Tolerance to Cannabidiol for Treatment-Resistant Epilepsy Seen Over Time

Tolerance to cannabidiol may exist, potentially limiting its efficacy as an antiseizure therapy in the long-term management of epilepsy.
The following article is part of conference coverage from the American Epilepsy Society’s Annual Meeting in New Orleans, LA. The Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from AES 2018.

NEW ORLEANS — Findings from a study showed tolerance to cannabidiol exists which may limit its efficacy as an antiseizure therapy in the long-term management of epilepsy. The data were presented at the 72nd American Epilepsy Society Annual Meeting, held November 30 to December 4, 2018.

“CBD is a good option for children and adults with certain kinds of epilepsy, but as with anti-epileptic drugs (AEDs), it can become less effective over time and the dose may need to be increased to manage the seizures,” said Shimrit Uliel-Sibony, MD, lead author of the study and head of the pediatric epilepsy service at Tel Aviv Sourasky Medical Center’s Dana-Dwek Children’s Hospital, Israel.

Dr Uliel-Sibony and colleagues aimed to evaluate the rate of tolerance to cannabinoids in the treatment of epilepsy among children and adults. They conducted a prospective review (N=92) of patients aged 1 to 37 years (mean age 11.8 years) who had treatment-resistant epilepsy from March 2014 to September 2017.

In the study, tolerance was defined as either the need to increase medication dose 30% or more after reduction of efficacy, or a 30% or more decrease in response leading to increased seizures.

Study patients were given cannabis oil extract (CBD:THC ratio 20:1) for a mean 19.8 months. A 50% reduction in average monthly seizure frequency was seen in 57% (n=53) of patients, demonstrating treatment efficacy. Tolerance, however, was seen in nearly one-third of those patients (32% [n=17]) after an average of 7.3 months (range 1 to 24 months) at an average dose of 12.6 mg/kg daily.

After a dose increase to overcome the effect of tolerance, 12 patients achieved their previous response level and 15 patients reported a “satisfying but less than prior response level.” Further, about one-third of patients discontinued CBD therapy due to lack of efficacy or due to adverse events, which included sleepiness and gastrointestinal issues.

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Uliel-Sibony S, Hausman-Kedem M, Kramer U. Cannabidiol Tolerance in Children and Adults With Treatment-Resistant Epilepsy. Presentation at: 72nd Annual Meeting of the American Epilepsy Society; November 30-December 4, 2018; New Orleans, LA. Abstract 2.233.