Epilepsy and other seizure disorders have been at the forefront of the cannabis legalization movement for many years. Marijuana and epilepsy are once again in the limelight, with the recent FDA approval of Epidiolex, a cannabis-derived pharmaceutical. The first of its kind approved in the United States, the pure CBD extract is intended for children with severe epileptic disorders like Lennox-Gastaut and Dravet Syndrome.
The medical benefits of marijuana are gaining more attention as the gradual end of prohibition is making high-quality medical marijuana widely available in more than half the states in the nation. The increased publicity surrounding Epidiolex has left many wondering, "What is the link between marijuana and epilepsy, and why is it so effective treating seizure disorders?"
As the fourth most common brain disorder, epilepsy currently affects about 2.2 million Americans. Nearly, 150,000 people in the United States are diagnosed with the disorder each year. Epilepsy is caused by a wide variety of events, including brain injury or trauma, congenital abnormalities, genetics, infections, brain cancer or tumors, and neurological trauma like stroke or chronic inflammation.
Essentially, epilepsy is a chronic neurological disorder triggered by abnormal activity in the brain which can cause seizures, involuntary movement, paralysis, loss of consciousness, confusion, memory loss, coordination problems, cognitive difficulty, and mood swings.
Seizures, themselves, are not the disease, they are merely an outward expression of an underlying issue in the brain. Consequently, surges of electrical activity cause an imbalance in how the brain functions. The severity of seizures varies; while some may experience seizures which are barely noticeable, other seizures can be completely incapacitating.
What Happens in the Brain During a Seizure?
The brain communicates with the body through excitatory neurotransmitters, like glutamate. Meanwhile, inhibitory neurotransmitters work to control these signals. In the event of a brain injury, infection, inflammation, or another trigger, the delicate balance between these neurotransmitters is skewed and the excitatory transmitters run wild. Over time, the brain becomes more susceptible to seizures and neurons become hyper-excitable.
Unfortunately, this hyperexcitability spreads throughout the neural network in the brain, causing groups of neurons to misfire and seizures spread to other areas of the brain.
Additionally, cytokines, or pro-inflammatory cells, are released during a seizure, as well. By inhibiting glutamate reuptake, the brain experiences an excessive build-up of glutamate. Eventually, this increases damage to the brain and eventually causes brain cells to die.
Traditional Treatment Options
Although there are several pharmaceutical medications available for reducing the frequency and slowing the spread of seizures, for many, the side effects can be troublesome.
Anticonvulsant medications include:
- Diazepam – effective yet short-term anticonvulsant usually used in emergencies.
- Carbamazepine and phenobarbital – most common for partial and generalized seizures.
- Eslicarbazepine and oxcarbazepine – daily medications to help control seizures.
- Phenytoin – an anticonvulsant administered intravenously to control active seizures.
Unfortunately, these medications also come with a long list of side effects including:
- Tiredness and fatigue
- Dizziness and headache
- Sleep disturbances
- Loss of Appetite
- Nausea and vomiting
- Vision changes
Additionally, long-term use can lead to cognitive changes like irritability, increased anxiety, mood swings, aggression, paranoia, bone thinning, hair growth, liver and pancreas damage, blood clotting problems, and kidney problems.
Marijuana and Epilepsy
After the endocannabinoid system was discovered in the early 90s, research raced to understand how this system works to regulate various physiological functions to achieve homeostasis, or balance within the body. Although we are still learning, today we know supplementing the endocannabinoid system with phytocannabinoids from the cannabis plant, like THC and CBD, produces medicinal effects in a wide variety of ailments, including controlling seizures.
The Basics of Cannabinoids
Before diving into marijuana and epilepsy, there are a few basics about cannabinoids to understand. The endocannabinoid system works to control various physiological functions in the human body through a series of receptors within the endocannabinoid system as well as other receptors. The ECS has two receptors that we know of: CB1 receptors, typically abundant in the central and peripheral nervous systems, manage physiological functions involving mood, memory, appetite, and sleep. CB2 receptors, on the other hand, are abundant in the immune system, digestive tract, and other tissues.
Additionally, the body produces two endocannabinoids, anandamide, which primarily binds with CB1 receptors and 2-Arachidonoylglycerol, which binds with both CB1 and CB2 receptors. Phytocannabinoids include tetrahydrocannabinol (THC) which binds with CB1 receptors to produce medicinal effects, as well as the euphoric effects often associated with marijuana.
Cannabidiol (CBD), produces medicinal benefit with no psychoactive effects because it doesn't bind the CB1 receptor in the brain. Rather, this cannabinoid binds with other receptors to produce therapeutic effects. CBD can even counteract the psychoactive effects of THC two ways:
- By binding with the CB1 receptor's allosteric sites, CBD prevents THC from binding with CB1 receptors.
- CBD prevents THC from binding with a group of enzymes in the liver
Anecdotes or Science
In 2013, a young girl named Charlotte Figi suffering from debilitating seizures due to Dravet Syndrome brought the potential of cannabis to mainstream media. Experiencing nearly 300 grand mal seizures a week by the age of five, doctors had all but given up trying to figure out how to help Charlotte. Devastated by the prognosis, Charlotte's parents tried cannabis oil. Within her first doses, the seizures stopped, and by the age of six, her seizures had reduced to just two or three per month and mostly occurred in her sleep.
More recently, 12-year-old Billy Caldwell's illness was thrust into the media spotlight when his mother was caught attempting to bring cannabis oil from Canada into the UK to treat his seizure disorder. Despite being seizure-free for more than 8 months, authorities at Heathrow airport confiscated the cannabis oil and the seizures started again. Fortunately, some of his medicine was eventually returned.
