MARIJUANA AS MEDICINE Medical Use Of This Illegal Plant Has Been A 30-year Controversy Some argue that marijuana is an effective pain reliever and anti-inflammatory and now some research is showing they may be right. Over the past 11 years, rheumatoid arthritis (RA) has invaded Tom Flowers' hips, knees, feet and hands and put him in a wheelchair. At this point, he can't walk and his hands are so gnarled he's forced to type with one finger. He goes through a lengthy ritual each morning just to get going. First he takes a cool shower and an array of prescription drugs that includes Celebrex, prednisone, Arava and codeine. And then he lights up a joint, the first of three he will smoke that day. The marijuana helps ease his pain and especially helps with muscle spasms, Flowers says. Some others with arthritis seem to agree: A 1998 survey of about 1,000 medical marijuana users at the Oakland (California) Cannabis Buyers Cooperative showed 14 percent were using marijuana for arthritis or "rheumatism." "It keeps me going," says Flowers. "I'd like to stop all of the drugs if I could but people don't understand that. They think if you are using marijuana you are abusing it." In fact, the intoxication marijuana brings him has become more of an inconvenience than a pleasure. "I try to avoid being high all the time," says Flowers, who has a small publishing business and consults on horticulture. "There are other things I'd rather do, and being high slows me down. But when you are in a lot of pain, it's worth it." For Flowers, 50, who lives in the San Francisco Bay area, medical use of marijuana is legal, at least for now. He buys marijuana at a reasonable price from the Oakland buyers co-op. California is one of eight states where medical use of marijuana is permitted to varying degrees to relieve the symptoms of serious conditions, such as arthritis, cancer, anorexia, AIDS, chronic pain, spasticity, glaucoma and migraine. The other states that allow some medical use are Alaska, Washington, Oregon, Arizona, Nevada, Maine and Hawaii. Surveys, however, show the public does not approve of legalizing marijuana for recreational use, and possession is still a federal crime. So while California's liberal laws may allow Flowers to use marijuana medically, under federal law he's a criminal who could face years of jail time if charged and convicted. Research Shows Surprising Results Flowers and patients like him are at the heart of the storm a controversy that has been in the courts and public consciousness for more than 30 years as individuals and groups like the National Organization for Reform of Marijuana Laws (NORML) have campaigned for decriminalization of medical marijuana. But because millions of Americans use marijuana recreationally (and illegally) for its psychoactive and intoxicating effects, acceptance of its known or potential medical benefits has been slow. It is best known medically for its ability to relieve the nausea, vomiting and weight loss connected with cancer chemotherapy and AIDS. But it has also long been used for chronic pain and a range of musculoskeletal ills that include many kinds of arthritis. Although marijuana research on humans has been limited, animal studies show that its active ingredients, called cannabinoids, help suppress pain as well as opiates like morphine, but without some of the unwanted effects, such as addiction and nausea. Cannabinoids could be used along with opiates to enhance pain control, lowering the dose needed to offer relief. A Phase I clinical trial conducted in Paris this summer found that a synthetic derivative of tetrahydrocannabinol (THC), a major psychoactive component of marijuana, relieved pain and reduced inflammation without producing psychogenic effects. In a new study released in August, the authors say their research shows one of the cannabinoids, called cannabidiol, suppressed progression of disease and joint damage in mice that had been injected with collagen to produce an arthritis-like disease. The study, from the Kennedy Institute of Rheumatology in London and Hebrew University in Jerusalem, also showed that cannabidiol suppressed the release of tumor necrosis factor (TNF), which is known to contribute to RA, in test tube studies of cells from these mice. Even though they distilled cannabidiol from a powerful, concentrated form of marijuana called hashish, it is not psychoactive and wouldn't make users "high." Study author Marc Feldmann, MD, PhD, of the Kennedy Institute of Rheumatology and a major TNF researcher, was cautiously optimistic. "When it works in mice, you're happy," he says, "but that's no guarantee it will work in humans. However, this is a pure pharmaceutical compound that doesn't have psychoactive effects, so it can be taken seriously as a drug." Co-author Raphael Mechoulam, PhD, of Hebrew University, a natural products chemist and pioneer in the research of medical marijuana, says human studies have shown marijuana prevents brain damage from head injuries and holds promise for treating stroke, rheumatoid arthritis, multiple sclerosis, Tourette's syndrome and possibly even Parkinson's disease. Mechoulam has been studying medical uses of the plant at his lab in Israel for the past 35 years. Because marijuana is illegal in Israel, he works with confiscated cannabis supplied to him by the police. Its legal status, he believes, has hobbled human medical research. "The medical community for years has tried to distance itself from marijuana