Pubdate: April-May 2000 Source: Policy Review (US) Copyright: 2000 Policy Review Pages: 51- 61 Contact: 214 Massachusetts Ave. NE, Washington, DC 20002 Fax: (202) 608-6136 Website: http://www.policyreview.com/ Author: James R. McDonough Note: James R. McDonough is director of the Florida Office of Drug Control. Also: At least two articles have been published which reference this article. They are at: http://www.mapinc.org/drugnews/v00/n417/a01.html http://www.mapinc.org/drugnews/v00/n453/a08.html MARIJUANA ON THE BALLOT While it has long been clear that chemical compound found in the marijuana plant offer potential for medical use, smoking the raw plant is a method of delivery supported neither by law nor recent scientific evidence. The Food and Drug Administration's approval process, which seeks to ensure the purity of chemical compounds in legitimate drugs, sets the standard for medical validation of prescription drugs as safe and effective. Diametrically opposed to this long-standing safeguard of medical science is the recent spate of state election ballots that have advocated the use of a smoked plant - the marijuana leaf - for "treating" an unspecified number of ailments. It is a tribute to the power of political activism that popular vote has displaced objective science in advancing what would be the only smoked drug in America under the guise of good medicine. Two recent studies of the potential medical utility of marijuana advocate development of a non-smoked, rapid onset delivery system of the cannabis compounds. But state ballot initiatives that seek legalization of smoking marijuana as medicine threaten to circumvent credible research. Advocates for smoking marijuana appear to want to move ahead at all costs, irrespective of dangers to the user. They make a well-financed, emotional appeal to the voting public claiming that what they demand is humane, useful, and safe. Although they rely largely on anecdote to document their claims, they seize upon partial statements that purport to validate their assertions. At the same time, these partisans - described by Chris Wren, the highly respected journalist for the New York Times, as a small coalition of libertarians, liberals, humanitarians, and hedonists - reject the main conclusions of medical science: that there is little future in smoked marijuana as a medically approved medication. A Dearth Of Scientific Support Compounds found in marijuana may have medical potential, but science does not support smoking the plant in its crude form as an appropriate delivery system. An exploration of two comprehensive inquiries into the medical potential of marijuana indicates the following: o Science has identified only the potential medical benefit of chemical compounds, such as THC, found in marijuana. Ambitious research is necessary to understand fully how these substances affect the human body. o Experts who have dealt with all available data do not recommend that the goal of research should be smoked marijuana for medical conditions. Rather, they support development of a smoke-free, rapid-onset delivery system for compounds found in the plant. In 1997, the National Institutes of Health (NIH) met "to review the scientific data concerning the potential therapeutic uses of marijuana and the need for and feasibility of additional research." The collection of experts had experience in relevant studies and clinical research, but held no preconceived opinions about the medical use of marijuana. They were asked the following questions: What is the current state of scientific knowledge; what significant questions remain unanswered; what is the medical potential; what possible uses deserve further research; and what issues should be considered if clinical trials are conducted? Shortly thereafter, the White House Office of National Drug Control Policy (ONDCP) asked the Institute of Medicine (IOM) to execute a similar task: to form a panel that would "conduct a review of the scientific evidence to assess the potential health benefits and risks of marijuana and its constituent cannabinoids." Selected reviewers were among the most accomplished in the disciplines of neuroscience, pharmacology, immunology, drug abuse, drug laws, oncology, infectious diseases, and ophthalmology. Their analysis focused on the effects of isolated cannabinoids, risks associated with medical use of marijuana, and the use of smoked marijuana. Their findings in the IOM study stated: "Compared to most drugs, the accumulation of medical knowledge about marijuana has proceeded in reverse. Typically, during the course of drug development, a compound is first found to have some medical benefit. Following this, extensive tests are undertaken to determine the safety and proper dose of the drug for medical use. Marijuana, in contrast, has been widely used in the United State for decades .... The data on the adverse effects of marijuana are more extensive than the data on effectiveness. Clinical studies of marijuana are difficult to conduct." Nevertheless, the IOM report concluded that cannabinoid drugs do have potential for therapeutic use. It specifically named pain, nausea and vomiting, and lack of appetite as symptoms for which cannabinoids may be of benefit, stating that cannabinoids are "moderately well suited" for AIDS wasting and nausea resulting from chemotherapy. The report found that cannabinoids "probably have a natural role in pain modulation, control of movement, and memory," but that this role "is likely to be multi-faceted and remains unclear." In addressing the possible effects of smoked marijuana on pain, the NIH report explained that no clinical trials involving patients with "naturally occurring pain" have ever been conducted but that two credible studies of cancer pain indicated analgesic benefit. Addressing another possible