By now, many have heard of using CBD for epilepsy. But is this just another health trend, or is CBD for epilepsy a legitimate medical option? Cannabidiol (CBD) is a cannabinoid found in cannabis plants (hemp and marijuana) that does not produce intoxication like the other well-known cannabinoid THC. As CBD becomes more well-studied, it has demonstrated many benefits in human and animal studies. Currently, Epidiolex is the only type of CBD that is approved and intended to treat epileptic disorders.
While some of the benefits of CBD have yet to be proven effective, it is now well known that CBD can be a very effective anti-seizure compound [3]. Of course, retail CBD products are not the same as a pharmaceutical preparation of CBD that is manufactured and formulated according to proven methods with rigid quality control.
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The History of CBD for Epilepsy
For many years, there was a secretive network of parents of children with intractable epilepsy that would have to go through illegal underground channels to find CBD oil to give their children. Charlotte Figi was one of those children whose story caught headlines and brought the Charlotte's Web hemp strain into the public eye. Pharmaceutical companies like GW Pharmaceuticals took notice and realized that there was a need for a safe and legal product that could provide a reliable option for this community. In 2014, clinical trials began on the pharmaceutical Epidiolex which is a standardized CBD formulation [1].
Patients (n=214) with intractable seizures (at least four weekly) were monitored over a 12-week period (relative to a four-week baseline) with initial CBD doses of 2.5-5 mg/kg/day, increasing weekly to 25 or 50 mg/kg/day. Overall, a 36.5% median reduction of motor seizures was reported (49.8% for Dravet syndrome patients), and five patients were free of all motor seizures (of the patients with motor and atonic seizures, 39% and 56% showed a >50% reduction of seizures, respectively).
Arzimanoglou, A., et al. (2020). Epilepsy and cannabidiol: a guide to treatment.
The trials were a success and Epidiolex was granted FDA approval. This meant that doctors could prescribe this form of CBD for epilepsy to qualifying patients, including young children. However, the cost of Epidiolex has proven to be problematic and has dampened the excitement around the revolutionary drug and left many parents still attempting to self-treat their children (and adults self-treating) with unapproved CBD products that are not intended for their purposes.
GW Pharmaceuticals also makes Sativex (aka Nabiximol) which is 51% THC and 49% CBD, compared to Epidiolex which is >98% pure CBD. Sativex is approved for use in some countries for neuropathic pain, spasticity, overactive bladder, and other symptoms of multiple sclerosis. When you hear about the medical benefits of marijuana, many of those claims are specific to studies of Sativex. However, some people will extrapolate and take liberties to apply claims more broadly.
*To be clear, it is never safe or legal to treat yourself or another with retail CBD for any medical purpose. It is extremely important to seek out assistance programs and follow the direction of licensed healthcare providers.
CBD for Epilepsy Dosage
Many different dosages and formulations of CBD exist. A dosage is how much and how frequently a substance is taken. The formulation is the specific proportion of ingredients and types of ingredients used to create a product. When it comes to Epidiolex (which is not the same as a retail CBD oil dosage or formulation), up to 10-20 mg/kg/day is generally considered to be an adequate dose [1]. CBD oil doses of 25 mg/kg/day and 50 mg/kg/day have also been commonly studied.
In openlabel studies, doses mostly up to 25 mg/kg/day were used, and in the controlled studies, higher doses up to 50 mg/kg/day were used. The studies on Lennox-Gastaut syndrome, however, show that a significant proportion of children respond to doses of as little as 10 mg/kg/day. Therefore a “start slow” and “increase on a case-by-case basis” strategy is recommended. A starting dose of 5 mg/kg/day, divided in two doses, would appear to be adequate.
Arzimanoglou, A., et al. (2020). Epilepsy and cannabidiol: a guide to treatment.
How Does CBD Help Epilepsy?
There is no definitive mechanism that has proven how exactly CBD helps control seizures and symptoms of epilepsy. However, scientist have some well-supported theories. Let's try to break those down.
First, understand that CBD does most of its work on targets that are not endocannabinoid CB1 and CB2 receptors. One of those major targets is an 'ion channel' (communication channel) called the Transient Receptor Potential Vanilloid (TRPV) [3]. There are more than one 'TRPVs,' TRPV1 is involved with modulating seizures and epilepsy. It is especially sensitive to calcium (Ca2+) which is commonly used by the body to send signals and communicate.
Now that you understand TRPV1 is sensitive to calcium and can interact with CBD, let's talk more about how TRPV1 can modulate seizures and epilepsy. Silvestro, et al (2019) explains that when TRPV1 is activated, 'promotes the release of glutamate and the increase in Ca2+, with consequent neuronal excitability.' Overly excited neurons can create abnormal muscle spasms and other abnormal functions. So CBD is thought to initiate a physiological response when combined with TRPV1 that desensitizes these biological mechanisms and brings calcium levels to normal ranges.