and its constituents," according to Mechoulam. "Their attitude was, `It's too political, marijuana is an illicit drug.' "This attitude has probably delayed the medical uses of cannabinoids. For example, for years I tried to get a clinical study of THC on multiple sclerosis in this country [Israel] and none of the major departments of neurology were willing to go ahead with it," Mechoulam explains. That's illogical, says Mechoulam. Morphine, which is sometimes used recreationally, has been the major drug against pain for 100 years or more, "and there is no stigma in using morphine medicinally," he says. "So why should there be a stigma against another drug that may have recreational uses?" Mechoulam, who is sometimes called "the guru of cannabinoid research," points out that more than half of today's drugs are derived from natural products, and marijuana could be one of them. Our bodies may even be wired for cannabis: Studies show that we have brain cell receptors for cannabinoids, such as delta-9-tetrahydrocannabinol, which is better known as THC. Our body even makes some cannabinoid-like substances called anandamides. "The spinal cord is loaded with cannabinoid receptors," says J. Michael Walker, PhD, chairman of psychology at Brown University in Providence, R.I., and a professor of neuroscience. "These cannabinoid compounds apparently reduce swelling from inflammation," explains Walker, who has been researching marijuana and pain for more than a decade. "But more than that, they kill the pain from inflammation specifically. They work on the peripheral nerves that carry pain from your joint into the spinal cord." Mechoulam says attitudes about marijuana research in humans may be changing, spurred in part by positive reports from prestigious committees in several countries, such as the House of Lords Committee in the United Kingdom and the independent National Academy of Sciences Institute of Medicine in the United States. These have urged more research into medical marijuana. "I do hope that with these strong recommendations more clinical trials are to be done," says Mechoulam. The medical use of marijuana got a big boost last year when a panel from the Institute of Medicine concluded that marijuana is not addictive, does not act as a gateway to harder drug use, and can help ease pain, nausea and appetite loss from cancer chemotherapy and AIDS. Surprisingly, the panel of scientists, acknowledging that research will take time, recommended that people with serious illness be given legal access now to marijuana for medical use. The study by Dr. Feldmann and Mechoulam prompted Stephen E. Straus, MD, the head of the National Center for Complementary and Alternative Medicine (NCCAM) to say cannabidiol potentially could lead to whole new classes of medications to inhibit arthritis inflammation. Walker agrees. "I'm not saying people should go smoke it, but there is no doubt in my mind that the compounds of cannabinoids reduce pain and inflammation, at least in animals," he says. Smoking Anything Still Is Dangerous But some powerful drawbacks tend to be downplayed by medical marijuana proponents. The Institute of Medicine's report also found marijuana smoke is much more toxic than tobacco smoke, and urged research into synthetic forms and smokeless delivery systems. Cigarette for cigarette, the smoke of marijuana is by far more harmful to the lungs than tobacco smoke, says Donald Tashkin, MD, a pulmonary expert who has studied the effects of marijuana on the lungs for decades. "Marijuana smoking deposits four times as much tar in the lungs as tobacco smoking for the same amount of material smoked," Dr. Tashkin says. He adds that it very likely increases the risk of lung cancer. Dr. Tashkin also says marijuana is a powerful immune suppresser as well, citing effects of THC on a wide variety of immune cells such as alveolar macrophages, which destroy bacteria and fungi in the lungs, and T-cells, which modulate the body's defense against both infection and cancer. But Walker and others aren't so sure. "Cannabinoids modulate the immune system," he says. "They have complex effects, and the full extent of their actions isn't understood yet." Could immune suppression be helpful to those with over-active immune systems, as in RA? "Immune suppression is a two-edged sword," says Dr. Tashkin. "On the one hand, there's concern about the body's ability to mount a defense against infection; on the other hand, you take somebody with an autoimmune disease like RA and the positive effects may outweigh the negative. There are risks and benefits to everything." Bottom line: Medical marijuana needs more human research. In the United Kingdom, studies are underway now involving humans, and in Canada a major clinical trial with smoked marijuana will begin soon, says Walker. Dr. Tashkin agrees. "The way to exploit the therapeutic potential of marijuana is to develop highly specific products that produce the effect you want, and not the side effects. It makes no sense to inhale thousands of ingredients in marijuana smoke you know are carcinogens and other toxins in order to deliver one that is useful." There is a legal alternative to smoking marijuana. A synthetic version of pure THC is available in a pill called Marinol that has been marketed since 1986 exclusively as an appetite stimulant or an anti-emetic. Some patients who take it for pain which is not an approved use complain that it isn't as effective, that it's hard to judge