High-Quality Studies Finally Prove CBD Effectively Treats Epileptic Seizures
by Gaurav Dubey (M.S. Biotechnology) President & Co-founder Karmik, LLC & Clinical Researcher in Pediatric Cardiothoracic Surgery at Rush Medical Center in Chicago, IL.
Modern Medicine, Welcome (Back) Medical Cannabis
The re-integration of Cannabis Sativa into the modern pharmacopeia has brought with it unparalleled insight human physiology and disease. The concomitant discovery of the endocannabinoid system, a powerful physiological control system, has opened up new frontiers in disease research. Childhood epilepsy is one such disease that has increasingly been the target of cannabinoid therapy for years and is the focus of a new documentary by The Medical Cannabis Community that tells the riveting story of a courageous little girl named Emme and her battle with the disease (Perucca, 2017).
CBD Goes Viral
The dramatic anticonvulsant effects of cannabidiol (CBD), a non-psychoactive constituent of the cannabis plant, went viral following a CNN documentary about a little girl named Charlotte and her road to recovery using cannabis. Charlotte had a severe form of childhood epilepsy called Dravet’s syndrome and suffered from around 50 seizures a day until her mother, much like Emme’s mother, painstakingly found an alternative treatment for her daughter that was the most unexpected: cannabis oil that doesn’t get you high (Maa & Figi, 2014). By titrating doses of CBD rich cannabis oil (from a strain now called “Charlotte’s Web”), her mother noticed significant improvements that only got better over time. Ultimately, Charlotte was able to cease all her pharmaceutical drugs altogether and was one of the first of many success stories in using CBD for childhood epilepsy. Similarly, here is the story of Emmerson King.
This is the story of Emme King, a pediatric patient of the Illinois Medical Pilot Program.Her experience will make you question everything you have ever been taught about this plant, and open your mind to all the great life saving possibilities.#EducationAwarenessAccess #EmmeStrong
Posted by The Medical Cannabis Community on Friday, November 2, 2018
Miraculous Anecdotal Evidence Still Isn’t Evidence: The Quest for Proof
While stories like Emme’s and Charlotte’s started growing in number, people witnessed firsthand the most helpless and innocent of society go from hundreds of seizures a week to a handful in a month. Each one was even more compelling than the one before, tugging at heartstrings which made it that much harder to ignore. Nevertheless, the medical community has a high bar for deeming something as true and demanded irrevocable proof that CBD is indeed efficacious in the treatment of epilepsy-induced seizures in pediatric epilepsy patients. Stigmatization, legal hurdles, challenges in sourcing quality product and affordability are barriers to access many parents with epileptic children face today, especially those in the Dravet and Lennox-Gastaut populations. The establishment needed solid proof before making this safe, life-saving treatment more readily available for the public. Indeed, that’s just what they got.
The Facts Are In: A Big Win for Medical Cannabis
While the use of CBD for epilepsy has been a hot topic for quite some time, it is only recently that hard evidence has become available to prove that. High quality, placebo-controlled trials have demonstrably proven CBD’s efficacy in treating epileptic seizures through the attenuation of neuronal excitability and reduces seizure threshold (Do Val-Da Silva et al., 2017) (Perucca, 2017). Charlotte’s story set the stage for many more children, like Emme, to become powerful and courageous pioneers in the medical cannabis movement through their inherent sacrifice.
After years of relentless research, that proof finally exists and may have the power to influence the reclassification of cannabis as a drug (components of which now have federally recognized medical value).
FDA Approves First Ever Cannabis Derived Drug: Epidiolex
Childhood epilepsy and patients that suffer from it have now become the bravest and boldest of pioneers in medical cannabis research and the evolution of the movement. Three tier one, high-quality placebo controlled trials have finally established the therapeutic efficacy of cannabidiol (CBD), a non-psychoactive constituent of the cannabis plant, in treating severe forms of intractable childhood epilepsy (Perucca, 2017). The impact of these findings was so powerful that with it came Epidiolex: a nearly pure formulation of CBD and the first FDA approved pharmaceutical drug containing an active ingredient derived from the cannabis plant (FDA.gov). Put simply, CBD reduces the hyper-excitation and excess firing of neurons in the brain that causes seizures. Digging a little deeper, we find a harmonious variety of potential mechanisms working in the intricate, elaborate ways that cannabinoids work.