benefit - the reduction of nausea related to chemotherapy - the NIH report described a study comparing oral administration of THC (via a drug called Dronabinol) and smoked marijuana. Of 20 patients, nine expressed no preference between the two, seven preferred the oral THC, and only four preferred smoked marijuana. In summary, the report states, "No scientific questions have been definitively answered about the efficacy of smoked marijuana in chemotherapy-related nausea and vomiting." In the area of glaucoma, the effect of marijuana on intraocular pressure (the cause of optic nerve damage that typifies glaucoma) was explored, and smoked marijuana was found to reduce this pressure. However, the NIH report failed to find evidence that marijuana can safely and effectively lower intraocular pressure enough to prevent optic nerve damage." The report concluded that the "mechanism of action" of smoked marijuana or THC in pill form on intraocular pressure is not known and calls for more research. In addressing appetite stimulation and wasting related to AIDS, the NIH report recognized the potential benefit of marijuana. However, the report also noted the lack of pertinent data. The researchers pointed out that the evidence known to date, although plentiful, is anecdotal, and "no objective data relative to body composition alterations, HIV replication, or immunologic function in HIV patients are available." Smoking marijuana as medicine was recommended by neither report. The IOM report called smoked marijuana a "crude THC delivery system" that is not recommended because it delivers harmful substances, pointing out that botanical products are susceptible to problems with consistency, contaminations, uncertain potencies, and instabilities. The NIH report reached the same conclusion and explained that eliminating the smoked aspect of marijuana would "remove an important obstacle" from research into the potential medical benefits of the plant. These studies present a consistent theme.- Cannabinoids in marijuana do show potential for symptom management of several conditions, but research is inadequate to explain definitively how cannabinoids operate to deliver these potential benefits. Nor did the studies attribute any curative effects to marijuana; at best, only the symptoms of particular medical conditions are affected. The finding most important to the debate is that the studies did not advocate smoked marijuana as medicine. To the contrary, the NIH report called for a non-smoked alternative as a focus of further research. The IOM report recommended smoking marijuana as medicine only in the most extreme circumstances when all other medication has failed and then only when administration of marijuana is under strict medical supervision. These conclusions from two studies, based not on rhetorical conjecture but on credible scientific research, do not support the legalization of smoked marijuana as medicine. The Scientific Community's Views The conclusions of the NIH and IOM reports are supported by commentary published in the nation's medical journals. Much of this literature focuses on the problematic aspect of smoke as a delivery system when using cannabinoids for medical purposes. One physician- authored article describes smoking "crude plant material" as "troublesome" to many doctors and "unpleasant" to many patients. Dr. Eric Voth, chairman of the International Drug Strategy Institute, stated in a 1997 article published in the Journal of the American Medical Association (JAMA): "To support research on smoked pot does not make sense. We're currently in a huge anti-tobacco thrust in this country, which is appropriate. So why should we waste money on drug delivery that is based on smoking?" Voth recommends non-smoked analogs to THC. In September, 1998, the editor in chief of the New England Journal of Medicine, Dr. Jerome P. Kassirer, in a coauthored piece with Dr. Marcia Angell, wrote: "Until the 20th century, most remedies were botanical, a few of which were found through trial and error to be helpful. All of that began to change in the 20th century as a result of rapid advances in medical science. In particular, the evolution of the randomized, controlled clinical trial enabled researchers to study with precision the safety, efficacy, and dose effects of proposed treatments and the indications for them. No longer do we have to rely on trial and error and anecdotes. We have learned to ask and expect statistically reliable evidence before accepting conclusions about remedies." Dr. Robert DuPont of the Georgetown University Department of Psychiatry points out that those who aggressively advocate smoking marijuana as medicine "undermine" the potentially beneficial roles of the NIH and IOM studies. As does Dr. Voth, DuPont discusses the possibility of nonsmoked delivery methods. He asserts that if the scientific community were to accept smoked marijuana as medicine, the public would likely perceive the as influenced by politics rather than science. Dupont concludes that if research is primarily concerned with the needs of the sick, it is unlikely that science will approve of smoked marijuana as medicine. Even those who advocate smoking marijuana for medicine are occasionally driven to caution. Dr. Lester Grinspoon, a Harvard University professor and advocate of smoking marijuana, warned in a 1994 JAMA article: "The one area we have to be concerned about is pulmonary function. The lungs were not made to inhale anything but fresh air." Other experts have only disdain for the loose medical claims for smoked marijuana. Dr. Janet Lapey, executive director of Concerned Citizens for Drug Prevention, likened research on smoked marijuana to using opium pipes to test morphine. She advocates research on isolated active compounds rather than smoked marijuana. The