This is why it is said that CBD's antiepileptic action is indirect. CBD itself does not change the symptoms, but it influences other channels in the body and encourages them to function normally. In the most broad sense, CBD is thought to promote homeostasis (physiological balance).
In addition to the theory that CBD for epilepsy work via TRPV1 stabilization, there are also theories that it might have a similar action on T-Type Ca2+ ion channels and the serotonin receptor 5-HT (5-hydroxytryptamine). Both of those targets are also thought to have roles in epilepsy and can likewise have their activity or overactivity balanced through the influence of CBD.
What is Epilepsy?
Epilepsy is a type of condition that can be genetic or acquired through injuries like brain injury or stroke. There are many different types of epilepsy with different causes and symptoms. When an injury or genetic mutation disrupts normal brain cell activity seizures occur. These seizures can involve muscle spasms, abnormal behavior, feeling abnormal sensations, and loss of consciousness. Seizures are given different names based on the causes and/or type of symptoms experienced during the seizure. Here are just some types of seizures and epileptic disorders that are out there:
Clonic Seizures: Seizures with repeated rhythmic jerking movements of one side or part of the body or the whole body
Tonic Clonic Seizures: Seizures that are most commonly associated with epilepsy where a person becomes unconscious, their body goes stiff, and they jerk and shake as their muscles spasm. If a person is standing, they will fall backward. These seizures are usually brief and happen without warning.
Atonic Seizures: Seizures that are similar to a Tonic Seizure except for a person's muscles suddenly relax and become floppy and cause them to fall forward if standing. Both atonic and tonic seizures are brief and people usually recover quickly except for injuries that may occur from falling or spasms.
Dravet Syndrome: A rare but severe epileptic disorder characterized by prolonged (over 5 minutes) seizures. Dravet Syndrome is caused by mutations in the SCN1A gene. Dravet affects children and has other implications such as sleep problems, behavior problems, developmental challenges, increased risk of infection, cognitive impairment, and muscle weakness (ataxia). Dravet is not well controlled by conventional epilepsy treatments which is why it is a main target of CBD for epilepsy.
Lennox-Gastaut Syndrome (LGS): LGS is most common among children from ages 2 to 7 years old. It is a type of epilepsy that causes many different types of seizures in addition to developmental delays, learning challenges, and behavioral problems. LGS can be caused by atypical brain development, stroke, major head injury, brain tumors, brain infections like meningitis or encephalitis, reduced oxygen to the brain, or tuberous sclerosis. Like Dravet Syndrom, LGS does not respond well to conventional epilepsy medications and afflicts children. That is why it is another main target of CBD for epilepsy.
Concluding Thoughts on CBD for Epilepsy
Many people are confused because they hear about the medical benefits of CBD and see it for sale online and in stores. However, in order for a CBD product to claim to be effective for any medical purpose, that individual product must go through clinical trials and FDA approval. Simply put, retail CBD products are not intended to treat epilepsy. However, if you are suffering from a seizure disorder, you should give consideration to CBD and speak with your healthcare provider.
Based on controlled trials, Epidiolex appears to be an effective treatment option for patients with Dravet syndrome, Lennox-Gastaut syndrome and TSC and has a relatively good safety profile, although it should be emphasised that, at least from the controlled trials, CBD does not outperform other drugs and will by no means represent a silver bullet for everyone. It does, however, add to the arsenal of available add-on drugs against these severe forms of epilepsy, in some cases offering substantial benefits.
Arzimanoglou, A., et al. (2020). Epilepsy and cannabidiol: a guide to treatment.
You should never try CBD without medical supervision because it can interfere with other medications. It could be a great option if you are struggling to control your seizures, but don't forget that it can still have side effects and dangerous drug interactions even though it is a naturally derived product.
References
- Arzimanoglou, A., Brandl, U., Cross, J. H., Gil‐Nagel, A., Lagae, L., Landmark, C. J., … & other members of The Cannabinoids International Experts Panel. (2020). Epilepsy and cannabidiol: a guide to treatment. Epileptic Disorders, 22(1), 1-14.
- Dickson, K. (2019). Cannabinoid Conundrum: A Study of Anti-Epileptic Efficacy and Drug Policy (Doctoral dissertation, University of Mississippi).
- Silvestro, S., Mammana, S., Cavalli, E., Bramanti, P., & Mazzon, E. (2019). Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials. Molecules (Basel, Switzerland), 24(8), 1459.
- Wong, M., Devinsky, O., Thiele, E., Appleton, R., Patel, A., Harden, C., … & Morrison, G. (2016). A dose ranging safety and pharmacokinetic study of cannabidiol (CBD) in children with Dravet syndrome (GWPCARE1). In American Epilepsy Society Annual Meeting.
