For a parent, seeing your child suffer with any type of ailment is enough to create a wrenching heartache and open you up to trying anything to relieve your child’s pain. Such is the case for many parents with children that suffer with seizure disorders beginning with the attempt to determine the root cause of the seizures. A seizure happens when the brain or Central Nervous System (CNS) is overwhelmed by an intense current of electricity coming from a large group of cells that have sent out an electric charge at the same time (WebMD, 2015). Not all seizures end up with the individual on the floor in the thralls of uncontrollable muscle spasms. Some types are barely noticeable; however, these can be just as dangerous in the long run.
Epilepsy is a general description given for a pattern of chronic seizures over an extended period of time (Christopher & Westermeyer, 2014). Epileptic seizures present as three types: Partial seizures, which are confined to a specific part of the cerebral cortex; generalized seizures, which affect both hemispheres of the cerebral cortex at the same time; and unclassified seizures which usually occur in the infant or neonate brain and are specifically difficult to identify due to the immaturity in brain development (Goldenberg, 2010). Epileptic syndromes are diagnosed when the seizures present in specific patterns. They have been identified as: Juvenile myoclonic epilepsy, which begins in adolescence and stems from unknown causes; Lennox-Gastaut syndrome, which is associated with the CNS, presenting when the child is under four years of age; and Mesial temporal lobe syndrome, the most common type of epilepsy, which presents with complex partial seizures and specific diagnostic traits (Goldenberg, 2010).
Though not fully understood, studies have indicated that a malfunction in the synaptic process, either too many excitatory or too few inhibitory neurotransmitters, may be the underlying cause of seizures (Goldenberg, 2010). There are two amino acids, gamma aminobutyric acid (GABA) and glutamate that act as the neurotransmitters transmitting across the synapse. The GABA amino acid is the primary inhibitory neurotransmitter in the CNS and the glutamate is the excitatory neurotransmitter most prominent in the human brain. In order for the synaptic process to be complete, the neurotransmitters must bind, or connect, to one of several corresponding receptors. Receptors are proteins that sit on the membranes of postsynaptic neurons (Sukel, 2011). When excessive neuronal activity happens, endogenous (occurs naturally within the body) arachidonate-based lipid molecules, identified as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), within the endocannabinoid system (ECS) and the endocannabinoid receptors (CB¹ & CB²) are activated (Lutz, 2004). The ECS consists of cannabinoid receptors, endocannabinoid transport system, and metabolic enzymes that break down the ligands (molecules attached to a metal atom) in the body. The CB¹ is expressed in many parts of the brain, including the substantia nigra (dopamine producing), cerebral cortex, hippocampus, cerebellum and amygdala (McPartland, Guy, & DiMarzo, 2014).
The primary treatment for seizure disorders is antiepileptic drug (AED) therapy. There are twenty different pharmaceutical medications approved for AED therapy. The side effects of these drugs include liver toxicity, genetic or developmental abnormalities, and pancreatitis. In addition, there are over 250 warnings, adverse effects, including aggressive, behavioral and psychiatric responses, or other contraindications for this category of Food and Drug Administration (FDA) approved medications (Goldenberg, 2010). The FDA recently approved a study that used a cannabis extract, made with a 50%-50% blend of two primary constituents, cannabidiol (CBD) and delta-9 tetrahydrocannabinol (THC) for the treatment of pediatric epilepsy (Hughes, 2013). The amount of cannabidiol and THC in the cannabis plant varies by species. The Cannabis indica strain is higher in cannabidiol (CBD) where Cannabis sativa is higher in THC. Cannabis indica provides a very relaxing, full-body pain relief while Cannabis sativa is known for a cerebral, uplifting ‘high’. The breeding of Cannabis hybrids seek to bring the best of both species into one plant (Reichard, 2013). Research results indicate that the CBD constituent, processed as oil, reduces seizures with the only adverse effect identified as an increase in appetite (Anderson, 2015). Therefore, the legalization of Cannabis will provide a whole herb alternative for the treatment of childhood seizure disorders eliminating the dangerous side effects that currently accompany pharmaceutical treatments.