Endocannabinoid Signaling & Cannabinoid Therapy in Seizure Regulation
The endocannabinoid system is known to play a part in countless biological functions, including the regulation of synaptic transmission and the rate at which they fire (Perucca, 2017). In our brain, there are neurons responsible for the release of glutamate (excitatory) and GABA (inhibitory), both of which control neuronal excitability. Studies have shown the body’s endogenously produced cannabinoid anandamide is reduced in cerebral spinal fluid in some epileptic patients, indicating an imbalance of the endocannbinoid system is responsible for the dysregulation that causes seizures (Romigi et al., 2010). Alcohol is a well-known depressant that acts by causing disinhibition by activating GABA pathways. CBD acts on CB1 receptors on the pre-synaptic terminal of GABAergic and glutaminergic neurons to mitigate signal release and attenuate neuronal firing (Perucca, 2017). This is how CBD, be it from Epidiolex or concentrated oil from your local dispensary, helps reduce and prevents seizures in epileptic children.
CBD Alters Metabolism of Anti-Epileptic Drugs to Improve Their Efficacy
The placebo-controlled studies in the Dravet and Lennox-Gastaut populations utilize a purified CBD product as “adjunctive therapy”, which showed significant clinical efficacy (Perucca, 2017). The studies make clear that it cannot be concluded that CBD alone reduced seizures or, if in fact, it’s effects on the metabolism of the anti-seizure drugs already being taken by the patient were more responsible. In fact, it is highly likely there is a combination of both underway as CBD has documented CYP450 inhibitory action, which means it affects a very common pathway numerous drugs utilize for their own metabolism and thus, may increase plasma levels of those drugs. However, stories like Emme’s have shown that children are able to cease pharmaceuticals altogether, calling this theory into question and warranting the need for more research.
An MD (Medical Doctor) turned ND (Naturopathic Doctor) Talks CBD Pharmacokinetics
To get a really nerdy perspective on this cytochrome inhibition phenomenon, I reached out to cannabis researcher, Dr. Kareem Kandil (MD/ND):
“CYP inhibition is known in pharmacology to be both an asset or adversity depending on co-management of medications. There is most likely a combined synergy of the anticonvulsant effects of CBD as well as elevation of plasma levels of co-administered anticonvulsant medications. The fact that exclusive placebo controlled trials can attest to the anticonvulsant effects of CBD shows it’s not an “either/or” situation of CBD efficacy being in its inherent anticonvulsant effects vs enhanced pharmacokinetics but most likely both in certain population subsets”
The Importance of Independent Testing & High-Quality Product
The importance behind obtaining lab-tested product from a reliable source cannot be overstated enough. The popularity of CBD oil has created a wave of snake oil salesmen that sell products that sometimes lack CBD entirely or even contain higher levels of the infamous cannabinoid THC instead (Hazekamp, 2018). The fact it can have significant interactions with other drugs due to its metabolic pathway make it all the more necessary to ensure products are tested. Emme got her products from IL dispensaries, which have an extremely high standard and require all products to be tested carefully. Patients taking Epidiolex can be relatively certain of their medication’s purity. However, the explosion of CBD retailers warrants a healthy level of skepticism in the name of safety and quality when approaching an unknown vender. Independent testing of the product by an independent third party is crucial as recent evidence has shown many legal CBD products are not at all what they claim to be
Cannabis’ Schedule 1 Status is More Hypocritical Than Ever Before
The battle against childhood epilepsy and the creation of Epidiolex has set an important precedent in the path to federal recognition of cannabis as a medicine. Unlike Marinol or other synthetic forms of cannabinoids pharmaceutically available, Epidiolex is the first drug that is purely derived from the cannabis plant itself and not synthetic at all. This means an active component of the cannabis plant is an FDA approved medication, thus, making the schedule 1 status of cannabis (stating it has no recognized medical value) the most hypocritical it’s ever been in our nation’s history. Why? Because the “powers that be” currently recognize a component of the cannabis plant (CBD) to have medical value while the whole plant itself (which would likely contain THC) does not.
