Cannabis, cannabidiol, and epilepsy — From receptors to clinical response

Recreational cannabis use in adults with epilepsy is widespread. The use of cannabis for medicinal purposes is also becoming more prevalent. For this purpose, various preparations of cannabis of varying strengths and content are being used. The recent changes in the legal environment have improved the availability of products with high cannabidiol (CBD) and low tetrahydrocannabinol (THC) concentrations. There is some anecdotal evidence of their potential efficacy, but the mechanisms of such action are not entirely clear. Some suspect an existence of synergy or “entourage effect” between CBD and THC. There is strong evidence that THC acts via the cannabinoid receptor CB1. The mechanism of action of CBD is less clear but is likely polypharmacological. The scientific data support the role of the endocannabinoid system in seizure generation, maintenance, and control in animal models of epilepsy. There are clear data for the negative effects of cannabis on the developing and mature brain though these effects appear to be relatively mild in most cases. Further data from well-designed studies are needed regarding short- and long-term efficacy and side effects of CBD or high-CBD/low-THC products for the treatment of seizures and epilepsy in children and adults.

Highlights

  • Cannabidiol (CBD) and tetrahydrocannabinol (THC) act via different mechanisms.
  • THC acts via the endocannabinoid CB1 receptor.
  • CBD appears to act synergistically with THC, but the mechanism is not clear.
  • There are anecdotal data in support of cannabis efficacy for seizure control.
  • Chronic cannabis use produces long-term cognitive and constitutional effects.
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Low Dose of CBD Liquid Eases Epilepsy Seizures

Patients taking a 10-milligram (mg) daily dose of pharmaceutical grade cannabidiol (CBD) experienced nearly as great a reduction in seizures as patients on 20 mg, and with fewer side effects, said lead researcher Dr. Orrin Devinsky. He is director of NYU Langone’s Comprehensive Epilepsy Center in New York City.

This is the third clinical trial to show that the cannabidiol medication Epidiolex is useful in treating two rare forms of epilepsy, Lennox-Gastaut syndrome and Dravet syndrome, Devinsky said.

An advisory panel for the U.S. Food and Drug Administration unanimously recommended in April that Epidiolex be approved for use in the United States. The FDA does not have to follow the recommendations of its advisory panels, but it typically does.

Epidiolex is manufactured by the British firm GW Pharmaceuticals, which funded the latest clinical trial.

“This is a historic moment in medicine,” Devinsky said. “Hopefully, the FDA will approve this medication in their June meeting and cannabidiol will be available for children and adults with these two rare epilepsies.”

Although CBD oil has become a trendy cure-all, treatment of epilepsy is the only use that has garnered significant scientific evidence supporting its usefulness.

This latest study is the first to compare two different doses of Epidiolex head-to-head and against an inactive placebo, Devinsky said.

A total of 225 patients suffering from Lennox-Gastaut syndrome were divided into three groups. Those taking 20 mg of Epidiolex a day had 42 percent fewer seizures, on average, compared with 37 percent fewer seizures in the group taking 10 mg of the drug, and a 17 percent reduction in the placebo group.

But while the 20-mg dose was slightly more effective, it was not the first choice of parents, Devinsky said.

“When parents were asked to rate how their children did best, they actually had a slight preference for the 10-mg dose without knowing what it was,” he added.

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