Cannabis Oil as Add-on Therapy Seen to Ease Severe Seizures in CLN6 Batten

Adding cannabis oil to standard anti-seizure medications may be an effective way of managing treatment-resistant status epilepticus — life-threatening seizures that require urgent medical treatment — in people with CLN6 Batten disease, a case report suggests.

This case adds to similar reports, and supports increasing evidence highlighting the potential anti-seizure efffects of cannabis-based compounds.

Still, more research is needed to confirm the safety and effectiveness of cannabis oil in treatment-resistant status epilepticus, and in reducing overall seizures in this patient population, the researchers noted.

The case study, “Successful Treatment of Super-Refractory Status Epilepticus With Cannabis Oil in a Patient With Neuronal Ceroid Lipofuscinosis,” was published in the Journal of Neurology Research.

Batten disease, also known as neuronal ceroid lipofuscinosis (NCL), is the most common group of pediatric neurodegenerative disorders. It is divided in different types, caused by mutations in at least 14 different genes.

Seizures are common among all types of Batten disease. Those lasting more than five minutes, or consecutive seizures without recovery of consciousness separating them, are defined as status epilepticus. When this status continues for at least 24 hours despite anesthesia, or recurs after its withdrawal, it is called super-refractory status epilepticus. Both these statuses are life-threatening and require urgent medical attention.

Anti-seizure medications are not always effective, and increasing evidence suggests that cannabis-based agents, including cannabis oil, may help drop seizure frequency. These benefits are thought to be associated with cannabis’ major non-psychoactive active component, cannabidiol (CBD) — suggested to have anti-seizure, anti-inflammatory, antioxidant, neuroprotective, and immunomodulatory properties.

Epidiolex, a purified oral form of CBD by GW Pharmaceuticals, was the first cannabis-based medicine to be approved in the U.S. and Europe to treat seizures associated with two severe childhood epilepsies:  Lennox-Gastaut syndrome and Dravet syndrome. However, no cannabis-based compounds have been approved for Batten disease to date.

Researchers at the University of Nicosia Medical School, in Cyprus, reported the case of a 25-year-old man with CLN6 Batten disease — also known as variant late infantile NCL6 disease — whose super-refractory status epilepticus was successfully managed after adding cannabis oil to standard anti-seizure medication.

Of note, cannabis oil contains both CBD and THC, the cannabis plant’s psychoactive component.  Since it is not approved to treat seizures, cannabis oil acquisition is made through “marijuana dispensaries which creates discrepancies in dosing and CBD/THC ratios,” the researchers wrote. Its use is therefore controversial.

The patient’s seizures started at the age of 10 and progressively became treatment-resistant, requiring the use of a number of anti-seizure medications that included a combination of Keppra (levetiracetam), Lamictal (lamotrigine), lacosamide, and piracetam.  

Genetic testing confirmed the presence of two new mutations — c.407G>A and c.884 A>G — in CLN6, the gene that is deficient in CLN6 Batten disease. Further testing of his closest family members found that the c.407G>A mutation was inherited from his mother, and the other appeared for a first time in the patient, without being inherited from either parent.

At age 25, his seizures progressed to super-refractory status epilepticus, which was resistant to phenobarbital, clobazam, valproic acid (sodium valproate), phenytoin, Keppra, and zonisamide. 

He was admitted to the intensive care unit and put in an anesthesia-induced coma for several weeks, since any attempt to reduce or reverse it resulted in the re-emergence of status epilepticus. 

A trial of cannabis oil, in addition to anti-seizure medication, was initiated with signs of improvement. Over the following two weeks, the man was tested on a combined form of CBD and THC, which resulted in a significant drop in seizures. It also allowed anesthesia medication to be withdrawn completely after 50 days in a coma, and a full week without epileptic episodes. 

The man was discharged home four weeks after his anti-seizure medications and daily intake of the CBD/THC combination were lowered.

Eight months later (the last reported assessment), he was experiencing a significant drop in seizure frequency and had stopped using clobazam and zonisamide. He continued with a treatment regimen combining cannabinoid oil and low-dose phenobarbital, valproic acid, and Keppra.

“Although this case has shown that it is beneficial in reducing the seizures in NCL, future studies are required to test the efficacy and safety of cannabis oil as well as to define a recommended ratio of CBD/THC to be trialed in [treatment]-resistant status epilepticus,” the researchers wrote.