Pubdate: Sun, 20 May 2001 Source: Sacramento Bee (CA) Copyright: 2001 The Sacramento Bee Contact: http://www.sacbee.com/ Details: http://www.mapinc.org/media/376 Author: Edie Lau, Bee Science Writer Bookmark: http://www.mapinc.org/mmj.htm (Medical Marijuana) Bookmark: http://www.mapinc.org/kubby.htm (Kubby, Steve) POT'S VALUE AS MEDICINE STILL HAZY People hearing Jody Corey-Bloom's plan to study how smoking marijuana affects patients stiffened by multiple sclerosis often can't resist teasing the doctor. "Oh, nice research to be in," they say with a mischievous smile. At the same time, many are curious about the possible medicinal value of the plant called cannabis sativa. Because for all the stories about how marijuana cures ills, rigorous scientific studies of its therapeutic effects are scarce. The absence of ample data is due largely to the difficulty of legally obtaining marijuana for medical research. The federal government for 20 years has grown cannabis to research the drug's potential for abuse and addiction; it was not until 1999 that it established a policy for making marijuana available to independent researchers interested in testing for medicinal effects. "The research has not been easy to do," said Dr. Donald Abrams, director of the AIDS program at San Francisco General Hospital. "I mean, you're dealing with a controlled substance that has a lot of emotional overlay. There are a lot of regulatory issues." Those regulatory issues have made for a Catch-22: The federal Controlled Substances Act does not recognize a medical benefit to marijuana, and its status under that law as a "Schedule I" controlled substance makes it difficult to obtain for medical research. The conundrum was highlighted last week in a U.S. Supreme Court ruling that the Oakland Cannabis Buyers' Cooperative, in distributing marijuana for medical use, was not exempt from prosecution under federal drug laws. "It is clear from the text of the Act that Congress determined that marijuana has no medical benefits worthy of an exception granted to other drugs," Justice Clarence Thomas wrote for the unanimous court. The one legal use of the drug, the court noted, is for government-approved research projects. But getting that approval is extremely complicated. Abrams tried and failed for five years to obtain marijuana legally before gaining the support of the National Institute on Drug Abuse, which is in charge of the federally grown crop. After rewriting his proposal a third time, Abrams in 1997 received from NIDA $1 million and the marijuana necessary to compare the safety for AIDS patients of smoking pot vs. ingesting Marinol, a capsule form of THC, the foremost psychoactive ingredient in marijuana. Some AIDS patients smoke the drug to stimulate appetite and help them maintain their weight. That was the first study to be done with human HIV patients and smoked marijuana. Abrams said he found that neither the cigarettes nor Marinol appeared to further degrade the immune system. Moreover, the patients ate more and gained weight with both forms of the drug. Abrams is set now to begin another cannabis study, this one focused on whether the drug would alleviate nerve pain in AIDS patients. This time, Abrams need not worry about the logistics of obtaining marijuana because someone else is doing it on his behalf. Abrams, Corey-Bloom and two other scientists are the first to have research proposals approved by the new California Center for Medicinal Cannabis Research. Unique in this country, the center was established by a 1999 state law with $3 million in funding. The first batch of studies still are awaiting the final go-ahead. The research center had to submit the proposals for review and approval by a state research advisory panel, a scientific review committee at the U.S. Department of Health and Human Services, the National Institute on Drug Abuse, the U.S. Food and Drug Administration, and the federal Drug Enforcement Administration. Once a DEA license is secured, said center co-director Drew Mattison, the center will place an order for marijuana with NIDA, which grows pot on one acre of land near the University of Mississippi. All the sites where the marijuana will be used must be inspected by NIDA. The process "is very, very complex," Mattison said. "It has been very, very detail-oriented, and also new territory for some of these regulatory agencies. You have to kind of develop policy as they go along." Exploring the therapeutic effects of nicotine is much easier, even though, according to addiction expert Avram Goldstein of Stanford University, nicotine is far more addictive than marijuana. Goldstein said advocates of legalizing marijuana share responsibility for impeding scientific research. "I have been involved in looking at some of those proposed studies, and there's just an awful lot of junk science there (from) people who have a bias in favor of smoking marijuana," he said. Much of the impetus for