In recent years, there has been a growing interest in the use of cannabis for the treatment of central nervous system disorders such as multiple sclerosis, Parkinson’s disease, and Tourette’s syndrome. One such central nervous system disorder that cannabis can treat is epilepsy, a disease that affects over 45 million people worldwide. Nearly one third of epileptic patients continue to have seizures despite taking the appropriate drug treatments making novel therapies even more important for the health of these patients.
The Endocannabinoid System
In the past 30 years, a growing body of research has clarified the way cannabis interacts with the human body. Cannabis is composed of hundreds of compounds called cannabinoids, a type of molecule. These plant-derived cannabinoids are also known as phytocannabinoids. The most common and widely studied cannabinoids found in cannabis are tetrahydrocannabinol (THC) and cannabidiol (CBD). Unlike THC, CBD does not have any psychotropic effects such as feelings of mild euphoria or intoxication. Researchers in the 1990s discovered that cannabinoids are also present in the human body in the endocannabinoid system (ECS). The ECS plays an incredibly important and complex role in maintaining equilibrium for physiological functions in the body, specifically for the immune system and the central nervous system. Research has found that people with epilepsy have flaws in their endocannabinoid systems—so it’s likely that the ECS plays an important part in the restriction or cessation of seizures and could be an effective therapeutic target.
Two cannabinoid receptors, CB1 and CB2 are present in the ECS. These receptors are part of a class of G protein coupled receptors; CB1 receptors are mostly present in the central nervous system and most CB2 receptors are in the immune system. Animal studies have found that THC is a partial agonist of both of these receptors, meaning it binds to them and activates them, which has an anti-seizure effect. While CBD is not an agonist of CB1 and CB2 receptors it also has been found to halt seizures. The exact way in which CBD reduces seizures is not fully understood, but it may be due to its anti-inflammatory and antioxidant effects in addition to being a positive allosteric modulator of GABAA receptors. As a result, cannabinoids can be thought of as “circuit breakers” as they can stop seizures and the brain cell death associated with epilepsy.
Epilepsy & Cannabis
Since the 1970s there have been numerous observational studies, surveys, and more recently, randomized clinical trials, conducted on the use of medical cannabis for epilepsy. Most of the latest studies are conducted only on CBD due to its lack of psychotropic effects.
Many research studies have had mixed results regarding the effectiveness of CBD for the treatment of epilepsy. Several surveys with adult epileptics and parents of children with epilepsy reported that CBD use reduced seizures by up to 50% while others found no reduction. A few case reports found that CBD improved seizures in some patients while others reported an increase in seizure severity. Four studies done in the past five years found mostly positive results associated with CBD use. One open label trial of a combined THC and CBD medication for children with Dravet syndrome, a form of childhood-onset epilepsy that is particularly challenging to control effectively with available drug therapies, found that participants had a reduction in seizures and improved quality of life. However, none of these studies were double-blind, placebo-controlled and thus their results must be interpreted with caution.
Recently three randomized clinical trials, the gold standard in medical research, assessed the effect of an oral solution of CBD called Epidiolex on seizure reduction.
- A 2017 study tested CBD as a treatment for patients with Dravet syndrome. This study with 120 participants aged 2 to 18 found that those who received a 20 milligram (mg) per kilogram of body weight dose of CBD in addition to their standard drug regimen had a median reduction of monthly seizures of 39% versus 13% in the placebo group.
- In 2018, a double-blind, placebo-controlled trial was conducted at 30 clinical centers with 225 patients with Lennox-Gastaut syndrome, a severe form of childhood onset epilepsy. This study was conducted with patients aged 2 to 55 and added CBD to patients’ drug therapies found that during the treatment period, those who received the 20mg dose of CBD had a median reduction in seizure frequency of nearly 42%, patients who received the 10mg dose of CBD had a seizure reduction of 37% and those in the placebo group had a reduction of 17%.
- In 2018, a randomized, double-blind, placebo-controlled trial at 24 clinical sites in the Netherlands, United States, and Poland was conducted with 171 patients aged 2 to 55 with Lennox-Gastaut syndrome. Participants who received a 20 mg per kilogram of body weight dose of CBD in addition to their standard drug regimen had a median reduction of monthly seizures of 44% compared to 22% in the placebo group.