findings of the NIH and iom reports, and other commentary by members of the scientific and medical communities, contradict the idea that plant smoking is an appropriate vehicle for delivering whatever compounds research may find to be of benefit. Enter The FDA The mission of the Food and Drug Administration's (FDA) Center for Drug Evaluation and Research is "to assure that safe and effective drugs are available to the American people." Circumvention of the FDA approval process would remove this essential safety mechanism intended to safeguard public health. The FDA approval process is not designed to keep drugs out of the hands of the sick but to offer a system to ensure that drugs prevent, cure, or treat a medical condition. FDA approval can involve testing of hundreds of compounds, which allows scientists to alter them for improved performance. The IOM report addresses this situation explicitly: "Medicines today are expected to be of known composition and quantity. Even in cases where marijuana can provide relief from symptoms, the crude plant mixture does not meet this modern expectation." For a proposed drug to gain approval by the FDA, a potential manufacturer must produce a new drug application. The application must provide enough information for FDA reviewers to determine (among other criteria) "whether the drug is safe and effective for its proposed use(s), whether the benefits of the drug outweigh its risks [and] whether the methods used in manufacturing the drug and the controls used to maintain the drug's quality are adequate to preserve the drug's integrity, strength, quality, and purity." On the "benefits" side, the Institute of Medicine found that the therapeutic effects of cannabinoids are "generally modest" and that for the majority of symptoms there are approved drugs that are more effective. For example, superior glaucoma and antinausea medications have already been developed. In addition, the new drug Zofran may provide more relief than THC for chemotherapy patients. Dronabinol, the synthetic THC, offers immunocompromised HIV patients a safe alternative to inhaling marijuana smoke, which contains carcinogens. On the "risks" side, there is strong evidence that smoking marijuana has detrimental health effects. Unrefined marijuana contains approximately 400 chemicals that become combustible when smoked, producing in turn over 2,000 impure chemicals. These substances, many of which remain unidentified, include. carcinogens. The IOM report states that, when used chronically, "marijuana smoking is associated with abnormalities of cells lining the human respiratory tract. Marijuana smoke, like tobacco smoke, is associated with increased risk of cancer, lung damage, and poor pregnancy outcomes." A subsequent study by Dr. Zuo-Feng Zhary of the Jonsson Cancer Center at UCLA determined that the carcinogens in marijuana are much stronger than those in tobacco. Chronic bronchitis and increased incidence of pulmonary disease are associated with frequent use of smoked marijuana, as are reduced sperm motility and testosterone levels in males. Decreased immune system response, which is Rely to increase vulnerability to infection and tumors, is also associated with frequent use. Even a slight decrease in immune response can have major public health ramifications. Because marijuana by-products remain in body fat for several weeks, interference with normal body functioning may continue beyond the time of use. Among the known effects of smoking marijuana is impaired lung function similar to the type caused by cigarette smoking. In addressing the efficacy of cannabinoid drugs, the IOM report - after recognizing "potential therapeutic value" - added that smoked marijuana is "a crude THC delivery system that also delivers harmful substances." Purified cannabinoid compounds are preferable to plants in crude form, which contain inconsistent chemical composition. The "therapeutic window" between the desirable and adverse effects of marijuana and THC is narrow at best and may not exist at all, in many cases. The scientific evidence that marijuana's potential therapeutic benefits are modest, that other approved drugs are generally more effective, and that smoking marijuana is unhealthy, indicates that smoked marijuana is not a viable candidate for FDA approval. Without such approval, smoked marijuana cannot achieve legitimate status as an approved drug that patients can readily use. This reality renders the advocacy of smoking marijuana as medicine both misguided and impractical. Medicine By Ballot Initiave ? While ballot initiatives are an indispensable part of our democracy, they are imprudent in the context of advancing smoked marijuana as medicine because they confound our system of laws, create conflict between state and federal law, and fail to offer a proper substitute for science. Ballot initiatives to legalize smoking marijuana as medicine have had a tumultuous history. In 1998 alone, initiatives were passed in five states, any substantive benefits in the aftermath were lacking. For example, a Colorado proposal was ruled invalid before the election. An Ohio bill was passed but subsequently repealed. In the District of Colombia, Congress disallowed the counting of ballot results. Six other states permit patients to smoke marijuana as medicine but only by prescription, and doctors, dubious about the validity of a smoked medicine, wary of liability suits, and concerned about legal and professional risks are reluctant to prescribe it for their patients. Although voters passed Arizona's initiative, the state legislature originally blocked the measure. The version that eventually became Arizona law is problematic because it conflicts with federal statute. Indeed, legalization at the state level creates a direct conflict between state and federal