Two Studies Provide Update on Effectiveness of Cannabidiol Derivative in Patients With Epilepsy

SEATTLE—Epidiolex, a purified and formulated form of cannabidiol, may be safe and effective for patients with epilepsy, according to one study, while another found that the drug affected serum concentrations of some concomitant antiepileptic drugs (AEDs), as will be reported at the 68th Annual Meeting of the American Epilepsy Society.

In one study, which explored initial efficacy and safety data, 23 patients (average age, 10) with treatment-resistant epilepsies, especially Dravet syndrome, were enrolled in two sites at New York University and the University of California, San Francisco. After researchers established a four-week baseline of frequency, type of seizures, and existing antiepileptic drug (AED) regimens, patients received a purified 98% oil-based cannabidiol extract, of known and constant composition at a dose of 5 mg/kg/day in addition to their baseline AED regimen.

The daily dose was gradually increased until intolerance occurred or a maximum dose of 25 mg/kg/day was achieved. After three months of therapy, 39% of patients had a greater than 50% reduction in seizures with a median reduction of 32%. Seizure freedom occurred in three of nine patients with Dravet syndrome and in one of 14 patients with other forms of epilepsy. Adverse effects were mostly mild or moderate and included somnolence, fatigue, AED level increases, decreased appetite, weight gain, diarrhea, increased appetite, and weight loss.

“These results are encouraging, especially since they involved a group of children and young adults with very treatment-resistant epilepsy,” said Orrin Devinsky, MD, Director of the New York University Langone Comprehensive Epilepsy Center and Professor of Neurology, Neurosurgery, and Psychiatry at the New York University School of Medicine. “However, we await the planned double-blind study to truly assess the safety and efficacy of Epidiolex [GW Pharmaceuticals; United Kingdom].”

The second study examined the drug interactions between existing AEDs and Epidiolex. In this study, 33 patients (average age, 10) were taking an average of three different AEDs, including clobazam (54.5% of patients), valproate (36.4%) and levetiracetam (30.3%), felbamate (21.2%), lamotrigine (18.2%), and zonisamide (18.2%). Baseline AED concentrations were established and then taken again after the addition of cannabidiol. Patients were given a purified 98% cannabidiol extract, of known and constant composition at a dose of 5 mg/kg/day in addition to their baseline AEDs.

In patients taking multiple AEDs, the addition of cannabidiol may be associated with changes in serum concentrations of some concomitant AEDs. A subset of patients experienced an increase in clobazam concentrations requiring a dose adjustment and suggesting cannabidiol’s effects on the major metabolic pathway of clobazam.

“These results support experimental findings that cannabidiol can affect metabolism of some common AEDs, though the effects may not be seen in all patients,” said Daniel Friedman, MD, an epileptologist and a clinical neurophysiologist at the New York University Langone Comprehensive Epilepsy Center. “More studies are needed to understand the potentially complex interactions between cannabidiol and other drugs, but in the meantime, frequent monitoring of drug levels is warranted in children taking cannabidiol-containing products, including medicinal cannabis.”

SEATTLE—Epidiolex, a purified and formulated form of cannabidiol, may be safe and effective for patients with epilepsy, according to one study, while another found that the drug affected serum concentrations of some concomitant antiepileptic drugs (AEDs), as will be reported at the 68th Annual Meeting of the American Epilepsy Society.

In one study, which explored initial efficacy and safety data, 23 patients (average age, 10) with treatment-resistant epilepsies, especially Dravet syndrome, were enrolled in two sites at New York University and the University of California, San Francisco. After researchers established a four-week baseline of frequency, type of seizures, and existing antiepileptic drug (AED) regimens, patients received a purified 98% oil-based cannabidiol extract, of known and constant composition at a dose of 5 mg/kg/day in addition to their baseline AED regimen.

The daily dose was gradually increased until intolerance occurred or a maximum dose of 25 mg/kg/day was achieved. After three months of therapy, 39% of patients had a greater than 50% reduction in seizures with a median reduction of 32%. Seizure freedom occurred in three of nine patients with Dravet syndrome and in one of 14 patients with other forms of epilepsy. Adverse effects were mostly mild or moderate and included somnolence, fatigue, AED level increases, decreased appetite, weight gain, diarrhea, increased appetite, and weight loss.

