Three studies presented at the American Epilepsy Society's 69th Annual meeting demonstrated promising efficacy and safety data for a liquid formulation of a type of cannabinoid known as cannabidiol (CBD). And a fourth study shows the importance of the possible interactions of CBD with existing antiepileptic drugs in a mouse model.
Two particular forms of epilepsy, Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS), are resistant to currently used epilepsy drugs, making CBD a possible substitute.
The largest CBD study presented at the meeting involved the efficacy and safety of GW Pharmaceutical's investigational cannabidiol medicine, Epidiolex, which was tested in an open-label Expanded Access programs at 16 sites. The study includes 261 people, the majority of which are treatment-resistant children with severe epilepsy. After three months of treatment with CBD the number of seizures per participants was reduced by a median of 45%. DS patients recorded a 62% reduction in seizures and 13% were seizure-free, while LGS patients showed a 71% reduction in atonic seizures. Importantly, serious adverse events were present in 34% of participants and 12% withdrew from the study because of a lack of efficacy.
Lead author Orrin Devinsky of New York University Langone Medical Center's Comprehensive Epilepsy Center said that "We are pleased to report these promising data on significant numbers of children. These data reinforce and support the safety and efficacy we have shared in previous studies. Most importantly it is providing hope to the children and their families who have been living with debilitating seizures."
Though these results appear promising, especially in DS and LGS patients, he adds that "these results are from an uncontrolled study. Further study is needed before results can be confirmed. Randomized controlled studies are now underway to help us better understand the effectiveness of the drug. We very much look forward to the results from these studies during 2016."
Following on from the current interest in Epidiolex, Michael Oldham of the University of California, San Francisco, presented some work on the long-term efficacy of the drug. This study administered CBD to 26 patients parallel to their regular AED regimen for a year. They found that the addition of daily CBD to the patients drug regimen reduced the number of seizures by half for 10 participants (40%), with one remaining seizure-free.
On the other side, 12 participants didn't respond at all to the drug and therefore discontinued the study while one suffered a marked increase in seizure activity due to CBD.
"The CBD as an add-on therapy reduced seizures by half for a third of the patients in the first 12 weeks of the study," Oldham said. "This substantial improvement was maintained by 40 percent of participants for the entire 12-month period showing strong promise that CBD can be effective in controlling seizures."
Another study conducted at the University of Utah with, describes their findings from a project that looked at the anticonvulsant and tolerability profile of CBD in animal models. Using four well established acute seizure models, they tested CBD using the Anticonvulsant Screening Program (ASP) with help from the National Institute of Neurological Disorders and Stroke ASP and found significant anticonvulsant effects in addition to being well tolerated.
The last study of note, also conducted at the University of Utah but this time by Misty Smith's group, described how CBD interacts with five different AEDs in animal models. The interactions between CBD and current AED drugs is important when deciding whether to co-prescribe the drug for the patient. They found a significant synergistic effect of administering CBD with levetiracetam and an antagonistic effect with some of the fixed dose-ratio combinations of CBD with clobazam and separately with carbamazepine.
"By identifying the synergistic, additive or antagonistic interactions between CBD and other ASDs, we are gaining a better understanding of the nature of these interactions. This will help optimize therapeutic safety and efficacy for CBD going forward," said Smith.