Cannabidiol (CBD) 

Cannabidiol, commonly known by its abbreviation CBD, is a major component of the Cannabis sativa plant, also better known as cannabis, weed, or marijuana. Unlike the other major component of cannabis, tetrahydrocannabinol or THC, CBD is non-psychoactive, meaning it does not cause the symptoms of mood alteration and changes in perception and consciousness seen when smoking plain cannabis or weed. CBD is also non-addictive and has a completely different mechanism of action within the body as compared to THC.¹

CBD was first isolated from the cannabis plant in 1940, but at the time, it did not harbour much popularity for clinical research, unlike its counterpart THC. However, individual reports of the use of CBD preparations for the treatment of epilepsy, as well as increasing interest in the medical use of cannabis, sparked investigation of CBD in many different conditions.² This article will focus on the use of CBD as a complementary treatment for epilepsy; however, you can learn more about the other possible medical uses of CBD through this link.

Medical use of CBD

The medical use of cannabis in general can be traced back millennia and likely had its origins in China.² Since it has been in the public eye not only due to its possible medical properties but also due to its addictive ones and its recreational use. 

CBD is non-psychoactive, non-addictive, and generally better tolerated. Scientists hypothesise CBD to be useful in a myriad of conditions, including insomnia, anxiety, epilepsy, and psychosis.  However, the medical use of CBD needs further study in many cases. Its claimed benefits are still under research or lack any sort of scientific evidence, and some are only supported by individual accounts, which are not representative of the general population and could be fake.³ Thus, this article will aim to provide the most current evidence for the use of CBD for epilepsy in a scientific and unbiased manner.

Epilepsy

Epilepsy is a condition which affects the brain. It can affect people of all ages and has around 50 million cases worldwide, according to the World Health Organisation.⁴ The condition is characterised by seizures. Seizures are uncontrolled bursts of electrical activity in the brain, which can cause a wide array of symptoms, including:⁵

• Sudden jerking and shaking movements known as fits
• Loss of consciousness or awareness
• Stiffness
• Falls
• Strange sensations (tastes, smells, tingling)

Oftentimes, epilepsy is a chronic illness; however, it can sometimes slowly get better over time. With medication, some epilepsy patients achieve complete remission, that is, a lack of symptoms. However, proper diagnosis and treatment of the condition can be lacking, especially in lower-income countries and due to the stigma and discrimination.⁴

Within the broad description of epilepsy, there also exist different syndromes which are differentiated by the type and nature of seizures being experienced as well as the onset and progression of the condition.⁶ For example, Lennox-Gastaut syndrome is a severe form of epilepsy syndrome with onset in early childhood, with specific common seizure types. Seizure types can be classified by their point of origin in the brain (e.g., focal if starting at a specific point in the brain and then spreading) as well as the movement/symptoms observed during (e.g. tonic describes stiffness in the muscles, while atonic describes muscles being losing strength).^7,8

Current treatments for epilepsy include drugs (anti-epileptic drugs), surgery (removal of parts of the brain causing seizures), vagus nerve stimulation, and a dietary regimen (ketogenic diet).⁵ However, while many patients with epilepsy may respond positively to one or a combination of these, there is a third of the population that will be treatment-resistant, for which alternative therapy methods are being researched.⁹ One of these alternatives is CBD (if you want to learn more about epilepsy, follow this link).

Use of CBD for epilepsy

Currently, CBD has been legalised by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of Lennox-Gastaut and Dravet syndrome in those 2 years of age or older. CBD is mostly given as an adjunct; that is, it is given as an addition to standard medication.¹⁰ 

Evidence

The first interest in CBD use for epilepsy was due to individual accounts of parents reporting CBD preparations had significantly reduced the seizure incidence in their children with epilepsy. This was further supported by online questionnaires, which also noted improvements in mood, sleep, and cognition. Other open-label studies showed similar results, which led to increased interest in the compound and the development of randomised controlled trials, or RCTs.⁹

RCTs are often the most reliable source of information about the effects of a drug. Unlike open-label trials, neither the scientists nor the participants know who is given the treatment and who is given the placebo (non-active treatment). As such, bias is unlikely, and the results are more reliable.¹¹ 

Following individual accounts, a few RCTs testing CBD as an adjunct treatment for children with treatment-resistant epilepsy were carried out. All of them found the treatment group to show significant reductions in seizure frequency as compared to the placebo group. Since then, more RCTs have been carried out, and more research has been done regarding adults with epilepsy and other non-treatment-resistant epilepsy syndromes.⁹ 

