Welcome to Study of the Week from Patient Worthy. In this segment, we select a study we posted about from the previous week that we think is of particular interest or importance and go more in-depth. In this story we will talk about the details of the study and explain why it’s important, who will be impacted, and more.

If you read our short form research stories and find yourself wanting to learn more, you’ve come to the right place.

This week’s study is…

Medical cannabis for severe treatment resistant epilepsy in children: a case-series of 10 patients

We previously published about this research in a story titled “Whole-Plant Medicinal Cannabis Found to be Superior to CBD as Treatment for Childhood-Onset Epilepsy,” which can be found here. The study was originally published in the journal BMJ Paediatrics. You can view the full text of the study here.

What Happened?

In recent years, the medicinal uses of the cannabis plant have gained more and more attention among the health and medical community. Much of this attention has focused on cannabidiol (CBD), a compound found in the plant. Some research has suggested that CBD may have several health benefits, such as treatment of anxiety, pain, cognition, and disorders such as epilepsy. This has culminated in the approval of Epidiolex, a form of CBD that was approved in 2018 for the treatment of two rare childhood epilepsies: Dravet syndrome and Lennox-Gastaut syndrome. However, a small number of these patients do not benefit from the treatment. This study sought to determine if whole plant cannabis could help treat seizures in patients that failed to respond to Epidiolex and other therapies.

This study evaluated ten children with epileptic disorders that had failed to respond to conventional approaches and, in some cases, CBD. This was a retrospective study, and the patients were recruited from two different charities; all were 18 years or younger, with an average age of six years. A range of whole plant cannabis oils were used for treatment and dosage levels were determined by the individual physician treating each patient. The primary outcome measure in this study was frequency of seizures.

This study found that treatment with whole-plant cannabis oil was able to reduce the frequency of seizures by 86 percent. Patients in this study were able to reduce their use of other treatments from an average of seven treatments down to just one. Seven of the children stopped using other approaches entirely. On average, the patients were dosed daily with an average of 171.8 mg of CBD and 5.15 mg of tetrahydrocannabinol (THC), the compound in cannabis most responsible for the psychoactive effect experienced by recreational users.

Along with a drop in seizure frequency, parents and caregivers also reported other improvements in overall behavior, cognition, eating, and sleep. Only minor side effects were reported. The average monthly cost of treatment (obtained from private sources) was £874. Limitations of this case study include its retrospective and observational nature, small number of patients, and reliance on caregiver recall. 

About Rare Childhood Epilepsies

There are a significant number of disorders that can cause epilepsy in childhood. For the sake of simplicity, we will discuss two of the most well known disorders here: Dravet syndrome and Lennox-Gastaut syndrome.

Dravet syndrome is a form of severe epilepsy that usually begins by the sixth month of life. The disease is most characterized by frequent seizures that are sometimes triggered by fever or hot temperatures. In most cases, the syndrome is caused by mutations of the SCN1A gene. Most of the time, these mutations are not heritable and appear spontaneously. The predominant symptom of Dravet syndrome is seizures; varying types of seizures often occur as the disorder progresses, as well as ataxia, developmental delays, behavioral disorders that may resemble autism, and cognitive impairment. Seizures can be potentially lethal. Management strategies for Dravet syndrome may include a ketogenic diet, anticonvulsant medications, cognitive rehabilitation therapy, and cannabidiol. This rare disorder is estimated to appear anywhere from 1 in every 20,000 to 1 in every 40,000 births. To learn more about Dravet syndrome, click here.

Lennox-Gastaut syndrome is a rare and severe form of childhood epilepsy. The disease is most characterized by cognitive dysfunction and frequent seizures of varying types. The syndrome appears to have a variety of causes, such as certain genetic mutations, brain tumors, and congenital infections. It also may appear alongside genetic disorders such as tuberous sclerosis. With symptoms first appearing at around 3-5 years, most patients continue to face seizures for much of their lives. Tonic seizures are the most common. Other symptoms include status epilepticus, vision problems, and slow spike waves on electroencephalograms (EEG). Treatment may include a variety of medications, but Lennox-Gastaut syndrome rarely responds strongly to typical antiseizure drugs. Other approaches may include a ketogenic diet and certain surgical operations. The syndrome is considered responsible for around four percent of epilepsy cases in children. To learn more about Lennox-Gastaut syndrome, click here.

Why Does it Matter?

While medical whole plant cannabis was cleared as a prescriptible therapy for severe childhood epilepsy in 2018 in the UK, most doctors are hesitant to use it due to a lack of confirmatory data in the clinical trial setting. While this small-scale study is hardly on the same level as a controlled clinical trial, the findings nevertheless suggest that more research into the use of whole plant cannabis extracts for the treatment of epilepsy is warranted. Only three prescriptions of whole plant cannabis have been ordered to date through the National Health Service (NHS).

It’s unclear why whole-plant cannabis can work in instances where CBD alone does not, but perhaps the combination of cannabinoids found in whole-plant extracts potentiate or synergize with each other. The authors state that more research will be needed to understand the differences. While physicians have expressed reservations about whole-plant cannabis, the National Institute for Health and Clinical Excellence (NICE) recently stated that it would be open to accept case studies and real world data as valid evidence for the effectiveness of a given treatment.

“We believe that our data on whole-plant medical cannabis in childhood-onset severe treatment-resistant epilepsy provides evidence to support its introduction into the NHS within current NICE prescribing guidelines … Such a move would be hugely beneficial to the families, who in addition to having the psychological distress of looking after their chronically ill children, have also to cover the crippling financial burden of their medication.”