the right dosage, and that it actually gets you "higher" than smoked marijuana. Walker says Marinol does have drawbacks. It's absorbed slowly and unpredictably, he says, so you can't control the dose. And it costs more a lot more than marijuana: In San Francisco, for example, a single Marinol pill costs $4 to $16, depending on dosage. Marijuana can be and is eaten, usually blended into foods. But this method has the same problems as Marinol pills in that the dose and effect are more difficult to calculate. It takes longer to feel an effect, and people may take too much or too little. It also takes more marijuana. When smoked, the user can tell almost immediately if there is an effect, how much is needed, and when to stop, says Lester Grinspoon, MD, a Harvard University emeritus professor of psychiatry and expert on marijuana. But Dr. Tashkin says he is skeptical about arguments from marijuana proponents that smoking is better than pills. "That's a smoke screen to legalize recreational marijuana," he says. Scientists are looking at other methods of delivering marijuana's medicinal materials without the carcinogens. A vaporizer that heats the herb gently, releasing its effects at temperatures too low to burn it, is being tried now. Other ideas include an atomizer similar to the kind used by allergy and asthma sufferers or suppositories that can deliver the drug without the smoke. A project at the Albany (New York) College of Pharmacy has a $361,000 grant from the American Cancer Society to develop a transdermal patch that would deliver active cannabinoid ingredients through the skin, the same way a nicotine patch works. The Drug Enforcement Agency, which regulates all research with illegal drugs, has approved the project. The Smoke and Fire of Debate However, research on medical marijuana is unlikely to allay criticism about smoking an illegal and potentially toxic substance. Many people, including doctors and researchers, agree with the federal government position that the medical push is a ploy for those who want legalized recreational use. On the other hand, there are plenty of doctors who support medical use of marijuana, according to NORML. One of the most outspoken is Dr. Grinspoon, the author of several books on marijuana including, Marijuana: The Forbidden Medicine. He says marijuana is a safe and non-toxic drug that relieves a range of symptoms and ailments. He saw marijuana's beneficial effects on chemotherapy reactions firsthand when his son, Danny, was dying of cancer. "It doesn't cure anything," Dr. Grinspoon says, "But there are so many symptoms it relieves, including pain. It has eased terrible suffering for so many. A number of elderly people say you have no idea how helpful this has been for their osteoarthritis or their MS [multiple sclerosis]." Dr. Grinspoon says many users of medical marijuana are nonsmokers whose pain finally drove them to consider inhaling an illegal and potentially toxic herb. Some have had to be taught to smoke by their grandchildren. But the image of elderly people or anybody lighting up a joint doesn't sit easily with many. There's such a strong stigma connected to marijuana use that several rheumatologists contacted declined to comment at all, as did several people using it for arthritis symptoms. But other doctors like Robert W. Ike, MD, an associate professor and rheumatologist at the University of Michigan in Ann Arbor, say they know arthritis patients use marijuana, regardless of its legality. "I have a few patients who freely admit they smoke marijuana as part of their treatment for pain, along with [taking] prescription drugs," Dr. Ike says. "It's not legal in Michigan, but I'm past the point of being shocked." Dr. Ike's opinion? Marijuana has value as a pain reliever and antidepressant. "I'd do it in a minute if I had arthritis," he says. "I've seen what a devastating disease it is, and I'd turn to anything that would help." But other rheumatologists say they haven't seen any evidence about marijuana that justifies using a drug that hasn't been researched for arthritis use, and that's illegal under federal law. "I do not advocate the use of marijuana for chronic pain," says Robert Bennett, MD, a fibromyalgia specialist at Oregon Health Sciences University in Portland. "A few of my patients use it, but still require pain medication. The Institute of Medicine report on the medical use of marijuana last year came to the conclusion that it may have a role in the treatment of pain, but more work needs to be done." James McKoy, MD, a rheumatologist with Kaiser Permanente in Hawaii and a member of the Arthritis Today medical advisory board, says he's had numerous patients asking about marijuana, most of them baby boomers with some experience using it or other illegal drugs recreationally. But Dr. McKoy isn't convinced it has much to offer over conventional drugs, and he won't recommend or prescribe it. "I have one patient with rheumatoid arthritis who uses it for pain and, other than getting a `high,' it hasn't reduced any of her needs for DMARDs [disease-modifying antirheumatic drugs], NSAIDs, prednisone or Vicodin. I see no change in her complaints of pain," says Dr. McKoy. Still a Dangerous Drug . . . Legally Doctors are concerned about their legal vulnerability if they were to recommend marijuana, but according to NORML, they are at less risk than their patients who use the drug. "We get many dozens of e-mails a week asking about doctors' legal status. It's