Cannabidiol Manages Seizures in Patients with Lennox-Gestaut Syndrome

by | Aug 16, 2018 | 2018, Alternative Therapies, Brain Health, CBD

Written by Angeline A. De Leon, Staff Writer. A fourteen-week treatment of 20 mg/kg daily of a pharmaceutical formulation of purified cannabidiol significantly diminished drop seizures in the participating patients with Lennox-Gastaut syndrome compared to the control group.

Lennox-Gastaut Syndrome is a rare, severe form of epileptic encephalopathy beginning in early childhood and involving multiple types of seizures. Affected children (typically by 8 years of age) experience the occurrence of atonic, tonic, and atypical absence seizures, as well as drop attacks involving sudden falls due to seizures 1. In addition, children with Lennox-Gastaut typically develop cognitive dysfunction and significant behavioral problems. Reports show that while up to 60% of patients will suffer from cognitive impairment at disease onset, up to 95% will go on to develop cognitive dysfunction with increasing age 2. Treatment for the disease remains limited and currently involves a variety of anticonvulsant and sedative medications such as felbamate and clobazam 3. In some patients, non-pharmacological treatments such as a ketogenic diet and vagus nerve stimulation 4,5 have proven somewhat effective. However, with existing treatments, less than 10% of patients show complete remediation of seizures 6. Although untested in patients with Lennox-Gastaut syndrome, cannabidiols have shown promising efficacy against seizures in both in vitro and in vivo models 7. For example, results from a randomized controlled trial in children with Dravet syndrome, a disease involving intractable epilepsy beginning in infancy, demonstrated cannabidiol to be a safe and effective treatment. In an effort to extend the potential therapeutic benefits of cannabidiol to patients with Lennox-Gastaut syndrome, researchers conducted an investigation examining the efficacy and safety of cannabidiol as an adjunctive therapy to existing anti-epileptic drugs.

Using a randomized, double-blind, placebo-controlled trial design, a total of 171 patients (aged 2-55 years) with a clinical diagnosis of Lennox-Gastaut syndrome (involving more than one type of generalized seizure for at least 6 months, at least two drop seizures per week, and resistance to treatment from at least two forms of anti-epileptic medication) were recruited across 24 clinical sites in the U.S., Netherlands, and Poland. Patients were stratified by age group and randomly allocated to orally receive either cannabidiol (20 mg/kg of a pharmaceutical formulation of purified cannabidiol) or identical placebo daily for 14 weeks. Following randomization, patients were assessed on days 15, 29, 57, and 99 and evaluated on percentage change in monthly frequency of drop seizures during the treatment period.

Findings revealed that over the course of the 14-week treatment period, monthly frequency of drop seizures diminished by a median of 43.9% (from a median of 71.4 to 31.4 drop seizures per patient per month) in the cannabidiol group and by a median of 21.8% (from a median of 74.7 to 56.3 drop seizures per patient per month) for the placebo group, with an estimated median difference of –17.21 between treatment groups (95% Confidence Interval: -30.32 to –4.09, p = 0.0135). Researchers also reported that 44% (38 of 86) of patients in the cannabidiol group vs. 24% (20 of 85) of patients in the placebo group experienced a diminishment of 50% or more in drop seizure frequency from baseline to the end of treatment (Odds Ratio = 2.57, 95% CI: 1.33 to 4.97, p = 0.0043). In addition, over the course of 14 weeks, monthly frequency of total seizures decreased by a median of 41.2% (from a median of 144.6 to 83.8 seizures per month) for the cannabidiol group and by a median of 13.7% (from a median of 176.7 to 128.7 seizures per month) for placebo, with an estimated median difference of –21.1 between treatment groups (95% CI: -33.3 to –9.4, p = 0.0005).

Overall, evidence from the first randomized, double-blind trial using cannabidiol as a complementary therapy for seizure control in patients with Lennox-Gastaut syndrome suggests cannabidiol to be a safe and effective therapy option for this highly treatment-resistant population. Cannabidiol appears to be successful in reducing not only drop seizures, but total seizures overall in patients with Lennox-Gastaut, making it a promising candidate as an adjunct therapy to current anti-epileptic medication. Findings warrant further replication in a longer-term study.

Source: Thiele EA, Marsh ED, French JA, et al. Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomized, double-blind, placebo-controlled phase 3 trial. The Lancet. 2018; 391(10125): 1085-1096. DOI: 10.1016/S0140-6736(18)30136-3.

 Posted August 16, 2018.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

References:

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