CBD and Epilepsy

Exploring Drug–Drug Interactions with Epilepsy Treatments when Combined with Cannabidiol in Patients with Epilepsy

As medical cannabis products have gained increasing attention throughout the world, and particularly in the UK, perhaps one of the most discussed areas of research is that of the potential of cannabinoids in Epilepsy treatments.

In 2018, the government rescheduled cannabis following in response to evidence presented by the Chief Medical Officer at the time, Dame Sally Davies. Soon afterward, Epidyolex, cannabidiol (CBD) isolate, was licensed for use in treatment-resistant epilepsy syndromes (Lennox-Gastaut and Dravet).

Past trials have assessed the potential of CBD in treating epilepsy-related seizures, and many have demonstrated positive results. However, one of the factors that should be considered when using CBD is its potential interactions with other drugs. A recent study aimed to assess how the cannabinoid may interact with common Epilepsy treatments in comparison to placebo.

CBD as an Adjunct Therapy

Studies assessing CBD with clobazam in treating epilepsy in Lennox-Gastaut and Dravet syndromes have demonstrated a reduction in seizure burden. Additionally, CBD has demonstrated a favourable safety profile. When CBD is initiated in children with these syndromes it is added into a regimen that already contains one or more anti-epilepsy drugs. Indeed, Epidyolex is only licensed to be used in addition to clobazam for these syndromes.

When CBD is administered as an adjunct therapy, it is crucial that drug-to-drug interactions are carefully monitored and understood to ensure the safety of the patients. When administered alongside other medications, the treatments can potentially become less effective or even harmful.

What were the findings?

In order to assess the interaction between CBD and existing epilepsy medications, researchers designed a phase II, two-arm, parallel-group, double-blind, randomized, placebo-controlled trial. In practice, this means that participants were given common epilepsy medications, stiripentol, and valproate alongside either Epidyolex or a placebo.

Patients in the CBD groups were given a pre-determined safe dose of 20mg/kg/day of Epidyolex alongside either stiripentol or valproate. Concentrations of the epilepsy medications were then monitored.

The study found that CBD exposure led to an increase in stiripentol within patient blood samples. In patients given Epidyolex in conjunction with valproate, the metabolism of valproate or its active metabolites were not observed to be affected.

A significant number of patients in the CBD groups reported adverse effects throughout the treatment period. However, the adverse effects tended to be mild, including diarrhoea and nausea. Researchers concluded that the clinical relevance of the increase in stiripentol exposure is unknown and stress that patients prescribed this combination of pharmaceuticals should be monitored for adverse reactions.