Source: Seattle Times (WA) Contact: http://www.seattletimes.com/ Copyright: 1998 The Seattle Times Company Pubdate: 22 Oct 1998 Author: Carol M. Ostrom, Seattle Times staff reporter Will medical-marijuana initiative ease their pain? Is marijuana a safe and effective medication? Medical practitioners, drug-prevention specialists and even scientists give very different answers. Some claim there is no research. Others claim there is, but say it's not good research. Still others believe there's good research - but disagree about whether it shows marijuana is dangerous or safe and effective. Yet another group claims that while there isn't good research, there are very good stories. When it comes right down to it, emotion, not science, divides many people on Initiative 692, which would legalize the use and possession of marijuana by patients with terminal or chronically debilitating conditions. Research, including new work in pain relief and brain-cell protection, is promising but still inconclusive. And medical marijuana, like abortion, is an issue that brings out deeply held beliefs. On one side are the advocates, such as Dr. William O. Robertson, a pediatrician and medical toxicologist who is a past president of the Washington State Medical Association. "I'm biased," concedes Robertson. "I think patients should be enabled to make a choice. If they really believe this stuff is going to work, I have to say, why not give it to them?" Compared to smoking cigarettes, getting drunk on alcohol or even taking many other medications, "the risk is trivial," he says. "Will it make life more tolerable for patients whose lives are simply miserable? I strongly believe that it will." On the other side are opponents, many of whom believe marijuana is harmful to human beings physically, psychologically and socially. "Prescribing a smoked, psychoactive weed for conditions for which we already have excellent legitimate medicine borders on malpractice," argued Wayne Roques, a Florida drug-prevention consultant, in a column in Alcoholism & Drug Abuse Week. Prescribing marijuana, he argues, is like prescribing a pint of whiskey to treat depression. "Compassion that harms is cruelty," he concluded. These days, many people know patients who have used marijuana. But the questions linger: What are the facts? What is the research? First, a snippet of history. Once upon a time, the leafy green stuff called marijuana was legal. The only plant known to contain cannabinoids such as THC, marijuana had common medicinal uses. In the early 1900s, Sir William Osler, the father of modern medicine, proclaimed it as "probably the most satisfactory remedy" for migraine. As concern about recreational drug use grew, Congress passed the Controlled Substances Act in 1970. Marijuana was placed in the most restrictive category, Schedule I. Schedule I drugs, by definition, have no accepted medical use, a high potential for abuse, and cannot be used safely even under a doctor's supervision. For researchers, the classification made marijuana extremely difficult to obtain. In 1988, a federal administrative law judge recommended moving marijuana to a less restrictive schedule. In its natural form, the judge ruled, marijuana is "one of the safest therapeutically active substances known to man. . . . One must reasonably conclude that there is accepted safety for use of marijuana under medical supervision." He was overruled by the federal Drug Enforcement Administration. But a growing number of patients, families and medical people began claiming marijuana helped combat nausea, pain or other conditions. Were these anecdotes nothing but hot air, like rumors in the '70s that peanut butter would cure genital herpes? Or were these the stories of human guinea pigs, much like the six soldiers who first received penicillin, whose experiences were early evidence of a valuable medication? For years, the demand for research slammed into the government's lock on legal marijuana. "The government says you need studies," says Dr. Lester Grinspoon, a Harvard medical school psychiatrist and author of "Marihuana: The Forbidden Medicine." "But then they will not release it to be studied clinically." In the past year, however, two noteworthy events took place. First, the National Institutes of Health (NIH) convened a panel of neutral medical experts to review all available data - a "Workshop on the Medical Utility of Marijuana." The panel's report was issued last year. Then, the NIH awarded money - and marijuana - to a California researcher to study marijuana's safety for HIV-positive patients. Dr. Donald Abrams, an oncologist at the University of California at San Francisco, was elated after earlier futile attempts to get approval for research. "I've got one million dollars and 1,400 joints," he chortled. The two-year study will look at the safety of smoked marijuana and Marinol, a synthetic version of THC, marijuana's main active ingredient, when taken with a commonly prescribed anti-HIV drug by patients. So far, one of Abrams' biggest problems is potential study subjects balking at the requirement that they give up marijuana for 30 days. "They say that's how they keep their pills down." Personal testimonials Anecdotes may be convincing, and there's no doubt a placebo effect can take place, but physicians must insist on scientific data when it comes to marijuana, argues Dr. Peter Marsh, past president of the Washington State Medical Association (WSMA). "In actual fact, there is no data" on marijuana's claimed medical usefulness, he told delegates to the recent WSMA convention. The organization voted not to endorse Initiative 692. Much of the research on smoked marijuana was conducted in the '70s, Abrams says, and involved a small number of subjects, poor quality research and flawed methodology. In recent years, anecdotes, more than data, have driven the medicinal marijuana movement. There's the story of Ralph Seeley, a Tacoma lawyer who died last year of bone cancer. Painting a vivid picture of lying in his own vomit after chemotherapy, Seeley sued the state, arguing that he had a constitutional right "to be free of unnecessary suffering." The state Supreme Court didn't agree. But the ruling hasn't stopped the anecdotes. Patients, including dangerously thin AIDS patients, it seems, get the "munchies" just like recreational users. They tell stories of hasty trips to the bathroom detoured by a toke or two into meandering raids on the refrigerator. Another patient, Margaret Denny, a 48-year-old former teacher from Maple Valley, began using marijuana, smoked