Research on this topic was conducted by using the LIRN.net database search, more specifically in the ProQuest; ProQuest Research Companion; eLibrary; Directory of Open Access Journal (DOAJ); Pub Med; Natural Medicines Database; and the Alternative Health Watch. Additional research was conducted in the Library of Anatomy and Physiology; Library of Herbal Medicine; National Center for Complementary and Integrative Health; National Center for Complementary and Alternative Medicine and Google Scholar. The search was conducted for full-text, peer reviewed articles, dated after June 1, 2005, using the following key words and phrases: Childhood Seizure Disorders; Cannabis AND Epilepsy; Endocannabinoid System AND Cannabis; Marijuana AND Seizure Disorders; Cannabis oil; Cannabis oil AND Epilepsy; and Cannabinoid Receptor System.
Extracts of Cannabis have an extensive history of use for neurological disorders. Unfortunately, cannabinoids demonstrate both a pro- and anti-convulsive action. Research into how the ECS works has revealed that endocannabinoids are released at the onset of excessive neuronal action and activates the CB¹ receptors. The idea that the ECS activates on-demand suggests that increasing endocannabinoid levels may lessen seizure frequency by inhibiting cellular uptake and breaking down internal compounds (Lutz, 2004).
After finding a video online, the parents of little Charlotte Figi began their search for a doctor who would approve the use of Cannabis oil for the treatment of their little girl’s seizure disorder. Charlotte was experiencing over 300 seizures a week and the AED therapy wasn’t helping. After an extensive search, the Figi’s found two doctors willing to sign off on the use of medical marijuana for a child as young as Charlotte, only because all other treatment options had been tried and failed. After the oil was administered, Charlotte actually went several hours being seizure free. Giving Charlotte three to four milligrams of oil per pound of body weight, twice a day in her food, stopped the seizures (Young, 2013).
In 2015, Ms. P. Anderson reported on an examination of case reports, qualitative surveys and non-controlled open-label trials, presented at the 68th Annual Meeting of the American Epilepsy Society, which suggested that extracts containing CBD were able to reduce seizures in some patients, especially children. She further reported that the epileptic disorders that appeared to respond best include infantile spasms, Lennox-Gastaut Syndrome (LGS) and Dravet Syndrome (DS). The majority of child participants had not responded to eight different medications, as part of their AED therapy, and had been experiencing seizures for many years. Children with LGS or infantile spasms saw a 92% reduction in seizures and 13% no longer had seizures of any kind. In addition to seizure relief, several children experienced improved sleep, alertness and mood.
Cannabinoids taken into the body, from external sources, can reduce seizures and the degeneration of neurons (Alger, 2014). How this happens is not fully understood, however, there are two theories generally accepted. The first theory involves the synaptic processes that occur in the hippocampus. This sudden electrical charge and resulting excitatory feedback loop inhibits the release of the GABA amino acid and is thought to be the underlying cause of seizures. In studies, mice without CB¹ receptors experienced more deadly seizures leading to the conclusion that cannabinoids provide a protective effect by decreasing the inhibition of the standard inhibitory cells (Gloss & Vickrey, 2013). The second theory explaining the protective effects of cannabinoids involves a single set of glutamate receptors identified as the N-methyl-D-aspartic acid (NMDA) receptors. The use of a synthetic cannabinoid reduced the number of NMDA seizures in mice. With both theories, it is apparent that the acute activation of CB¹ receptors suppresses abnormal excitability reducing seizure activity (Gloss & Vickrey, 2013).
Another rodent study indicated that AEA and 2-AG activate the CB¹ receptors throughout the CNS. The addition of CBD to THC specific species of Cannabis enhances the way CB¹ affects the hippocampus and hypothalamus, acting as an external agonist that will balance the inhibition or excitation of the ECB system without side effects (McPartland, Guy & DiMarzo, 2014).
The twenty medications approved for AED therapy bring with them the potential for over 250 dangerous side effects. In an attempt to identify a pharmaceutical solution, the FDA has granted ‘orphan drug’ designation as a treatment of LGS as well as a ‘Fast-Track’ designation for treatment of DS for the medication, Epidiolex (Epidiolex, 2014). This drug was created by GW Pharmaceuticals in the United Kingdom. The company claims this new drug is ‘pure’ cannabidiol (Hughes, 2013).