In addition, these studies found that CBD treatment not only significantly improved seizure control but also had an impact on quality of life. Many patients saw improvements in their mood, sleep, cognitive skills, and had increased appetite.9 Based on the results of these clinical trials, in 2018 the US Food and Drug Administration (FDA) approved the CBD based drug, Epidiolex, to treat those aged two and older for epilepsy caused by Lennox-Gastaut or Dravet syndrome. This is the first ever cannabis derived medication to be approved by the FDA.
Cannabis is believed to be a safe drug treatment—no study on cannabis has reported a death. The majority of reported side effects were mild to moderate, and include fatigue, drowsiness, diarrhea, vomiting, decreased appetite, and fever. CBD does have a drug interaction with clobazam, common epilepsy medication. CBD inhibits the metabolism of this drug often leading to an increase in fatigue and drowsiness in patients. Very rarely patients experienced abnormalities in liver enzymes and this was more common for those who took the epilepsy medication valporate. Further research is necessary to explore the potential interaction between other epilepsy medications and specific doses and forms of CBD as well as any potential long term side effects of the drug. The short side effects of THC can include memory, motor and judgment impairment and the long term effects can include cognitive impairment, a small risk of addiction, and an increased risk of developing a psychotic disorder.
There is large variation between countries in the currently accepted use of medical cannabis to treat epilepsy. Countries such as Australia, Canada, and Croatia explicitly accept medical cannabis as a treatment for epilepsy.
Other nations such as Israel, the Netherlands and Germany allow doctors to prescribe medical cannabis for any condition if standard treatment is not effective for their patient.
In the United Kingdom, it can only be prescribed for epilepsy patients with Lennox-Gastaut and Dravet syndrome.
In the United States, there is state by state variation in the legal status of medical cannabis for epilepsy treatment. Three states (Idaho, Nebraska, and South Dakota) do not allow the use of any form of medical cannabis.
Fourteen states (Alabama, Georgia, Indiana, Iowa, Kansas, Kentucky, Mississippi, North Carolina, South Carolina, Tennessee, Texas, Virginia, Wisconsin, and Wyoming) allow CBD for treatment.
The District of Columbia and 33 states (Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Hawaii, Illinois, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Missouri, Montana, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, Washington, West Virginia, Utah, and Vermont) allow the use of medical cannabis for epilepsy treatment.
Current findings on medical cannabis for epilepsy are promising. Additional high-quality randomized control trials of CBD and THC for the treatment of other, less severe forms of epilepsy are necessary. However, given the existing evidence of the therapeutic benefits of cannabis and the growing levels of interest and investment in cannabis research, it seems likely that more nations will begin to allow patients to access medical cannabis to treat intractable epilepsy. Overall, cannabis is a safe medication with relatively mild risks that has the potential to significantly reduce seizure frequency and improve the quality of life in epileptic patients.
Epilepsy is a group of neurological disorders characterized by seizures, known as epileptic seizures. The seizures are caused by abnormal brain activity and might come along with periods of unusual behavior and sometimes loss of awareness.
However, the hallmark of epilepsy is recurrent and unprovoked seizures that can vary from brief and nearly undetectable periods to long periods of vigorous shaking. Episodes of seizures might result in falling, and subsequently – physical injury. A person is diagnosed with epilepsy after two unprovoked seizures, or one unprovoked seizure with the likelihood of more, that were not caused by other medical conditions like extremely low blood sugar or poisoning.
Experts divide epilepsy into three categories:
Generalized epilepsy – in this condition seizures start on both sides of the brain (or quickly affect networks of brain cells on both sides). The kinds of seizures are:
- Generalized motor seizures – these cause the body to move uncontrollably and are known as clonic seizures or tonic-clonic seizures.
- Generalized non-motor seizures – the seizures are named “absence” seizures because it often seems the person having them is not really there. He/ she might be caught, for instance, staring into space instead of doing something important. This is more common in children
Focal epilepsy – in this condition, seizures develop in a particular area on one side of the brain. That’s why they are called “partial seizures.” Focal epilepsy seizures come in four categories:
- Simple Partial Seizures – In this type of seizure, the person experiencing them is fully aware of what is going on. Usually only one side of the body may be moving and it might be subtle, such as twitching, one hand moving, or one leg twitching.
- Complex Partial Seizures – The person experiencing them has some change in their mental status (but not completely unconscious), so they may only be partially aware of their surroundings or whether they have a seizure. These types of seizures can also present as a change in emotion or mood such as a sudden onset of fear. If the seizure causes motor movements, again it will most likely be one side of the body moving uncontrollably.
