By: Anup Patel MD, Elaine Kiriakopoulos MD, MSc
07/2018

The use of cannabis to treat epilepsy and other neurological conditions has been studied for a number of years. It has been hotly debated too.

On June 25, 2018, the U.S. Food & Drug Administration (FDA) approved EPIDIOLEX (cannabidiol, CBD) oral solution for the treatment of seizures associated with two epilepsy syndromes - Lennox-Gastaut syndrome and Dravet syndrome - in people two years of age or older. Epidiolex represents a new medication option for children with these types of epilepsy. It is also the first ever FDA approved medication to treat seizures in Dravet syndrome.

What does FDA approval of Epidiolex (CBD oral solution) mean?
The FDA approval and Drug Enforcement Administration (DEA) scheduling of Epidiolex brings to market the first plant-based drug derived from the cannabis plant in the U.S.

What is medical cannabis?

Cannabis is known by many names - the most common is marijuana. Cannabis is the Latin name used most often by botanists and pharmaceutical companies. The word marijuana usually refers to the leaves and female flowers of the cannabis plant. Medical cannabis is whole plant marijuana or chemicals in the plant used for medical purposes.

Cannabinoids are substances in cannabis that act on cells in the body (called cannabinoid receptors) to cause some effect. Two major ingredients include

Tetrahydrocannabinol, or THC, which causes the psychoactive effects of "getting high"
Cannabidiol, or CBD, which does not cause psychoactive effects but has shown some positive effects on certain body systems. This is the part that has been effective in reducing seizures in some people with epilepsy.

Does cannabis help seizures?

Early evidence from laboratory studies, anecdotal reports, and small clinical studies over a number of years suggest that cannabidiol (CBD) could potentially help control seizures. Research on CBD has been hard to do and taken time due to federal regulations and limited access to cannabidiol. There are also many financial and time constraints. In recent years, a number of studies have shown the benefit of specific plant-based CBD product in treating specific groups of people with epilepsy who have not responded to traditional therapies.

What do I need to know about hemp?

Hemp is a variety of Cannabis Sativa L. plant historically grown for fibrous materials found in its stalks and seeds. It has been used to make items such as clothing fiber, upholstery, and other household items.

Hemp traditionally contains lower concentrations of THC and higher levels of CBD. Cannabinoids extracted from hemp plants, including CBD, have until recently been classified as marijuana and considered Schedule I substances. Per the DEA, Schedule I substances currently have no accepted medical use and have a high potential for abuse. A federal law* enacted in December 2018, however, reclassifies hemp and hemp-derived CBD as an agricultural commodity and exempts it from the list of Schedule I Drugs.

Despite this change in the classification of hemp and hemp-derived CBD, the only CBD product that has been rigorously studied and approved to be used as a medical therapy for epilepsy is the drug Epidiolex. While more CBD products may come to market in the coming months, it is important to understand that not every CBD product is the same quality or uniform from batch to batch. Any drug or supplement that is being considered for use as a medical treatment should first be discussed with your doctor. The potential for benefit as well as the interaction with other seizure medications and possible side effects require careful review with your doctor.

*The Agriculture and Nutrition Act of 2018 (H.R. 2) legalizes hemp and hemp-derived CBD. The bill changes the definition of hemp to encompass any plant or product derived from the plant that contain less than 0.3% THC by dry weight and classifies them as exempt from the controlled substance restrictions applied to marijuana. The law further amends the Controlled Substances Act to exempt hemp from Schedule I drugs.

What studies exist to support the use of CBD in epilepsy?

Epidiolex (Cannabidiol, CBD)
Studies in the U.S. of Epidiolex (a plant-based CBD formulation) have been ongoing for a number of years. Data from these studies has helped provide evidence that led to the FDA approval of this product on June 25, 2018.

Epidiolex is a purified (> 98% oil-based) CBD extract from the cannabis plant. It is produced by Greenwich Biosciences (the U.S. based company of GW Pharmaceuticals) to give known and consistent amounts in each dose.

Researchers studied this medicine in controlled clinical trials. These studies used a control group with some people taking a placebo while others were given CBD at different doses. Researchers did not know who was getting the placebo and who was getting CBD. These tpyes of studies are called “gold standard” studies.

A summary of the Epidiolex clinical trials is found below:

- In controlled and uncontrolled trials in people with Lennox-Gastaut syndrome (LGS) and Dravet syndrome, 689 people were treated with Epidiolex (CBD), including 533 people treated for more than 6 months and 391 people treated for more than 1 year.

- In an expanded access program and other compassionate use programs, 161 people with Dravet syndrome and LGS were treated with Epidiolex, including 109 people treated for more than 6 months.

- All study participants were taking other seizure medications.

- In controlled trials, the rate of stopping the medicine due to any side effect was small and happened most in people taking the higher dose of Epidiolex.

- The most frequent cause of stopping treatment with Epidiolex was a change in liver function.

- Sleepiness, sedation, and lethargy led to stopping Epidiolex in 3% of people taking the higher dose.

- The most common side effects were sleepiness, decreased appetite, diarrhea, change in liver function, fatigue, malaise, asthenia (weakness or lack of energy), rash, insomnia, sleep disorder, poor quality sleep, and infections.

Does cannabis have side effects?

Marijuana or cannabis in general has a number of side effects depending on how it is used. For example, if smoked, the negative effect of smoking on a person’s lungs and heart also apply to marijuana.

It is important to know that even though marijuana is a plant, it is broken down in a person’s liver like many medicines. People mistakenly believe that marijuana is completely safe because it is a plant or oil from a plant. However, medication interactions can occur.

The safety data from the trials in people with Lennox-Gastaut syndrome and Dravet syndrome has shown similar side effects. Tiredness, diarrhea, and upset stomach are reported the most. Interestingly, people getting the placebo also reported diarrhea and upset stomach feeling as well. This may be due to both products being oil.