome (a severe myoclonic epilepsy of infancy) based on patient and caregiver surveys, with about 80 % reduction in the frequency of seizures.8

The cannabis extracts obtained from various online sources and dispensaries, however, have shown significant fluctuations in their compositions with variable concentrations of CBD and THC from batch to batch. Their reliability thus is terrible.

Ongoing Research into the Use of Cannabis in the Treatment of Epilepsy

In a FDA authorized, expanded access compassionate use program for CBD, a consortium of 10 epilepsy centers has been collecting prospective observational data on children and young adults with severe epilepsy. These patients received Epidiolex, a purified cannabis extract containing 99% cannabidiol and less than 0.10% Δ9-THC (GW Pharmaceuticals).

Among 137 patients with the most common diagnosis of LGS or Dravet syndrome who had received at least 12 weeks of treatment up to a maximum of 25 mg/kg/day, the median reduction in the number of seizures was 54%. Most common adverse events included somnolence, diarrhea, fatigue, decreased appetite, convulsions, and vomiting.

In a recently concluded (March 2016) first phase 3, Epidiolex randomized controlled study in Dravet patients, Epidiolex achieved the primary endpoint of a significant reduction in convulsive seizures compared with placebo over the 14-week treatment period (p=0.01). Other Pediatric epilepsy randomized clinical trials (RCTs) are ongoing in difficult to control epilepsies such as Lennox-Gastaut syndrome and Tuberous Sclerosis Complex.

Filling the Knowledge Gaps

We have significant research gaps for medical marijuana in epilepsy. It is our hope that such carefully conducted trials would close the gap, improve our knowledge, and guide us in the understanding of the efficacy, dosing, side effects, drug-drug interactions, safety, and long term effects of marijuana, especially in growing brain.9

Bibliography

  1. David S. Gloss, MD Edward H. Maa. Medical marijuana-Between a plant and a hard place. Neurol Clin Pract, August 2015 vol. 5 no. 4 281-284.
  2. "Marijuana stops child's severe seizures," CNN, August 7, 2013: http://www.cnn.com/2013/08/07/health/charlotte-child-medical-marijuana/
  3. Daniel Friedman, Orrin Devinsky. Cannabinoids in the Treatment of Epilepsy. N Engl J Med 2015;373:1048-58.
  4. 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(6):1069-1077
  5. Dileep Nair. Management of drug resistant epilepsy. Continuum (Minneap Minn) 2016; 22(1):157–172
  6. 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
  7. Scott E. Hadland, John R. Knight, Sion K. Harris. J Dev Behav Pediatr. 2015 ; 36(2): 115–123.

This content was created through a partnership between the Epilepsy Foundation and American Epilepsy Society.

Authored By: 
Anu Venkat MD
Authored Date: 
09/2016
Reviewed By: 
Joseph I. Sirven MD
on: 
Thursday, September 1, 2016