“These results are encouraging, especially since they involved a group of children and young adults with very treatment-resistant epilepsy,” said Orrin Devinsky, MD, Director of the New York University Langone Comprehensive Epilepsy Center and Professor of Neurology, Neurosurgery, and Psychiatry at the New York University School of Medicine. “However, we await the planned double-blind study to truly assess the safety and efficacy of Epidiolex [GW Pharmaceuticals; United Kingdom].”

The second study examined the drug interactions between existing AEDs and Epidiolex. In this study, 33 patients (average age, 10) were taking an average of three different AEDs, including clobazam (54.5% of patients), valproate (36.4%) and levetiracetam (30.3%), felbamate (21.2%), lamotrigine (18.2%), and zonisamide (18.2%). Baseline AED concentrations were established and then taken again after the addition of cannabidiol. Patients were given a purified 98% cannabidiol extract, of known and constant composition at a dose of 5 mg/kg/day in addition to their baseline AEDs.

In patients taking multiple AEDs, the addition of cannabidiol may be associated with changes in serum concentrations of some concomitant AEDs. A subset of patients experienced an increase in clobazam concentrations requiring a dose adjustment and suggesting cannabidiol’s effects on the major metabolic pathway of clobazam.

“These results support experimental findings that cannabidiol can affect metabolism of some common AEDs, though the effects may not be seen in all patients,” said Daniel Friedman, MD, an epileptologist and a clinical neurophysiologist at the New York University Langone Comprehensive Epilepsy Center. “More studies are needed to understand the potentially complex interactions between cannabidiol and other drugs, but in the meantime, frequent monitoring of drug levels is warranted in children taking cannabidiol-containing products, including medicinal cannabis.”

SEATTLE—Epidiolex, a purified and formulated form of cannabidiol, may be safe and effective for patients with epilepsy, according to one study, while another found that the drug affected serum concentrations of some concomitant antiepileptic drugs (AEDs), as will be reported at the 68th Annual Meeting of the American Epilepsy Society.

In one study, which explored initial efficacy and safety data, 23 patients (average age, 10) with treatment-resistant epilepsies, especially Dravet syndrome, were enrolled in two sites at New York University and the University of California, San Francisco. After researchers established a four-week baseline of frequency, type of seizures, and existing antiepileptic drug (AED) regimens, patients received a purified 98% oil-based cannabidiol extract, of known and constant composition at a dose of 5 mg/kg/day in addition to their baseline AED regimen.

The daily dose was gradually increased until intolerance occurred or a maximum dose of 25 mg/kg/day was achieved. After three months of therapy, 39% of patients had a greater than 50% reduction in seizures with a median reduction of 32%. Seizure freedom occurred in three of nine patients with Dravet syndrome and in one of 14 patients with other forms of epilepsy. Adverse effects were mostly mild or moderate and included somnolence, fatigue, AED level increases, decreased appetite, weight gain, diarrhea, increased appetite, and weight loss.

“These results are encouraging, especially since they involved a group of children and young adults with very treatment-resistant epilepsy,” said Orrin Devinsky, MD, Director of the New York University Langone Comprehensive Epilepsy Center and Professor of Neurology, Neurosurgery, and Psychiatry at the New York University School of Medicine. “However, we await the planned double-blind study to truly assess the safety and efficacy of Epidiolex [GW Pharmaceuticals; United Kingdom].”

The second study examined the drug interactions between existing AEDs and Epidiolex. In this study, 33 patients (average age, 10) were taking an average of three different AEDs, including clobazam (54.5% of patients), valproate (36.4%) and levetiracetam (30.3%), felbamate (21.2%), lamotrigine (18.2%), and zonisamide (18.2%). Baseline AED concentrations were established and then taken again after the addition of cannabidiol. Patients were given a purified 98% cannabidiol extract, of known and constant composition at a dose of 5 mg/kg/day in addition to their baseline AEDs.

In patients taking multiple AEDs, the addition of cannabidiol may be associated with changes in serum concentrations of some concomitant AEDs. A subset of patients experienced an increase in clobazam concentrations requiring a dose adjustment and suggesting cannabidiol’s effects on the major metabolic pathway of clobazam.

“These results support experimental findings that cannabidiol can affect metabolism of some common AEDs, though the effects may not be seen in all patients,” said Daniel Friedman, MD, an epileptologist and a clinical neurophysiologist at the New York University Langone Comprehensive Epilepsy Center. “More studies are needed to understand the potentially complex interactions between cannabidiol and other drugs, but in the meantime, frequent monitoring of drug levels is warranted in children taking cannabidiol-containing products, including medicinal cannabis.”