- Generalized and focal epilepsy – this category combines both generalized and focal seizures. Some patients may have seizures start with just one side of the body where they do not lose consciousness but eventually they go into a generalized seizure.
Epilepsy is considered a common neurological disorder. It affects 65 million people around the world, of which about three million people live in the US. That makes it about 1% of the population who live with seizures in the USA. In addition, about 1 in 10 individuals will experience a seizure in their lifetime. Nevertheless, nearly 80 percent of cases occur in the developing world. In 2015, there were 125,000 deaths attributed to seizures.
Anyone can develop epilepsy, but it is more common among young children and older adults. It also occurs slightly more often in men than in women.
Epilepsy is characterized by seizures which recur over a long time. These seizures may present in several ways, depending on the part of the brain involved and the person’s age. However, the most common type (60 percent) of seizures are generalized convulsive seizures, meaning they affect the entire body.
All generalized seizures involve loss of consciousness and often happen with forewarning. They almost always last less than a minute. If they last longer than several minutes, they can be dangerous and potentially fatal. Overall, there are six main types of generalized seizures:
Tonic – these involve sudden stiffening and contraction of the muscles. If you are standing while having them, you might fall to the ground
Clonic – usually follow a tonic seizure and involve rhythmic twitching or jerking of one or several muscles
Tonic-clonic – these produce constant contraction of the muscles. They are most noticeable when the limbs contract, followed by their extension along with the arching of the back. After the seizure, there is often a “postictal state,” in which the shaking stops and it takes the person a period of time to return to normal.
Myoclonic – these involve spasms of the muscles in either few areas or all over the body..
Absence – these are barely noticeable since they mostly include only a slight turn of the head or blinking or staring into space. They are called “absence” because while having them, the person is not responsive, albeit for several seconds. It is often misdiagnosed as a child “spacing out.”
Atonic seizures – these involve the loss of muscle activity, typically on both sides of the body, for more than one second.
Epilepsy occurs more often with certain disorders, depending partly on the epilepsy syndrome present. Children with epilepsy, for example, are three to five times more likely to develop hyperactivity disorder. Furthermore, epilepsy is more common in children with autism.
As a neurological disorder, epilepsy is caused by abnormal activity in the brain. When the electric signals coming from the brain become scrambled or create sudden bursts of electrical activity, a seizure occurs.
Epilepsy can have both genetic and acquired causes. In many cases, it is an interaction of both. Younger people are more likely to have epilepsy due to genetic or developmental conditions, while older people are more likely to have them in correlation with strokes and brain tumors. However, in about 60 percent of cases, the cause is unknown. Known causes include:
Researchers have linked some types of epilepsy to specific genes, but genes don’t normally cause epilepsy. Nevertheless, certain genes may increase sensitivity to environmental conditions that trigger seizures.
Epilepsy also sometimes runs in families. Still, the risk of inheriting the condition is considered low (2 to 5 percent). In general, one out of a hundred epileptic people develops the condition by the age of 20.
The risk is still low even if the parent develops epilepsy due to another condition, like a stroke or a brain injury. Seizures due to other inherited conditions like tuberous sclerosis and neurofibromatosis are more likely.
Epilepsy is often a result of other conditions that cause damage to the brain. Stroke is a leading cause of epilepsy in adults over the age of 35 in the USA. Other common causes are brain tumors and developmental disorders like autism. Worldwide, the most common cause of epilepsy is actually an infectious parasite called neurocysticercosis.
The condition can also be caused by injuries including head trauma caused by a car accident or other traumatic injury, as well as prenatal injuries caused before or after birth. Oxygen deficiencies, for instance, can end in epilepsy or cerebral palsy. Another known cause is infectious diseases, such as meningitis, AIDS, and viral encephalitis.
These do not cause epilepsy but rather increase the chance of having it or worsen the symptoms. Mainly, epileptic seizures might be triggered due to:
- Age – epilepsy can occur at any age, but the onset is most common in children and older adults.
- Seizures in infancy – High fevers in childhood can sometimes be associated with seizures.
- Psychological conditions – If someone suffering from epilepsy has many stressors that lead to decreased sleep that could decrease their seizure threshold and increase their chance of having a seizure.
