A clinical trial by GW Pharma studied children and adults age 2-55 with Lennox-Gastaut syndrome (LGS). This is a childhood onset medically refractory epilepsy characterized by multiple seizure types and evidence of brain damage. The study reported “drop seizures” defined as an atonic, tonic, or tonic-clonic seizure involving the entire body, trunk, or head that led (or could have led) to a fall, injury, slumping in a chair, or hitting the patient’s head on a surface. All patients demonstrated slow spike wave (3 Hz.) on EEG. Cannabidioil (CBD) in a 100 mg / ml oral solution was administered twice daily to 72 patients compared to 84 controls, escalating from 2.5 mg / Kg / day to 20 mg / Kg / day over 2 weeks. This was added on to their current therapy: treated patients took between 1-5 antiepileptic drugs (AEDs), median of 3, with 94% of the treatment group taking multiple AEDs. This 2 week titration period was followed by a 12 week maintenance period. The authors reported a 44% median reduction in drop seizures v 14% in placebo during the ? week treatment period, and 49% with CBD vs 20% in control during the maintenance period. IN addition, 44.2% of the CBD group experienced 50% reduction in seizure frequency during treatment, versus 23% on placebo. In one placebo and 20 CBD patients there was an increase in liver enzymes (AST or ALT) 3x the upper limit of normal, none with associated liver failure (significant increase in bilirubin). Sixteen patients were on concomitant valproic acid but it is not clear if these 16 had increased liver function tests. This is one of the first clinical trials that establishes the efficacy or ability of CBD to decrease seizure frequency in patients with LGS. The trial was conducted in a way that tries to eliminate patient and caregiver bias: neither the patients or the researchers knew who was getting drug or placebo. It was conducted in several different clinical sites. No significant adverse events were reported, though the increase in liver function tests suggests that CBD may affect the liver. Alternatively it may indicate that CBD interacts with one of the other AEDs, or that it may simply, either by itself, or though an interaction with other AEDs affect the metabolism of drugs in the liver. The exact cause of the elevated liver function tests is unknown. The authors did not disclose what other drugs the patients with elevated LFTs were taking. Many AEDs cause in an increase in liver function tests in the absence of overt liver disease. Nonetheless, until further studied, patients on CBD should watch out for liver disease and physicians should be aware. The paper also suggests that up to 20 mg / Kg of CBD in oral solution is well tolerated. The data on seizure reduction suggests that on average patients noted a 29% reduction in seizures over in above what the placebo patients experienced. It is not clear why placebo patients had such a large reduction in seizure frequency, but this is common in AED trials.
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