Parental reporting of response to oral cannabis extracts for treatment of refractory epilepsy

Highlights

• Parents in our study reported a 33% response to OCE.

• Relocating to Colorado had a significant effect on response rates.

• The response rate is similar to previously reported placebo response rates.

• Reported response was not correlated with improved background EEG data.

• Parents reported a variety of additional benefits of OCE and adverse reactions.

Abstract

Objective

Oral cannabis extracts (OCEs) have been used in the treatment of epilepsy; however, no studies demonstrate clear efficacy. We report on a cohort of pediatric patients with epilepsy who were given OCE and followed in a single tertiary epilepsy center.

Methods

A retrospective chart review of children and adolescents who were given OCE for treatment of their epilepsy was performed.

Results

Seventy-five patients were identified of which 57% reported any improvement in seizure control and 33% reported a > 50% reduction in seizures (responders). If the family had moved to CO for OCE treatment, the responder rate was 47% vs. 22% for children who already were in CO. The responder rate varied based on epilepsy syndrome: Dravet 23%, Doose 0%, and Lennox–Gastaut syndrome (LGS) 88.9%. The background EEG of the 8 responders where EEG data were available was not improved. Additional benefits reported included: improved behavior/alertness (33%), improved language (10%), and improved motor skills (10%). Adverse events (AEs) occurred in 44% of patients including increased seizures (13%) and somnolence/fatigue (12%). Rare adverse events included developmental regression, abnormal movements, status epilepticus requiring intubation, and death.

Significance

Our retrospective study of OCE use in pediatric patients with epilepsy demonstrates that some families reported patient improvement with treatment; however, we also found a variety of challenges and possible confounding factors in studying OCE retrospectively in an open-labeled fashion. We strongly support the need for controlled, blinded studies to evaluate the efficacy and safety of OCE for treatment of pediatric epilepsies using accurate seizure counts, formal neurocognitive assessments, as well as EEG as a biomarker. This study provides Class III evidence that OCE is well tolerated by children and adolescents with epilepsy.

Introduction

Epilepsy affects over 65 million people worldwide and approximately 2.3 million in the United States [1]. Approximately 1/3 of those have medically refractory epilepsy. Despite decades of research and the continued discovery of new antiseizure medications, seizures in many patients remain unresponsive to medical therapy. Many families choose to try nonpharmaceutical or alternative therapy options. Recently, there has been a surge of interest in the use of marijuana or Cannabis sativa and its extracted components. This interest has been fueled in part by recent media coverage of a specific strain of Cannabis reported to be high in cannabidiol (CBD) that is thought to be less psychoactive than strains containing higher levels of Δ⁹-tetrahydrocannabinol (Δ⁹-THC), the major psychoactive component of cannabis.

A recent review analyzed four controlled studies which evaluated the role of CBD in seizure treatment, all of which had significant methodological flaws, and no benefit of CBD could be identified [2]. In a recent survey of parents of 19 children who were given CBD, more than 50% reported a dramatic decrease in seizures with no severe side effects [3]. There is also evidence that chronic marijuana use leads to a decline in cognitive function that may not be reversible [4], [5].

Following favorable media coverage, OCE use has increased significantly in Colorado (CO). As part of the legislation, patients must have established residency in CO prior to initiating OCE treatment, leading to many patients moving from other states to establish care. The experience of a cohort of pediatric patients with epilepsy who were given OCE is reported.