British researchers have determined that a little-studied chemical in the cannabis plant could lead to effective treatments for epilepsy, with few to no side effects.

The team at Britain’s University of Reading, working with GW Pharmaceuticals and Otsuka Pharmaceuticals, tested cannabidivarin, or CBDV, in rats and mice afflicted with six types of epilepsy and found it “strongly suppressed seizures” without causing the uncontrollable shaking and other side effects of existing anti-epilepsy drugs.

According to the findings, reported this week in the British Journal of Pharmacology, CBDV also delayed and reduced seizures when used in conjunction with two common anti-convulsant drugs.

“There is a pressing need for better treatments for epilepsy,” said Dr. Ben Whalley, the lead researcher.  “It’s a chronic condition with no cure and currently, in around one third of cases, the currently available treatments do not work, cause serious side-effects and increase fatalities.”

The study, he added, highlights “the potential for a solution based on cannabinoid science. It has shown that cannabidivarin is the most effective and best tolerated anticonvulsant plant cannabinoid investigated to date.”

The casual use of marijuana -- or cannabis -- to control seizures dates back to ancient times. Its most prominent component, THC, is among those shown in animal studies to have strong anti-convulsant properties, but its mind-altering effects have made it unsuitable for pharmaceutical development.

A number of the plant’s more than 100 cannabinoids are non-psychoactive, however. The most studied among them is cannabidiol, or CBD, which has shown promise for multiple sclerosis spacticity, nausea, epilepsy and schizophrenia. Animal studies with CBD have also shown it to be effective as a neuoroprotectant and cancer-fighting agent.

In recent years, California’s medical marijuana proponents have begun to breed plants for higher CBD content and develop customized tinctures for patients with a range of ailments. Those treatments  combine high doses of CBD with smaller amounts of THC.

Yet CBD’s widely known structure and well-studied uses mean that the pharmaceutical industry has less of an opportunity to protect patents on its use and profit from any drug development, said Whalley and Raphael Mechoulam, the Israeli researcher who first identified the structure of the compound nearly half a century ago and has conducted many key CBD studies.

CBDV is a closely related chemical compound. While it was discovered in 1969, the research made public this week was the first conducted in animals, said Whalley, and only two small in vitro studies have been published, neither of them related to epilepsy.

“The commercial protection can be good even if the compound itself was identified some time ago, as long as the proposed use is novel,” he said. “The better described the ‘new use’ is, the stronger the protection.”

Medical marijuana proponents largely dismiss pharmaceutical industry efforts as too profit-driven, and say that encourages researchers to find a “magic bullet” compound rather than work with the complex benefits that the whole plant provides. Yet Whalley countered that “to make a cannabis-based medicine available and accessible to a global patient community, the only viable route is via conventional drug development, which is dictated by governmental legislation [and] regulation.”

Dr. Stephen Wright, research and development director for GW Pharmaceuticals, which already markets a drug outside the U.S. that is half THC and half CBD for multiple sclerosis patients, said the company hoped to advance the CBDV research on epilepsy to human trials by next year.

Epilepsy affects about 1% of people worldwide, and is caused by excessive electrical activity in the brain, which leads to seizures that can be fatal.

Also

Researchers at the University of Reading have discovered that three compounds found in cannabis can help to reduce and control seizures in epilepsy.
Dr Ben Whalley, who is leading the research at the department of pharmacy at the University of Reading, said tests in animals had shown the compounds effective at preventing seizures and convulsions while also having less side effects than existing epilepsy drugs.
He said: “There was a stigma associated with cannabis that came out from the 60s and 70s associated with recreational use, so people have tended not to look at it medicinally as a result.
“Cannabis is thought of being a treasure trove of compounds that could be used for pharmacological development. We have a list of around a dozen potential candidates for epilepsy and have tested three that show promise.
“These compounds are very well tolerated and you are not seeing the same kind of side effects that you get with the existing treatments.”

Epilepsy is caused by sudden bursts of electrical activity in the brain that disrupt the normal way in which messages are transmitted. This can cause debilitating seizures and fits that can lead to sufferers injuring themselves.
Dr Whalley, together with his colleagues Dr Claire Williams and Dr Gary Stephens have been working with drug company GW Pharmaceuticals to develop and test new treatments for the disease from cannabis.
Two of the compounds they have identified, one called cannabidiol and the other called GWP42006, have been highly effective at controlling seizures in animals and the researchers now hope to begin clinical trials in humans within the next three years. Neither of the compounds produce the characteristic “high” associated with cannabis use.
The scientists, whose latest findings on the compounds are published in the scientific journal Seizure, believe they work by interfering with the signals that cause the brain to become hyper-excitable, which leads to epileptic seizures.

Until now the main medicinal use that has been explored for cannabis has been in treating Multiple Sclerosis and for pain relief in cancer patients.
Mark Rogerson, from GW Pharmaceuticals, said: “Medicinal cannabinoids can treat a wide range of diseases like MS and pain.
“The work by Dr. Whalley and his team is taking us into a whole new area where there is a real unmet need. The stigma is counterbalanced by the fact that it is a serious medicine for a serious condition.”
A spokesman for Epilepsy Action said: “Epilepsy is a condition that can be very difficult to treat. We are aware of some people with epilepsy who have used cannabis for medicinal purposes. However, it should be noted that although taking cannabis may reduce seizures in some people, it could actually increase seizures in others.
“We therefore welcome research into this treatment area. It could help our understanding of alternative therapies and may prove useful in the long-term for people whose epilepsy does not respond to more traditional methods.”