Update: Cannabis for Epilepsy Treatment

Medical marijuana for the treatment of epilepsy has received a great deal of attention in the press over the past few years from parents and advocates that support its use. Thus far, there is little objective data. Parental reports and news interviews provide some anecdotal stories of parents seeking cannabis for treatment of their children's epilepsy, while there is a dearth of reports or data on how to calculate dose per weight or optimal method of delivery for children. 

Certainly the current treatment options for epilepsy are not adequate to control the disease for far too many patients. The variation in forms of epilepsy presents a challenge as well, because while the list of anticonvulsants may appear sufficient, many anticonvulsants are effective only for generalized seizures or frontal lobe seizures or temporal lobe seizures, but not the other types. Patient tolerability and drug interaction is a considerable concern in the management of epilepsy and in the quality of life of patients living with epilepsy. 

Few controlled research studies have evaluated objective measures of efficacy and side effects of cannabis for epilepsy treatment. One retrospective chart review evaluated 75 patients who had been treated with oral cannabis extracts for refractory seizures. Patients had been diagnosed with either Lennox-Gastaut syndrome, a notoriously treatment resistant, refractory form of childhood epilepsy usually associated with cognitive deficits or Dravet syndrome, a severe form of infantile spasms associated with cognitive and behavioral delay. 

The chart review showed that 33% of parents reported a greater than 50% reduction in seizure frequency. There were also parental reports of between 10% to 33% of improved alertness, language, and motor skills. This can be explained by the decline in generalized seizures that typically result in lack of alertness. But the seizure-free periods may also have contributed to progress in cognitive and behavioral development. 

Side effects were significant, however, with 44% of parents reporting increased seizures, fatigue, status epileptics, intubation, and even death. The dose of each child's cannabis treatment was not available. 

Another, larger open-labeled trial evaluated 135 patients, also with severe childhood onset, intractable, treatment-resistant epilepsy. Almost half of the patients were diagnosed with either Lennox-Gastaut or Dravet syndrome. Results of the prospective 12-week study were similar to those of the retrospective chart review, showing about a 35% improvement in seizure frequency and a 79% frequency of adverse events, of which 30% were deemed serious – including sudden death. 

The prospective study used oral cannabidiol at 2-5mg/kg per day titrated to a maximal dose of 25mg/kg per day or 50 mg/kg per day. 

Given the initial results, it appears that some forms of cannabis may be useful for selected types of refractory epilepsy. However, with the prevalence of serious adverse effects, future research would be more likely directed to determining the mechanism of action and at isolating the effective components of cannabis, a complex chemical, in order to define whether efficacy can be optimized while minimizing adverse events.

Do you take care of refractory epilepsy patients in your practice? What side effect profile do you consider acceptable for intractable seizures?

References:

Press CA, et al. Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy. Epilepsy Behav. 2015 Apr;45:49-52.

Devinsky O, et al. Cannabidiol in patients with treatment-resistant epilepsy: an open-label interventional trial. Lancet Neurol. Epub 24 Dec 2015.