Safety

While the results of the RCTs in seizure frequency seem quite positive, there are many different safety issues yet to be addressed. Firstly, it was found that a high percentage of the participants in these RCTs experience adverse events.⁹ Most of these were described as mild/moderate and tolerable with dosage alterations. Side effects mostly included drowsiness, loss of appetite, vomiting, and diarrhoea.¹² 

There was a small group of people who experienced an increase in serum transaminases, which was deemed a serious side effect due to its possible toxic effect on the liver. Interestingly, it was found that this increase was more common if patients were simultaneously taking CBD and valproate, a common anticonvulsant drug. Due to this, scheduled hepatotoxicity testing is highly recommended if taking this combination.¹²

Other drug interactions include CBD with clobazam. CBD can alter the metabolism of other drugs. This means that taking CBD with specific medication can alter the effect of the latter. This is dangerous because if this interaction is not taken into account, it could lead to toxic doses of medication in the body or the appearance of unwanted side effects.¹² 

It is this lack of information about the drug’s effects and interactions that poses a safety issue and a concern in the eyes of many clinicians and scientists. While the results in trials are valid, it would be unwise to market CBD for a wide range of epilepsy syndromes or other conditions without further characterisation of the drug’s method of action and more safety testing. Furthermore, despite there being a legalised formulation of pure CBD (Epidiolex), some still purchase CBD compounds illegally through different means, which puts the patient at risk as the formulation and quality are not regulated. Some of these can even have THC, which can have an exacerbating effect on epilepsy symptoms.⁹ 

Difficulties with implementation

While the legalisation of CBD for only 2 epilepsy syndromes is understandable due to safety concerns and lack of research, this narrow prescription can be a detriment to those who may benefit from CBD. CBD is already somewhat of a controversial compound due to its ties with cannabis. This, along with the fact that it is only recommended for 2 syndromes and still has room for further research, makes it unlikely that a clinician will prescribe it.⁹ There is a lack of trust and familiarity in CBD, which is partly warranted yet still perhaps excessive. 

Additionally, the only legal formulation of pure CBD is expensive, which can be a huge barrier for many families. Annual treatment of Epidiolex can have a price of between $5k- $83k, depending on weight and dosage.¹³ Due to this, some may turn to illegal products, which have a negative effect on the patient due to a myriad of reasons unrelated to the actual CBD. 

Next steps

In order to properly prescribe CBD for epilepsy and other conditions, it is imperative that further research be done. Below are some of the major factors that need additional investigation:¹²

• Safety testing, including carcinogenicity, toxicity, exposure during pregnancy, etc.
• Long-term effects of prescription
• Research on adults with epilepsy
• Testing for a wider array of epilepsy syndromes
• Dosage testing, as current recommendations seem way below the safely tolerated dosage. 
• Possible tolerance or treatment resistance

Hopefully, further characterisation will improve its standing in the public eye and the healthcare sphere. 

Summary

CBD is a non-psychoactive, non-addictive major component of the cannabis plant. It has gained popularity as a possible medical compound in epilepsy, a common and often chronic condition affecting the brain. Current evidence seems to show a reduction in seizure frequency in treatment-resistant patients when taking CBD as an adjunct to standard treatment. However, these trials also report a higher incidence of mild/moderate side effects, including drowsiness, loss of appetite, vomiting, and diarrhoea.

CBD is currently legalised as a treatment for Lennox-Gastaut and Dravet syndrome by the FDA and EMA. Further research on the nature of CBD and its safety profile is still necessary, as well as more investigation on its possible benefits to other types of epilepsy and many other aspects. Currently, CBD’s only legal formulation is expensive, and clinicians are unfamiliar or distrustful of the compound due to its ties to cannabis. Still, further research will hopefully aid in the proper prescription and formulation of CBD for those who will benefit from it. 

FAQs

What are complementary treatments for epilepsy?

Complementary treatments for epilepsy usually include acupuncture, massage therapy, aromatherapy, exercise, relaxation techniques like yoga and medication, and herbal medicine.¹⁴ In this case, CBD would fall under herbal medicine due to its extraction from the cannabis sativa or cannabis plant.

Has CBD been approved for a type of epileptic seizure?

Currently, CBD has been approved for 2 epilepsy syndromes: Lennox-Gastaut and Dravet syndrome. However, research is currently underway to possibly expand CBD’s prescription.