- Exposure to light – frequent bright or flashing light, whether when driving or watching movies, can trigger seizures.
- Drugs – caffeine, alcohol and certain medications affect the brain in a way that might trigger seizures.
The diagnosis process begins by reviewing your symptoms and medical history. Your doctor may order several tests to see if epilepsy is causing the seizures or other similar conditions. The tests are likely to include:
- A neurological exam – this will test your behavior and mental function to determine the type of epilepsy you may have.
- Blood tests – a blood sample to seek for signs of infections, genetic conditions or other possible causes associated with seizures.
- Electroencephalogram (EEG) – this is the most common test used in diagnosing epilepsy. It is conducted by attaching electrodes to your scalp with a paste. In some cases, it is performed while you’re asleep. The electrodes are then used to record the electrical activity of your brain.
- Imaging tests – included in these tests are CT scans, MRIs, positron emission tomography (PETs), as well as a single-photon emission computerized tomography. The MRI is considered to be the gold standard for brain scans, including diagnosing epilepsy, and they can additionally reveal tumors and other abnormalities in the brain otherwise unnoticed.
The mainstay of epilepsy treatment is medications that reduce your chances of having a seizure. There are also other forms of treatment including nerve stimulation and for patients who are eligible and have refractory symptoms, sometimes surgery is an option.
Many people with epilepsy can attain seizure freedom by taking one anti-seizure medication, also known as anti-epileptic medication, or anticonvulsant. For others, it only decreases the frequency of seizures they experience. Many children with epilepsy can eventually stop taking medication and live a life with no more seizures.
The prescribed medication depends on your condition, frequency of seizures, your age, and other factors. Your doctor also needs to make sure the anti-epileptic medications don’t interact with other drugs that you are taking. Anti-seizure medications may have adverse effects, such as fatigue, dizziness, speech problems, and problems with memory. Rare and more severe side effects include depression, severe rash, and inflammation of certain organs, such as the liver.
When medications fail to control the seizures, surgery may help. In such surgery, the area of the brain that’s causing the seizures is removed.
Doctors usually perform surgery when tests show that the seizures originate in a very small and specific area in the brain which doesn’t interfere with vital functions like language, vision or hearing. However, even after successful surgery, many people need to continue taking medication. Surgery clearly carries its own risks with potential complications and adverse effects.
These therapies are considered as an alternative to the previous two options.
- Vagus nerve stimulation – Doctors implant a “vagus nerve stimulator” device inside the chest. This device sends electrical bursts through the vagus nerve, directly to the brain; it has a mild success rate, 20 – 40%, in reducing the frequency of the seizures.
- Ketogenic diet – This strict diet is high in fats and low in carbohydrates. It is reported that some children managed to reduce their frequency of seizures by following it, and even become seizure-free a few years later. Uncommon side effects include dehydration, constipation, and kidney stones, as a result of a buildup of uric acid in the blood. If you’re looking for a less restrictive diet, you could also consider a glycemic index and modified Atkins diets.
- Deep brain stimulation – In this procedure, electrodes are implanted into a specific part of the brain, normally the thalamus. They are connected to an implemented generator in the chest or skull which sends electric pulses to the brain to reduce seizures.
Understanding your condition can help you take better control of it. Take your medications regularly and get enough sleep to avoid the sensitivity that triggers seizures. Also, consider wearing a medical bracelet to help emergency personnel reach you on time and know how to treat you correctly. If you witness someone having an active tonic-clonic seizure, roll the person onto their side. This should help in preventing fluids from getting into the lungs and causing life-threatening suffocation.
A seizure is considered a medical emergency if it lasts more than five minutes or the person experiences more than two seizures in one hour, with no recovery in between.
At certain times, epileptic seizures might lead to circumstances that are dangerous to yourself and others. For instance, falling – a common risk for epileptic people – can end in severe injuries and even death. Seizures might also be fatal if you swim alone (which means that you could drown) or if you drive (which could lead to a car accident). That’s why many states restrict the driver’s license of epileptic people according to their ability to control seizures. Avoid being in physical situations where having a seizure can be dangerous. For example, swimming alone, scuba diving, and sky diving are prohibited in those suffering from seizures.
Another major risk for epileptic people is pregnancy complications. Seizures during pregnancy may pose dangers to both mother and fetus. If you are an epileptic woman who plans to have a baby, consult your doctor regarding how to manage your condition before and during pregnancy.