Marijuana drug at GRU works differently

Georgia Regents Uni­ver­sity and the state of Georgia have worked for months to land a marijuana-derived drug clinical trial for children with difficult seizure disorders. How the drug actually works to limit seizures is still being worked out.

Gov. Nathan Deal announced last week that GRU and other sites in Georgia would host clinical drug trials for Epidiolex, a drug made by GW Pharmaceuticals of London. The company’s chairman and founder, Dr. Geoffrey W. Guy, visited GRU last week to talk about GW’s research into Epidiolex, which is a purified version of cannabidiol oil.

Cannabidiol, or CBD, is one of about 70 active ingredients that have been isolated from the cannabis sativa plant that the company has specially bred to produce high levels of the plant chemical and to eliminate the other well-known marijuana chemical, tetrahydrocannabinol or THC. That is the psychoactive part of the plant that produces the “high” from smoking marijuana; CBD actually blocks its effects.

Both THC and CBD are anticonvulsants, but THC interferes with brain development in children, which is why the company worked for 10 years to breed THC out of its plants, Guy said.

Where THC appears to activate certain receptors on cells in the brain, CBD blocks those receptors, said Dr. Jimok Kim, an assistant professor in GRU’s Department of Neuroscience and Regenerative Medicine.

CBD is a powerful anti-inflammatory and appears to tamp down the excitability of neurons and decrease the duration of epilepsy seizures, Guy said.

Exactly how this happens is unknown, Kim said.

“Both clinical studies and also basic research are being done, but the exact mechanisms of anti-epilepsy (effect) is not quite known yet,” he said.

CBD appears to stimulate a natural system called the endocannbinoid system that appears to help govern the excitability of neurons, Guy said. CBD appears to be able to prolong the duration of the cannabinoids the body produces, which are normally degraded quickly, Kim said,

One way it affects these neurons might be through the traffic of calcium in and out of the cell. Calcium can induce neurotransmitter release and increases the excitability of neurons, and CBD can block up calcium channels into those cells, Kim said.

“Because CBD blocks calcium channels, it could be one of the mechanisms of anti-epilepsy (effect) of CBD,” he said.

And it does it very well, Guy said.

“Cannabidiol is probably one of the most potent modulators of intracellular calcium,” he said. CBD also seems to avoid the motor and behavioral impairment that accompany many current epilepsy drugs, Guy said.

“That’s why people think CBD is promising because CBD has no psychoactive side effects,” Kim said.

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