Easing Cannabis Regulations Allows for More Research and Data
Renewed interest and advocacy of medical cannabis therapy has paved the way for more research and exploration into various diseases that can potentially be treated by cannabis or its active constituents (cannabinoids). Easing the federal restrictions placed on cannabis means more research and development of life-saving treatments; Canada is suggested to set an important precedent in the evolution of cannabis science with legalization being a significant catalyst (Dolgin, 2018). Childhood epilepsy is one such disease that has been the focal point in the medical cannabis movement; countless heartwarming stories of healing in society’s most vulnerable population could no longer be ignored.
The lack of incontrovertible scientific evidence has caused the use of concentrated cannabis oil (sometimes known as RSO or “Rick Simpson Oil” after it’s creator), particularly in children with epilepsy, a controversial and challenging ordeal. That incontrovertible evidence now exists and it states with resounding clarity that cannabidiol, a non-psychoactive component of C. Sativa shows demonstrable benefit in reducing the firing of neurons and the number of seizures children experience every week (Perucca, 2017).
The Amount of Evidence is Rising Dramatically
The number of tear-jerking tales of innocent children experiencing tremendous suffering that had seemingly healed overnight by consuming cannabis oil were rising dramatically. Eventually, so did the number of journal articles reporting on studies and experiments surrounding the use of cannabis for seizures (as seen in the figure below):
A 2018 study reviewed a host of evidence from 6 randomized controlled trials and 30 observational studies and concluded pharmaceutical grade CBD is an efficacious adjuvant to epilepsy medication in reducing epileptic seizures (Stockings et al., 2018).
Emme’s Story Teaches Us to Never Give Up and to Never Give Up Hope
The establishment of CBD as an officially recognized medical treatment for childhood epilepsy by the Western allopathic medical establishment is monumentous. Emme’s story is one of hope, courage and accomplishment, which can be seen in her bright eyes and charismatic disposition every day. It reminds each and every one of us to keep moving forward, because there is still a lot of fight left in us. Children like Emme have finally cracked the ceiling and demonstrated to the bureaucracy that science and facts will always prevail. As we continue to push ahead, we will only unearth more of the truth until the deafening sound of irrefutable evidence can no longer be drowned out by archaic, politically biased policies. As we continue to fight, Emme’s story reminds us to never give up and always push forward.
Do Val-da Silva, Raquel A., Peixoto-Santos, J. E., Kandratavicius, L., De Ross, J. B., Esteves, I., De Martinis, B. S., . . . Leite, J. P. (2017). Protective effects of cannabidiol against seizures and neuronal death in a rat model of mesial temporal lobe epilepsy. Frontiers in Pharmacology, 8 doi:10.3389/fphar.2017.00131
Hazekamp, A. (2018). The trouble with CBD oil. Medical Cannabis and Cannabinoids, 1(1), 65-72. doi:10.1159/000489287
Iffland, K., & Grotenhermen, F. (2017). An update on safety and side effects of cannabidiol: A review of clinical data and relevant animal studies. Cannabis and Cannabinoid Research, 2(1), 139-154. doi:10.1089/can.2016.0034
Maa, E., & Figi, P. (2014). The case for medical marijuana in epilepsy. Epilepsia, 55(6), 783-786. doi:10.1111/epi.12610
Romigi, A., Bari, M., Placidi, F., Marciani, M. G., Malaponti, M., Torelli, F., . . . Maccarrone, M. (2010). Cerebrospinal fluid levels of the endocannabinoid anandamide are reduced in patients with untreated newly diagnosed temporal lobe epilepsy. Epilepsia, 51(5), 768-772. doi:10.1111/j.1528-1167.2009.02334.x
Stockings, E., Zagic, D., Campbell, G., Weier, M., Hall, W. D., Nielsen, S., . . . Degenhardt, L. (2018). Evidence for cannabis and cannabinoids for epilepsy: A systematic review of controlled and observational evidence. Journal of Neurology, Neurosurgery, and Psychiatry, 89(7), 741-753. doi:10.1136/jnnp-2017-317168
Feature Image Credit: https://estrohaze.com/cannabis-cures-epilepsy/