more of a risk in their minds than in reality," says Allen St. Pierre, executive director of the NORML Foundation. Doctors making a medical recommendation won't be prosecuted for communicating with patients, he claims. The shifting status of marijuana shows that the medical profession is taking chronic pain seriously, says Walker, and willing to look into previously taboo areas to help relieve suffering. "If you think about the worst kind of pain imaginable and to me that's nerve injury opiates don't work," he says. "The pain is so extreme that some people commit suicide. In animals, cannabinoids are extremely effective against these kinds of pain." Randi Webster, 44, co-director of the San Francisco Patients Resource Center, has been using cannabis medicinally for RA for 20 years for pain control. She uses a water pipe at home, but otherwise has to have people roll joints for her. "My fingers don't work so well anymore," she says. Webster has been arrested in the past, and recognizes that she could be charged again, but says she and many others using medical marijuana are not afraid to speak out. "We're changing history here," she says, " I stand up for what I believe in. We'll keep on being busted until we don't get busted any more." When all the dust settles, and when marijuana is admitted to the U.S. Pharmacopoeia, "it will be seen as one of the least toxic drugs in the whole compendium," predicts Dr. Grinspoon. Pro: "I'd [use marijuana] in a minute if I had arthritis. I've seen what a devastating disease it is, and I'd turn to anything that would help." Robert W. Ike, MD, Rheumatologist "These cannabinoid compounds apparently reduce swelling from inflammation. But more than that, they kill the pain from inflammation specifically." J. Michael Walker, PhD, Neuroscience Professor "It doesn't cure anything, but there are so many symptoms it relieves, including pain. It has eased terrible suffering for so many." Lester Grinspoon, MD, Psychiatry Professor Con: "I do not advocate the use of marijuana for chronic pain. A few of my patients use it, but still require pain medication." Robert Bennett, MD, Fibromyalgia Specialist "Marijuana smoking deposits four times as much tar in the lungs as tobacco smoking." Donald Tashkin, MD, Pulmonary Specialist "I have one patient with rheumatoid arthritis who uses it for pain and, other than getting a `high,' it hasn't reduced any of her needs for DMARDs, NSAIDs, prednisone or Vicodin." James McKoy, MD, Rheumatologist Marijuana Wasn't Always Illegal arijuana wasn't always the wicked weed. Originally from Asia, cannabis has been cultivated and used as a helpful herbal medicine in many cultures for more than 5,000 years. Ancient writings recommend it for a range of ailments including malaria, insomnia, headache, depression, childbirth pain, weight loss and "rheumatism." Some 4,000 years ago, it was listed in a Chinese botanical text as an herb that reverses rheumatism. A century ago, it was generally accepted as a medicine in Europe and the United States. It has been made into drinks, tinctures and poultices, mixed into foods and, most often, smoked. It's also been widely used as a mood-altering and intoxicating substance. In the mid-1800s, cannabis became a popular remedy in the West for a range of ailments, but especially for pain. It could be bought in some drugstores, and it's said that Queen Victoria's doctor gave it to her to ease menstrual cramps. However, its medical use began to fade in the early 1900s as alternative pain drugs such as aspirin became available, and as the invention of the hypodermic needle made it possible to inject narcotics such as morphine for faster pain relief. While medicinal use declined, recreational use of marijuana continued and generated stories that "reefer madness" caused violence and addiction (now known to be untrue). The 1937 Marijuana Tax Act outlawed recreational use and made it so difficult for doctors to get cannabis that medical use faded away. The liberal 1960s brought recreational use back with a bang. By 1979, it was estimated that 30 percent of young Americans smoked marijuana. Some states were decriminalizing it until the backlash of the War on Drugs in the 1980s led lawmakers to stiffen criminal penalties for marijuana possession or sale. But by then, its medicinal uses had been rediscovered. People undergoing cancer treatment found marijuana could relieve suffering from nausea and the often violent vomiting caused by chemotherapy. It was believed to help glaucoma by lowering pressure in the eye, and the swelling ranks of AIDS patients discovered that marijuana not only eases pain and nausea but also helps with weight gain by stimulating appetite. In the 1970s, a person with glaucoma sued the federal government after his arrest and won the right to a government-grown supply on the grounds of medical necessity. The Compassionate Investigative New Drug program was established to provide government-grown marijuana for some patients, but in 1991 officials quit accepting applications because of the deluge of requests from AIDS patients. It serves only eight patients today, in spite of an unsuccessful class action suit brought by 200 people. Today, marijuana remains a controversy and a problem for those who would use it for medical reasons. Eight states have legalized its medical use to varying degrees, but under federal law even medical marijuana use is a crime.
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