The potential for addiction is an excuse given for not using whole plant cannabinoid therapy. Science has shown, however, that it is the THC constituent that carries the potential for addiction, not the CBD constituent most prominent in the Cannabis indica species. When cannabinoids are taken into the body from external sources, like those of Cannabis oil, the ECS is triggered restoring balance and stopping seizures without the side effects of current AED therapy. Children with severe epileptic disorders that have not responded to traditional AED therapy are finding relief from their seizure disorder. The lack of clinical studies utilizing an oil created from the whole Cannabis indica plant have left a dark mark on the qualitative survey studies conducted with the parents of children with seizure disorders.
Conclusions and Recommendations
As has been demonstrated, medications created with ‘standardized’ constituents tend to have side effects because the other constituents that often provide a buffering or synergistic action are left out of the finished product. There was limited information regarding the actual percentage of cannabidiol in the FDA approved medication or whether it was a standardized product. Another positive is the fact that cannabidiol does not have the psychoactive properties that THC does reducing the potential for addiction. Many children have found relief from devastating seizure disorders through the use of Cannabis oil.
Cannabis is either illegal or only legal for medical uses in most states. In the few states where Cannabis has been legalized, parents are often required to find more than one doctor who is willing to recommend the use of the Cannabis oil for children and the limited amount of clinical research makes this even more difficult.
Recommendations presented to ensure the availability of Cannabis oil for children with seizure disorders include:
- Legalization of Cannabis for medical reasons, in all 50 states.
- Continue research on creating whole herb formulas
- Support foundations such as the Realm of Caring Foundation that provide cannabis to adults and children who would not otherwise be able to afford this treatment
- Allow the expansion of Cannabis dispensaries and Cannabis oil producers in all states
- Encourage combined efforts between medical and alternative therapy practitioners as a form of integrated medicine to support research of the ECS and cannabidiol
Alger, B. E. (2014). Seizing an opportunity for the Endocannabinoid System. Retrieved from http://www.medicinalgenomics.com/wp-content/uploads/2011/12/Seizing-an-Opportunity-for-the-endocannabinoid-System.pdf
Anderson, P. (2015). Marijuana Promising in Rare Epilepsies, But It’s Still Early. Retrieved from Medscape website at http://www.medscape.com/viewarticle/837487
Christopher, F. L. & Westermeyer II, R. R. (2014). Seizures in Children. Retrieved from the eMedicineHealth website at http://www.emedicinehealth.com/seizures_in_children/article_em.htm
Epidiolex (2014). Retrieved from the GW Pharmaceuticals website at http://www.gwpharm.com/Epidiolex.aspx
Gloss, D., & Vickrey, B. (2014). Cannabinoids for epilepsy. Cochrane Database System Review, 3. Retrieved from http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD009270.pub3/pdf/standard
Goldenberg, M. M. (2010). Overview of drugs used for epilepsy and seizures: Etiology, diagnosis and treatment. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2912003/
Hughes, S. (2013). FDA approves Cannabis extract study in pediatric epilepsy. Retrieved from Medscape Medical News at http://www.medscape.com/viewarticle/817701
Lutz, B. (2004). On-demand activation of the endocannabinoid system in the control of neuronal excitability and epileptiform seizures. Retrieved from http://www.sciencedirect.com/ science/article/pii/s006295204004769
McPartland, J. M., Guy, G. W., & Di Marzo, V. (2014). Care and feeding of the Endocannabinoid system: A systematic review of potential clinical interventions that upregulate the Endocannabinoid System (ECS). Retrieved from http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0089566
Seizures in Children (2015). Retrieved from the WebMD website, Epilepsy page, at http://www.webmd.com/epilepsy/guide/epilepsy-in-children
Sukel, K. (2011). Brain Receptors – A Primer. Retrieved from The DANA Foundation website at http://www.dana.org/News/Details.aspx?id=43517
Young, S. (2013). Marijuana stops child’s severe seizures. CNN International. Retrieved from http://www.doseofnature.com/wp-content/uploads/2014/10/Marijuana_stops_childs_severe_seizures.pdf