About one-third of patients who used cannabidiol (CBD) to manage treatment-resistant epilepsy developed tolerance to it, researchers from Israel reported here.

In a study of 92 children and young adults with treatment-resistant seizures who used cannabis oil extract for an average of 19.8 months, tolerance to CBD emerged in 32.6% of patients, reported Shimrit Uliel-Sibony, MD, of Tel Aviv Sourasky Medical Center’s Dana Children’s Hospital, and colleagues at the American Epilepsy Society annual meeting.

In the U.S., the FDA has approved a purified, pharmaceutical-grade formulation of cannabidiol (Epidiolex), a chemical component of the Cannabis sativa plant, for children with Lennox-Gastaut and Dravet syndromes.

In this prospective study, Uliel-Sibony and colleagues followed patients in Tel Aviv, ages 1-37 years (average age 11.8) from 2014 to 2017 with treatment-resistant epilepsy of various etiologies, ranging from Dravet syndrome and Lennox-Gastaut syndrome to epilepsy caused by stroke. All patients subsequently had been treated with one of two strains of CBD-enriched cannabis oil extract that had a 20:1 CBD-to-tetrahydrocannabinol (THC) ratio.

The researchers defined tolerance as either the necessity to increase dose by ≥30% after efficacy declined, or a response reduction of >30%. They saw tolerance in 30 patients, on an average dose of 12.6 mg/kg/day. The mean time until tolerance appeared was 7.3 months (range 1-24 months).

The researchers increased the CBD dose in most patients who developed tolerance; 12 patients achieved their previous response level and 15 did not.

“This study found that tolerance develops in one-third of patients with treatment-resistant epilepsies who showed an initial reduction in seizures to a high CBD/low THC product after 7 months,” Devinsky told MedPage Today. “The observation that two-thirds of patients did benefit over a long follow-up period is a key finding.”

There was no statistically significant correlation between patient’s age and tolerance, but patients with shorter epilepsy duration showed a higher tendency to develop tolerance, Uliel-Sibony’s group noted. Predictive factors and mechanisms are unknown, and long-term studies to better characterize the long-term efficacy and safety of CBD are needed, they added.

SOURCE: MedPageToday.com by J. George with Primary Source American Epilepsy Society


Source Reference: Uliel-Sibony S, et al “Cannabidiol tolerance in children and adults with treatment-resistant epilepsy” AES 2018; Abstract 2.233.