Pubdate: Thu, 22 Aug 2002 Source: Worcester Telegram & Gazette (MA) Copyright: 2002 Worcester Telegram & Gazette Contact: http://www.telegram.com/ Details: http://www.mapinc.org/media/509 Note: only publishes letters from state residents. Author: Lisa Eckelbecker Bookmark: http://www.mapinc.org/pot.htm (Cannabis) CANNABIS MAY FIGHT ARTHRITIS BOSTON-- A synthetic compound developed from an ingredient in marijuana could be useful in treating rheumatoid arthritis without generating the buzz of marijuana, according to findings presented yesterday by a University of Massachusetts Medical School professor. Sumner H. Burstein said his laboratory's studies indicate that the compound - -- ajulemic acid -- can thwart one of the body's chemicals that contributes to the destructiveness of rheumatoid arthritis. In addition, studies in mice show that the compound can protect joints from damage, and a small study in humans has suggested the drug is safe, Mr. Burstein said. "We believe that (the compound) will replace aspirin and similar drugs in most applications primarily because of a lack of toxic side effect," Mr. Burstein said. Mr. Burstein presented his findings yesterday at the American Chemical Society's annual meeting. His results were reported during a poster session, in which scientific teams display charts, graphs, photos and condensed descriptions of their work. Among the authors of Mr. Burstein's poster was Dr. Robert B. Zurier, a professor of medicine, cell biology and pathology at UMass who has collaborated with Mr. Burstein on ajulemic acid. Ajulemic acid is a synthetic compound that Mr. Burstein developed and then patented in 1992. He named it by putting together the first letters of the names of his grandchildren: Adam, Julia and Emily. Atlantic Technology Ventures Inc. of New York licensed the compound, also known as CT-3, in the mid-1990s. It commissioned animal studies and human studies that suggested the drug was safe and had no mood- altering effects. Then last month, Indevus Pharmaceuticals Inc. of Lexington licensed exclusive worldwide rights to the compound from Atlantic Technology Ventures. Indevus is backing a study of the compound in 21 chronic pain patients in Germany. "The reason our guys liked it so much is it seems to have a lot of activity without the psychotropic effects you get with other drugs," said William B. Boni, Indevus vice president of corporate communications. Those "effects," of course, are the infamous marijuana high. And the fact that marijuana is illegal has made it one of the most controversial sources of medical research. Even as states have passed medical marijuana laws, the U.S. Supreme Court has affirmed federal law that declares marijuana a substance with no medical benefits. Some researchers studying marijuana, or cannabis, have reported difficulty in getting federal grants or purchases of cannabis from the government for their studies. Mr. Burstein said that has not been the case with his research, which has been going on for more than 30 years with government support. "In the beginning, the thrust was to answer the question, 'Is it harmful?' " he said. "In the '70s, all the people in the field were working to resolve those issues ... It's certainly safer than alcohol, nicotine. But the political issue was not settled at all. It's a very emotional issue." Another problem is that the one marijuana-derived drug on the market, Marinol, has been criticized because some patients taking it experience the mood-altering effects of marijuana. Ajulemic acid is different, however, because it is a synthetic compound that Mr. Burstein developed from a metabolite of tetrahydrocannabinol, or THC, the main ingredient in marijuana that produces a high. Metabolites are substances that the body produces as it processes a drug. In the research he reported yesterday, Mr. Burstein said he and his collaborators started with blood and joint cells from healthy people and patients with inflammatory arthritis. Rheumatoid arthritis occurs when the body comes under attack from its own powerful immune system. The researchers added ajulemic acid to the cell samples, then exposed them to a toxin that produces inflammation. The researchers found that ajulemic acid reduced the cells' secretion of interleukin 1-beta, a substance produced by the body and associated with joint destruction in rheumatoid arthritis. The compound had no effect on the cells' production of tumor necrosis factor, another substance produced by the body and considered a key player in rheumatoid arthritis. Mr. Burstein said the findings supported earlier studies in rats, which showed that ajulemic acid protected the animals from joint destruction, although not from inflammation. "Almost 80 percent of the animals were spared from bone destruction, even though there was evidence the joints had become inflamed," he said. Mr. Burstein said ajulemic acid also appears to inhibit the body's production of other potentially harmful substances: T cells, which are part of the immune system, and the COX-2 enzyme, which is the target of the popular osteoarthritis drug Celebrex. The way the drug acts remains unknown and is a subject that Mr. Burstein said he hopes to continue studying. He is seeking additional federal grant money to support the work. If it proves safe and effective in humans, researchers could find additional applications for ajulemic acid. Atlantic Ventures reported earlier this year that British researchers observed that the drug reduced spasticity in animals with the symptoms of multiple sclerosis. The findings are encouraging for researchers who have had to fend off skeptics of cannabis research for years, Mr. Burstein said. "It's become a legitimate area of science," Mr. Burstein said. "For years we were considered outsiders, outside the mainstream of biological science." - --- MAP posted-by: Terry Liittschwager