long, but interesting article... By Edie Lau -- Bee Science Writer Published 3:15 a.m. PDT Sunday, April 7, 2002 SAN FRANCISCO -- Robert has taken a lot of prescription drugs over the past 15 years. One made him vomit without warning. Another tasted like motor oil. One drove his cholesterol to heart-attack levels. Still another caused a hot, tingling pain in his hands and feet. Late last month, Robert checked into San Francisco General Hospital to test a drug to quiet the nerve pain. This one left him temporarily giggling and bewildered. As someone who's been sick from HIV for most of his adult life, Robert found the side effects of this test drug gentle. "It is really mild compared to everything else," he said. Another important difference between the test drug and other medications he's taken is that the test drug is illegal: It's marijuana. Under the circumstances, Robert is breaking ground, not breaking the law. He is the first participant in the first study to be encouraged and paid for by the state of California on the therapeutic effects of Cannabis sativa -- better known as pot. The study, led by Dr. Donald Abrams at the University of California, San Francisco, is under the aegis of the Center for Medicinal Cannabis Research. Unique in the country, the agency was established by a 1999 state law that provides $3 million a year for three years to research marijuana's potential as medicine. Three years earlier, in 1996, voters passed Proposition 215, allowing ill people to smoke marijuana under a physician's care. Research supported by the center is meant to help guide doctors on the appropriate uses and doses for specific ailments. Anecdotes abound on the therapeutic effects of cannabis, but most credible studies have been on laboratory animals. Further, past research largely focused on marijuana's health consequences, not potential benefits. With California in the vanguard, that's changing. Canada last year legalized the use of cannabis as medicine and is funding research on its healthful effects. Great Britain is considering allowing medical marijuana use, and supporting research. Social acceptance of marijuana as medicine is so new and tenuous that people involved in the research are cautious about their participation. Robert, for example, asked to withhold his last name in print. Apart from the UCSF study, the 39-year-old has a Proposition 215 permit to smoke marijuana for his nerve pain, which he's done at a cannabis club on weekends. Despite the fact that his smoking is legal, and that he lives in liberal San Francisco, Robert said using pot therapeutically is "kind of a closet-y thing." "It's a little tricky," he said, mindful of his Catholic upbringing. "I don't even know how I'm going to tell my parents." Hector Vizoso, a nurse experienced in clinical trials, hesitated before accepting a job at UCSF as study coordinator. "Because I'd be dispensing marijuana, would I be considered a dealer?" he wondered. His worries were calmed by Abrams, a 51-year-old physician, and staff members at San Francisco General, who knew what a medical cannabis study entails. In 1998, they undertook the first-ever study to be done on the use of smoked marijuana in people with HIV. The project followed a tenacious fight by Abrams for approval from the National Institute on Drug Abuse, keeper of the country's only legal source of research marijuana. Twice, his study proposals were rejected. On the third attempt, Abrams rephrased the research question, playing up the drug's possible faults: Might marijuana interfere with the medications used to counteract AIDS? Abrams won nearly $1 million in funding and a supply of marijuana to answer the question.\ >He found that marijuana didn't worsen AIDS virus levels. In fact, it helped patients eat more and gain weight. Abrams has cared for people with AIDS since before the disease had a name. He knew that some smoked marijuana on their own to quell nausea and stimulate their appetites. "We feel indebted and obligated to our patients to determine if it's safe and if it has some effect," he said. Abrams' new, three-year, $956,000 state-funded study focuses on the potential of cannabis to relieve AIDS-related peripheral nerve pain -- a debilitating pain in hands and feet that may occur as a result of the disease itself, or as a side effect of drugs taken for AIDS. One requirement of study participants is that they be experienced marijuana smokers. "We want to know people know how to inhale -- and know ... what it's like to be stoned, so they don't freak out and sue us," Abrams said. The study is starting as a pilot with 16 volunteers, most of whom still are being lined up. Each will stay in the hospital for nine days, smoking marijuana on seven of those days. Those who stick with the study for the full duration -- a commitment of about a month or so per person, including keeping a pain diary for a week before and a week after the hospital stay - are reimbursed $600 apiece. If all goes well with the pilot, a bigger study involving up to 100 subjects will follow. That study will use placebos -- marijuana cigarettes missing the chief