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ISRAEL: Israeli researcher develops cannabis compound that stops
David Brinn Israel21C
Sunday 12 Jun 2005 Whether or not the potential medical benefits of marijuana outweigh the dangers is a long-debated issue and currently a political hot potato. A recent Israeli breakthrough adds a new twist: a 25-year old Hebrew University doctoral student has developed a derivative of the cannabis plant which has been shown to be effective in arresting cancerous growths in laboratory and animal tests. Natalya Kogan - working under the supervision of noted cannabis researcher Prof. Raphael Mechoulam of the university's School of Pharmacy, was last week awarded a Kaye Innovation Award for her work, an annual award for innovative research established in 1994 Kogan's accomplishment involved developing new compounds - known as quinonoid cannabinoids - that her research has shown to parallel in their activity a group of anti-cancer drugs, the best known of which is daunomycin. "Quinonoid cannabinoids are derived from hashish - but when they go through an oxidation process, they takes on the chemical structure of anti-cancer drugs like daunomycin," Kogan told ISRAEL21c. However, while daunomycin is toxic to the heart, Kogan, with Dr. Ronen Beeri and Dr. Gergana Marincheva of Hadassah University Hospital, Ein Kerem, found that the quinonoid cannabinoids are much less cardiotoxic. The combination of the development of quinonoid compounds that display anticancer activity, but are less toxic, is a major therapeutic accomplishment, according the Kaye Prize board. All of the compounds synthesized by Kogan inhibited cancer cell growth in cell culture, and one of them was found to markedly reduce the volume of tumors in studies on mice. The cannabinoid quinones were found to act through a rather unique pathway of cancer cell destruction - by specific inhibition of topoisomerase II, an enzyme that participates in cell replication. "We synthesized the compound, and went into the lab to research what it does to cancer cells and discovered it was able to kill cancer cells in vitro," said Kogan. "We then injected cancer cells into mice, they were administered the cannabinoids. We measured the tumor diameters and found that they were half as big as the tumors in the mice in the control group." Additionally, the most active compound in the series developed by Kogan, as well as some other cannabinoids, were found by Kogan and Prof. Ruth Galilli of the Hebrew University to have anti-angiogenic properties. Angiogenesis, the process of new blood vessel formation, is crucial for tumor growth, and much effort has been invested by researchers in the development of compounds with anti-angiogenic activity. "Basically, we found that our compound attacked tumors from two directions. It can kill cancer cells themselves - by inhibiting tan enzyme that participates in cell replication. And from the other sides, we saw that the compound arrested blood cell formation. When someone has a tumor, it needs an oxygen supply and nutrients to grow - with out it, the tumor won't develop by itself. The compound was able to inhibit these angiogenic properties," said Kogan. According to Kogan, the fact that the compounds have anti-cancer properties and are more selective and potent than standard chemotherapy drugs, increases their potential for use in new anti-cancer drugs. Her research was conducted in collaboration with Prof. Michael Schlesinger at the Hebrew University-Hadassah Medical School and Prof. Ester Priel at Ben-Gurion University of the Negev. Born in the Ukraine, Kogan immigrated to Israel in 1995 with her parents, and earned B.Pharm and M.Sc degrees at the HU School of Pharmacy, graduating with excellence. "I've been interested in cancer research for many years. I've actually been sitting in the same school of pharmacy for nine years now," she said with a laugh. "My goal was to develop new drugs, and working as a lab technician for Prof. Mechoulam, I got interested in cannabinoids." Mechoulam was one of the first researchers to discover the medical potential of cannabis. Cannabis-derived molecules are already used to prevent nausea from chemotherapy, improve the appetite of AIDS patients, alleviate anxiety, and treat sleepwalking. "Almost every pharmaceutical in the world uses the active ingredients in cannabis as a basis for existing drugs and those under development," Mechoulam told Globes. Mechoulam's research was behind the development of the drug Dexanabinol developed by Israeli company Pharmos for the treatment of head trauma was based on Mechoulam's research. In clinical trials last year, however, Dexanabinol was ultimately found ineffective in treating humans. "Pharmos has rights to two ingredients developed at our lab: Dexanabinol (H-211), and an anti-inflammatory (H-208). Dexanabinol is not a bad drug at all, but it's hard to conduct clinical trials for it. In order to function properly, it has to be delivered within minutes of an injury. But to conduct a clinical trial you have to get the patient's permission, or in the case of head trauma, from his or her family. This requires several hours, and by this time the drug apparently cannot stop the damage. "Pharmos is continuing to test Dexanabinol to prevent cognitive damage following heart surgery. In this case, you can ask the patient before surgery whether he wants to participate in the clinical trial," he said. Kogan, meanwhile, is continuing research on her quinonoid cannabinoids, and said that winning the Kaye prize has been a blessing for her. "It's great, I'm really pleased. And maybe now people will learn about what we're doing and be interested in investing in the research." Kogan's prize comes amid the backdrop of the Supreme Court decision last week allows for terminally ill patients who smoke marijuana to alleviate pain to be prosecuted for violating federal drug laws, even if their own state laws allow them to use marijuana for medical purposes. She told ISRAEL21c that potential drugs based on her research would not fall in the same category. "I think patients should be allowed to use marijuana derivatives. My components are not psychotropic- you won't get high from them. And if they help, I don't see a reason why they shouldn't be legal." http://www.israel21c.org/
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