The United States FDA has approved cannabidiol (Epidiolex® by GW Pharmaceuticals), a non-psychoactive cannabinoid, for the treatment of the severe childhood seizure disorders Dravet Syndrome and Lennox-Gastaut Syndrome. – June 25th, 2018
~ Cannabidiol (Epidiolex®) ~
Cannabidiol (CBD, Epidiolex®) is approved for the prevention of seizures in patients aged 2 years and older with Lennox-Gastaut Syndrome and Dravet Syndrome.
The precise mechanism of CBD in controlling epileptic episodes is not fully understood. It is believed to modulate several endogenous neuronal systems including GABA receptors, TRP-V channels, the voltage-dependent anion channel (VDAC), and the G-protein coupled receptor GPR55. CBD does not appear to interact with the cannabinoid receptors CB1 and CB2 at physiologically relevant concentrations.
Administration and Dosing
Recommended starting dose is 2.5 mg/kg PO BID; may titrate up to 10 mg/kg PO BID if necessary. Monitor serum ALT/AST during course of treatment.
Transaminase Elevations, especially w/ concomitant valproate or clobazam (Label Warning. >10% in clinical trials*)
Anemia (>20% in clinical trials)
Suicidal thoughts & behavior (estimated 0.43%)
Weight Loss (>5% in clinical trials)
Somnolence (>10% in clinical trials)
Malaise/Fatigue/Asthenia (>10% in clinical trials)
Sleep Disturbance (>10% in clinical trials)
GI Distress (>10% in clinical trials)
Rash (>10% in clinical trials)
Infections (>10% in clinical trials)
*all doses, % increased incidence relative to placebo
Contraindications & DDI
Hypersensitivity to CBD
Pregnancy Category C (evidence of fetal harm from animal studies, benefits may outweigh risks)
~ Evidence-Basis ~
CBD in Dravet Syndrome
FDA approval of CBD for Dravet syndrome was based on one randomized, double-blind placebo-controlled trial.
Trial 1: 120 patients 2-19 years old 20 mg/kg CBD PO QD, primarily as add-on therapy to other antiepileptics. Median decrease in seizure frequency 39% in CBD group vs. 13% in placebo group.
CBD in Lennox-Gastaut
CBD effectiveness in Lennox-Gastaut was demonstrated in two randomized double-blind placebo-controlled trials.
Trial 1: 171 patients, 20 mg/kg/day CBD; primarily as add-on therapy to other antiepileptic medications. Median decrease in drop seizure frequency 41% in CBD group vs. 14% in placebo group.
Trial 2: 225 patients, 10 or 20 mg/kg PO daily CBD, median decrease in drop seizure frequency 36-38% in CBD group vs. 18% in placebo group.
~ What is Dravet Syndrome? ~
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Dravet syndrome is an epileptic encephalopathy characterized by febrile seizures beginning in the first year of life. It is commonly caused by loss-of-function mutations in the neuronal voltage-gated sodium channel NaV1.1, and occurs in 2-5 per 100,000 individuals. Seizures in Dravet syndrome are often treatment resistant. Behavioral problems, developmental delays, and cognitive deficits are also commonly observed in patients with Dravet Syndrome.
~ What is Lennox-Gastaut Syndrome? ~
Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy characterized by treatment-resistant epilepsy of variable type, slow spike-wave or fast paroxysmal EEG patterns, and intellectual disability. Frequent seizures begin between ages 3 and 5. LGS occurs in 1-2 per 100,000 individuals.