Add-on CBD Reduces Seizures in Patients With Tuberous Sclerosis, Study Finds
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A Phase 3 clinical trial from GW Pharmaceuticals has found that Epidiolex, an oral CBD formulation, can effectively reduce the number of seizures in patients with tuberous sclerosis complex (TSC) by around 50 percent, compared to baseline levels.
Newly published in JAMA Neurology, the results show the effectiveness of add-on CBD up to a dosage of 50 milligrams per kilogram per day (mg/kg/day). The drug’s safety profile was judged to be similar to other CBD treatments used to control seizures in Dravet syndrome and Lennox-Gastaut syndrome.
In a statement, GW Pharmaceuticals confirmed that this work formed the basis of the US Food and Drug Administration’s (FDA) recent decision to approve Epidiolex for use in treating TSC-related seizures.
What is TSC?
Tuberous sclerosis complex is a rare genetic disease affecting the TSC1 and/or TSC2 genes, causing non-cancerous tumors to grow in the brain and other vital organs. These tumors can cause patients to experience various neurological problems, developmental delay, skin abnormalities, and diseases of the lung and kidneys.
In around 80-to-90 percent of TSC patients, these tumors also result in epileptic seizures, which, for the most part, cannot be controlled using traditional anticonvulsant medications.
Given the successes of other CBD seizure treatments in past trials, there was cause to investigate whether patients with TSC might find similar relief from CBD, in addition to their normal course of prescribed anti-epileptic medications.
“People living with TSC may experience focal seizures and spasms as infants and continue to suffer from seizures throughout their lifetime,” lead investigator Elizabeth Thiele, a professor of neurology at Harvard Medical School, said in a statement. Thiele is also the director of pediatric epilepsy and director of The Carol and James Herscot Center for Tuberous Sclerosis Complex at Massachusetts General Hospital.
“This study demonstrated that for patients with TSC and a high baseline burden of treatment-resistant, primarily focal, seizures, Epidiolex significantly reduced the frequency of seizures compared with placebo.”
The effects of add-on CBD treatment
Conducted at numerous sites across Australia, Europe, and the United States, the trial monitored the health of over 200 patients with TSC and epilepsy. Patients would receive either a placebo, a moderate 25 mg/kg/day dose of Epidiolex, or a higher dose of 50 mg/kg/day, on top of their normal treatment regimen and report back their seizure frequency and any adverse effects on a daily basis. Participants and their caregivers were also asked to give their own opinions on how effective they felt the treatments had been in improving their overall condition.
After four weeks of observation to establish baseline levels, patients were given increasing doses of CBD for a further four weeks. Once their dosage reached their prescribed level, the participants’ medication remained unaltered for a 12-week maintenance period.
Compared to recorded baseline levels, the number of reported seizures fell by around 48 percent in both of the groups given CBD. Those in the placebo group also reported a fall in seizure frequency. The researchers put this decrease down to “enhanced expectations for cannabidiol treatment.” Still, relative to the placebo group, seizure frequency was reduced by around 30 percent across the study period in those taking CBD.
Given the known drug interactions between the anticonvulsant medication clobazam and CBD, the scientists also investigated whether this effect might be contributing to the results seen. They found that over 70 percent of the participants were not taking clobazam, and yet these patients’ outcomes were still better than those seen in the placebo group – a finding that supports the efficacy of CBD in controlling seizures independent of clobazam use.
Cautions for higher dosages
While the safety profile of the add-on CBD was roughly equivalent to that seen in other epilepsy trials, roughly half of those originally allocated to receive the 50 mg/kg/day dosage were unable to reach or maintain that dosage for the length of the trial due to a range of different adverse events.
Most commonly, those patients who reduced their dosage or withdrew from the trial did so after developing a rash or itching, but others also reported drowsiness. Several patients also presented elevated levels of transient liver enzymes. These participants discontinued their treatment in order to avoid the possibility of liver injury.
Overall, based on the events reported, the researchers believe add-on CBD to have a broadly acceptable safety profile, though longer-term studies are to be pursued in a continuing open-label extension trial. As no great differences were seen in seizure control between the 25 and 50 mg/kg/day groups, the researchers recommend clinicians use the lower of the two doses in practice. This advice is incidentally in line with the current FDA-recommended maintenance dose.
“The publication of these results in JAMA Neurology reinforces the importance of Epidiolex as a new treatment option for people experiencing treatment-resistant seizures associated with TSC,” said Justin Gover, chief executive officer at GW Pharmaceuticals, in a statement. “We hope that the data will help clinicians to better understand the potential of Epidiolex to reduce focal and generalized seizure frequency in their patients with this condition.”