and in tea, about five years ago. Severely injured in a 1979 head-on collision that required multiple surgeries, she was often disabled by pain and nausea. Some medications left her so zonked she couldn't function. Others had scary side effects such as destroying a patient's liver. Finally, a doctor suggested she try marijuana, and she did. She resumed life, earning a degree in computer programming. "If it hadn't been for marijuana, I wouldn't have been able to go back to school," she said. "It works the best of anything I've tried." Reefer madness? But is smoking marijuana safe? In a 1996 NIH memo rejecting one of Abrams' earlier research proposals, government-selected reviewers enumerated a long list of perceived dangers. Among them were smoking-related respiratory risks, possible DNA damage, injuries resulting from intoxication and immune-system inhibition. They also listed mental and "neurobehavioral" effects such as anxiety and anger. It's true that test-tube and animal studies hint that marijuana may harm lungs and immune systems. Other research has associated it with short-term mood disorders as well as temporary elevations of heart rate. The NIH panel also noted that the few studies on smoked marijuana used young, healthy male volunteers, suggesting little about possible dangers to older, sicker patients. Since large numbers of HIV and AIDS patients now smoke marijuana, further research on lung and immune-system effects is necessary, concludes Dr. John Morgan, a pharmacology professor and co-author of "Marijuana Myths, Marijuana Facts: A review of the Scientific Evidence." However, there is now no basis for "dire warnings of immune damage," he and co-author Lynn Zimmer conclude. Morgan and Zimmer note that immune-impaired patients risk contracting a lung disease caused by a fungus. Studies also show marijuana impairs lung-clearing cells. Although marijuana's effects are "much less pronounced" than those of tobacco smoke, Morgan adds: "Smoking isn't good for your lungs." For the most part, however, test-tube and animal studies haven't translated into findings on actual patients. Studies simply haven't found proof of lasting physical or genetic damage in long-term, heavy marijuana smokers. Some observers also note that Marinol was given FDA approval almost 15 years ago and is available by prescription for nausea. Many who look carefully at marijuana say the most striking finding is how safe it is. "There has not been a single recorded death from overdose of marijuana in recorded history," Grinspoon says. "There aren't many drugs you can say that about." The NIH panel agreed, noting that there is no known lethal dose. May be useful in several areas Even if it's safe enough, is there proof marijuana helps patients? It appears to have potential medical usefulness, warranting further study, in several areas, the NIH panel concluded. - -- Nausea and vomiting: The majority of reports, the panel concluded, showed that oral THC helped control nausea and vomiting. In one 1988 trial, 78 percent of patients who failed with other drugs rated smoked marijuana effective. The panel said inhaled marijuana's potential in this area "merits testing" in further studies. - -- Appetite stimulation and "wasting" syndrome: The panel concluded there is a "strong relationship" between smoking marijuana and appetite, though research didn't prove this was a long-term effect. Weight gain in perilously thin AIDS patients with "wasting" syndrome has been anecdotally associated with oral THC, but there haven't been studies. Marinol was most providers' second choice after another drug; a study now under way at the National Cancer Institute is comparing the two. - -- Pain relief: The NIH panel, which didn't consider some recent significant research, concluded it "highly likely" that smoked marijuana helps some kinds of pain. In one study of THC's effects on cancer patients, pain-relief effects of THC and codeine were similar and significant. Smoked marijuana likely allows a more precise dose than oral THC, the panel noted, but a dose big enough to relieve pain might also cause unwanted side effects. - -- Spasms and neurological effects: There is good evidence, from clinical trials and anecdote, that marijuana can help control convulsions or spasms, and may have potential in conditions such as epilepsy, multiple sclerosis and spinal-cord injury, the panel said. - -- Glaucoma: Animal studies are conflicting, and effects on human glaucoma have "never been investigated by modern means," the panel noted. While there are other good treatments available, marijuana might help patients who have an incomplete response, the panel said. Intriguing findings In addition, recent research on THC has produced intriguing findings not addressed by the panel. - -- Brain injury and stroke: Most amusing to some marijuana activists, recent research suggests that smoking pot may actually protect brain cells from damage. Scientists at the NIH found that two of marijuana's cannabinoids appear to protect brain cells when neurons are deprived of oxygen, as occurs during a stroke. Like most research on marijuana or its components, this wasn't done on human patients, but in a test tube. But researchers have long noted the presence of receptors for cannabinoids in the human brain. - -- Marijuana, morphine and pain: Ian Meng's recent study at UC-San Francisco showed that marijuana and morphine, in rats' brains, act on the same neuron circuits. Using a chemical mimic of THC, Meng found that both THC and morphine turn off pain messages. Meng, a post-doctoral student in the department of neurology, says previous research pointed in the same direction. "I don't think there's much doubt now." Of course, the big question is always whether animal studies can be extrapolated to effects on humans. As the debate nears Election Day here and in several other states, more parties have joined the fray. The war on drugs notwithstanding, a number of groups have called for research on marijuana as medicine, including the conservative American Medical Association. Federal policies that prohibit prescribing marijuana, editorialized The New England Journal of Medicine, are "misguided, heavy-handed and inhumane." Morgan, the pharmacology professor, predicts a new day dawning for marijuana. The proof, he claims, is in the profits: Pharmaceutical companies are already scrambling to develop nasal sprays, lozenges, vaporizers, suppositories and skin patches to deliver marijuana's active ingredients to a patient, sans smoke. - --- Checked-by: Mike Gogulski