active ingredient, THC -- and be double-blinded, meaning neither subjects nor researchers in contact with the subjects will know who gets the placebo and who gets the real thing. Robert was the first subject. He checked into the hospital March 27, bringing a stationary bicycle, music, books, props for meditating and a cooperative attitude. He was careful to smoke each marijuana cigarette exactly as directed: Inhale five seconds, hold 10 seconds, exhale, and pause for 45 seconds. Repeat. The first time, Robert wasn't sure he could smoke the whole thing. Three inhalations of the cigarettes he gets at the cannabis clubs are plenty. But the government-issued cigarettes are weaker. Robert kept smoking. "One of the reasons I'm in the study, I want to be part of showing that it's effective," he said. "So I want to do my part." With AIDS, Robert has lived a cat's life, dodging death time and again with the help of new drugs. But the drugs have caused grief, too. One medicine he began in January 2001 triggered the pain in his hands and feet. His doctor lowered the dose, and Robert's hands settled into a quiet numbness, but his feet are still prone to a hot, achy soreness that feels like he's walking on bare bones. Even taking two different painkillers, he rates the pain five or higher on a scale of one to 10. In the hospital, the marijuana knocked it to zero for almost the entire time between doses. To qualify for the study, Robert had to abstain from marijuana for 30 days beforehand. Normally, he smokes once a week, which isn't enough to be pain-free, but provides some relief. "There's always a balance between wanting to manage your pain and wanting to be lucid, wanting to function," he said. Smoking three times a day most days in the hospital -- at 8 a.m., 2 p.m. and 8 p.m. -- Robert was fuzzy for about 90 minutes after each dose. "There are times when I feel pretty high, like wooo!" he said, midway through his stay. "The morning thing is the hardest. You're just getting up, you're already spacey. ..."So I wake up, and I try to do, like, all my showering, making the bed and opening the window because I know after that (cigarette), nothing's going to get done." He flashed an impish smile. Usually, he took the marijuana alone in his fifth-floor room, a fan venting the smoke to the outdoors, a nurse watching through a window from the hallway.The distinctive, pungently sweet odor of marijuana can make for an awkward situation in a hospital. Once, Abrams visited as Robert took a dose. The doctor stepped out five minutes later looking abashed."I've got to go see patients, and I smell like smoke!" he gasped. THC is available in a pill, but it doesn't seem to work as well. Dr. Mark Wallace, a pain specialist at UC San Diego who plans to study the painkilling effects of smoked marijuana in healthy adults, said inhaled cannabis goes right to the bloodstream, almost as directly as an injection. He said some pharmaceutical companies are trying to develop inhalers to deliver marijuana. Robert would just as soon take the drug some other way. He found the smoke bothersome. Grown in Mississippi, the government marijuana arrives freeze-dried and must be carefully humidified before use. At UCSF, it's kept in a padlocked refrigerator in the pharmacy. A nurse weighs each cigarette before it's smoked, then collects the ashes and butt for return to the federal government. On Friday, Robert's first day home after smoking 19 cannabis cigarettes in seven days, he reported feeling a mild sinus irritation from the smoke. Otherwise, he said, he felt good. In coming weeks, dozens of other subjects will enroll in cannabis studies in the state. The Center for Medicinal Cannabis, which is managed by the University of California, has selected 11 for funding so far; eight have the federal go-ahead. Center director Dr. Igor Grant said that while most studies will run two or three years, results might emerge sooner. "The studies are designed to develop some answer," he said. "If there's a very, very clear effect, we may know sooner." The existence of the center has advanced the field already, unleashing pent-up interest. Many of the scientists with pending cannabis projects long have wanted to study the plant but were daunted by the legal tangles. "Oh gosh, the regulatory minutiae you'd have to go through!" said Wallace, the pain specialist. Marijuana is a Schedule I drug, meaning the government recognizes no medical benefit. Research proposals involving marijuana are scrutinized by four federal agencies: the Department of Health and Human Services, the Food and Drug Administration, the Drug Enforcement Agency, and the National Institute on Drug Abuse. State Sen. John Vasconcellos, D-Santa Clara, sponsor of the legislation that created the state cannabis center, cheered its progress last week. "They've worked heroically and systematically and credibly," he said. Abrams' AIDS neuropathy study was one of the first to be approved by the center, back in the fall of 2000. Abrams acknowledged it's been a long haul, but he's not looking back. "I hope this is ushering in a new era in marijuana studies," he said.