Anecdotal stories of cannabis success like these, tug at the heartstrings, show the possibilities for cannabis and help alleviate any negative connotation associated with consuming this misunderstood plant. However, policymakers and lawmakers require more concrete evidence. Fortunately, the science behind the miraculous results is emerging as more researchers focus on the medical benefits of marijuana.
How Cannabis Actually Helps
As legalization continues to creep across the nation and the world, more science is emerging to support the anecdotal stories about the effectiveness of marijuana for epilepsy. Today, research has shown cannabinoid therapy may help epilepsy and other seizures disorders in several ways:
Increasing Internal Cannabinoids to Reduce Excitotoxicity
The endocannabinoid system helps to control the excitability of neurons in the brain by producing anandamide, a cannabinoid produced internally, to activate CB1 receptors and produce neuroprotective effects. Cannabidiol enhances this process by preventing enzymes from metabolizing anandamide, thus allowing an increased, natural activation of the CB1 receptor.
Reduces Seizure Activity
Tetrahydrocannabinol, or THC, is most infamously known for the psychoactive, cerebral effects is caused by binding with the CB1 receptors. However, by activating this receptor, THC can also control seizure activity by reducing calcium spikes in the brain. Similarly, CBD has been shown to produce antiepileptic effects by controlling calcium levels and inhibiting certain calcium channels which help control excitability and control calcium overload.
Even the US Government admits cannabinoids have neuroprotective abilities with Patent #6630507. Inflammation, over-excited neurons, and excessive calcium buildup in brain cells cause the condition to worsen, increase the production of free radicals and eventually lead to cell death. As a potent neuroprotective/antioxidant and powerful anti-inflammatory, CBD slows down neuron damage.
- CBD suppresses cytokine production to reduce inflammation
- CBD helps to prevent toxic calcium buildup
- Suppresses glutamate transmission to decrease excitotoxicity
- CBD influences other receptors like adenosine receptors and glycine receptors to reduce excitability
Scientific Studies for Medical Marijuana
Last year, a study out of Mexico, showed 17 percent of the participants experienced complete relief from epileptic symptoms, another 53 percent reported a 75 percent reduction in symptoms of Lennox-Gastaut syndrome.
"It is exciting to see such widespread news coverage of these study results by the Mexico media, as studies that prove the therapeutic benefits of CBD [cannabidiol], like Dr. Garza's study, will continue to help fuel less restrictive medical cannabis programs, not only in Mexico but across the globe," Dr. Stuart Titus said in a press release.
"In addition, as news spreads of this revolutionary treatment for diseases, such as epilepsy, more patients, and families that suffer from debilitating medical conditions will receive help with medical marijuana," he added.
Another study, published nearly 40 years ago in 1980, proves the safety of CBD. Researchers provided healthy adults and epilepsy patients with CBD or a placebo. None of the participants reported any adverse effects from the cannabis extract, nearly half (7 of 15) of the patients with epilepsy reported symptom improvement. Astonishingly, four participants reported being 100 percent seizure-free at the end of the study.
A more recent study published in the New England Journal of Medicine showed a 39 percent decrease in seizure frequency in children with Dravet's syndrome, like Charlotte. In fact, multiple human clinical studies have shown cannabinoids’ effectiveness for epilepsy and other seizure disorders:
- A study published in 2013 in the Journal of Epilepsy and Behavior surveyed parents who used CBD-enriched cannabis for their children with a seizure disorder which were unresponsive to traditional treatments and therapies. After treating their children with CBD-enriched cannabis, 16 of 19 parents reported improvement in their children's seizure frequency. Two children were reported being completely seizure-free and another eight saw an 80 percent improvement. The remaining six children experienced 25-60 percent improvement in seizure frequency. Parents even reported significant improvements in other symptoms, including better sleep, alertness when awake, and improved mood.
- Additionally, this study from 1980 involving 16 healthy volunteers and 15 epilepsy patients proved CBD is an effective antiepileptic drug, which can enhance the effects of current medications. Epilepsy patients were divided into two groups. While continuing their traditional medications, eight received CBD and the rest received a placebo for four and a half months. No participant reported adverse reactions, and four epilepsy patients consuming CBD reported being seizure-free, noting a major improvement in their symptoms, while three others reported partial improvement.
- In a clinical trial for Epidiolex, Mayo Clinic took part in a human with children suffering from severe childhood-onset epilepsy who have not responded well to traditional antiepileptic medications. These children took part in a study with their parents and physicians not knowing if their child is receiving Epidiolex or placebo. After 12 weeks, all children were given CBD without the knowledge of their parents or physicians. The study showed children receiving CBD had a 39 percent improvement in seizure frequency, while those receiving a placebo showed a 16 percent improvement. Additionally, researchers noted the children were able to continue their traditional medicines without interference, and the CBD supplement was well tolerated by all participants in the study.
Marijuana and Epilepsy: A Promising Future Together
While so many ailments have eluded modern medicine and traditional pharmaceuticals, this ancient, herbal remedy may prove to be the future of disease treatment and prevention. As more stories emerge showing the true potential of this illustrious plant to treat both young and old, so is the science and research proving the efficacy of cannabinoid therapy to treat epilepsy, seizure disorders, and a broad range of neurological disorders.
The variations and symptoms of epilepsy are as diverse as the range of afflicted individuals. With more than 400 compounds in the marijuana plant, the complex nature of this plant may be well-suited for the complexities of epilepsy as well. Naturally, more research needs to be completed to understand how the myriad of cannabis cannabinoids and terpenes interact with each other to provide the broad spectrum of effects and medical benefit.
Now, with GW Pharmaceuticals clearing the path, and the first cannabis-derived medicine receiving federal approval for the treatment of epileptic conditions, the horizon looks promising for the research and development of other cannabinoid compounds, not only for the use in seizure disorders but in the use of other treatment-resistant conditions, as well.