research has come from patients and the public. In 1996, a majority of California voters approved the use of marijuana as an alternative treatment for certain medical conditions. For years, doctors had been hearing from seriously ill patients how smoking marijuana provided relief where other medications failed. One such patient was Steve Kubby. A former Libertarian candidate for governor, Kubby and his wife, Michele, were prosecuted last year in Placer County for growing marijuana in their home. Kubby has a rare form of adrenal cancer that typically kills. But he has survived seemingly miraculously for more than 16 years, and his physician, Dr. Vincent DeQuattro of the University of Southern California, testified that marijuana appeared to be the reason. DeQuattro, who was traveling last week, this week, said in an interview by e-mail that Kubby turned to marijuana after the conventional medications DeQuattro prescribed made him sick. "I did testify that since he could not take conventional medications, I approved of his continuing that therapy," DeQuattro said. "He has harbored this tumor with equanimity for ... years. The marijuana-related counts against the Kubbys ultimately were dismissed. Spurred by medical marijuana laws in several states, the National Institutes of Health in 1997 appointed an expert panel to review the scientific literature on marijuana as therapy. The panel concluded from the information -- much of it anecdotal or based on animal studies -- that evidence was compelling enough to merit further research in five areas: appetite stimulation; nausea and vomiting associated with cancer treatment; neurological and movement disorders; pain; and glaucoma. That report helped prompt NIDA to make its pot available to independent researchers. One area in which considerable data exists on humans is in the use of cannabis to ease nausea. However, the panel observed, most of the clinical trials used dronabinol (the generic name for Marinol), the THC capsule approved in the mid-1980s for use by cancer patients on chemotherapy. The problem with dronabinol is that its effects don't necessarily follow those of smoked marijuana. The plant contains more than 400 chemicals, about 60 of which are psychoactive ingredients called cannabinoids. THC is only one, albeit the most abundant. THC capsules also take hours to work, whereas smoked marijuana has effects within minutes. Moreover, experienced smokers are able to regulate their doses by controlling their "puff rate" and the depth of their breath -- possibly delivering enough drug to ease their symptoms without becoming dysfunctionally "high." At the same time, smoking carries its own risks, including irritation of the respiratory system. Mattison, co-director of the California cannabis research center, said the center is working with a pharmaceutical company to develop an under-the-tongue spray. Researchers elsewhere are trying to develop inhalers and a skin patch. The flowering tops and leaves of the hearty weed cannabis sativa seem to have been as medicine for centuries. In 1993, researcher Raphael Mechoulam of Hebrew University in Jerusalem reported recovering tiny amounts of THC from a 1,600-year-old family tomb, near the corpse of a young woman who evidently died in childbirth. It was Mechoulam who in 1964 isolated THC from marijuana, spurring the interest of scientists around the world on cannabinoids, which are found in no other plant. Today, researchers know of two natural cannabinoids in the human body, and have identified cannabinoid receptors in the brain and immune system. Their function is, at this point, unclear. Growing understanding of the role of natural cannabinoids will be critical to understanding marijuana's effects on the body, for better and for worse. But to fully exploit the beneficial effects the plant may confer will require experiments using the drug and human subjects. Aside from the difficulty in obtaining legal marijuana, said Corey-Bloom, it's tough designing a bullet-proof study. "If somebody's not blinded (to whether they're receiving the drug or a placebo), then I think that it's very easy for them to report that (their condition) is improved in one situation and not in another," said Corey-Bloom, who directs the multiple sclerosis clinic at the University of California, San Diego, and proposes to study marijuana and spasticity, or stiffness. "I think it's important to separate out the euphoria from real medicinal benefits. We're not necessarily against someone feeling good who has a chronic illness," she added, "but I think it's important to say it didn't have an effect on spasticity, but in fact they felt better." When the Supreme Court decision on medical marijuana came out last week, Corey-Bloom paid close attention, and found she basically agreed. "We need to get some good data," she said. "I thought it really suggested that our work was more timely than ever." - --- MAP posted-by: Josh Sutcliffe