law in every case, placing patients, doctors, police, prosecutors, and public officials in a difficult position. The fundamental legal problem with prescription of marijuana is that federal law prohibits such use, rendering state law functionally ineffective. To appreciate fully the legal ramifications of ballot initiatives, consider one specific example. California's is perhaps the most publicized, and illustrates the chaos that can result from such initiatives. Enacted in 1996, the California Compassionate Use Act (also known as Proposition 215) was a ballot initiative intended to afford legal protection to seriously ill patients who use marijuana therapeutically. The act explicitly states that marijuana used by patients must first be recommended by a physician, and refers to such use as a "right" of the people of California. According to the act, physicians and patients are not subject to prosecution if they are compliant with the terms of the legislation. The act names cancer, anorexia, AIDS, chronic pain, spasticity, glaucoma, arthritis, and migraine as conditions that may be appropriately treated by marijuana, but it also includes the proviso: "or any other illness for which marijuana provides relief." Writing in December 1999, a California doctor, Ryan Thompson, summed up the medical problems with Proposition 215: As it stands, it creates vague, ill-defined guidelines that are obviously subject to abuse. The most glaring areas are as follows: o A patient does not necessarily need to be seen, evaluated or diagnosed as having any specific medical condition to qualify for the use of marijuana. o There is no requirement for a written prescription or even a written recommendation for its medical use. o Once "recommended," the patient never needs to be seen again to assess the effectiveness of the treatment and potentially could use that "recommendation" for the rest of his or her life. o There is no limitation to the conditions for which it can be used, it can be recommended for virtually any condition, even if it is not believed to be effective. The doctor concludes by stating: "Certainly as a physician I have witnessed the detrimental effects of marijuana use on patients and their families. It is not a harmless substance." Passage of Proposition 215 resulted in conflict between California and the federal government. In February 1997, the Executive Office of the President issued its response to the California Compassionate Use Act (as well as Arizona's Proposition 200). The notice stated: "[The] Department of Justice's (D. O. J.) position is that a practitioner's practice of recommending or prescribing Schedule I controlled substances is not consistent with the public interest (as that phrase is used in the federal Controlled Substances Act) and will lead to administrative action by the Drug Enforcement Administration (DEA) to revoke the practitioner's registration." The notice indicated that U.S. attorneys in California and Arizona would consider cases for prosecution using certain criteria. These included lack of a bona fide doctor-patient relationship, a "high volume" of prescriptions (or recommendations) for Schedule I drugs, "significant" profits derived from such prescriptions, prescriptions to minors, and "special circumstances" like impaired driving accidents involving serious injury. The federal government's reasons for taking such a stance are solid. Dr. Donald Vereen of the Office of National Drug Control Policy explains that "research-based evidence" must be the focus when evaluating the risks and benefits of any drug, the only approach that provides a rational basis for making such a determination. He also explains that since testing by the Food and Drug Administration and other government agencies is designed to protect public health, circumvention of the process is unwise. While the federal government supports FDA approved cannabinoid-based drugs, it maintains that ballot initiatives should not be allowed to remove marijuana evaluation from the realm of science and the drug approval process - a position based on a concern for public health. The Department of Health and Human Services has revised its regulations by making research-grade marijuana more available and intends to facilitate more research of cannabinoids. The department does not, however, intend to lower its standards of scientific proof. Problems resulting from the California initiative are not isolated to conflict between the state and federal government. California courts themselves limited the distribution of medical marijuana. A 1997 California appellate decision held that the state's Compassionate Use Act only allowed purchase of medical marijuana from a patient's "primary caregiver," not from "drug dealers on street corners" or "sales centers such as the Cannabis Buyers' Club." This decision allowed courts to enjoin marijuana clubs. The course of California's initiative and those of other states illustrate that such ballot-driven movements are not a legally effective or reliable way to supply the sick with whatever medical benefit the marijuana plant might hold. If the focus were shifted away from smoking the plant and toward a non-smoked alternative based on scientific research, much of this conflict could be avoided. Filling "Prescriptions" It is one thing to pass a ballot initiative defining a burning plant as medicine. It is yet another to make available such "medicine" if the plant itself remains - as it should - illegal. Recreational use, after all, cannot be equated with medicinal use, and none of the ballots passed were constructed to do so. Nonetheless, cannabis buyers' clubs were quick to present the fiction that, for medical benefit, they were now in business to provided relief for the sick. In California, 13 such clubs rapidly went into operation, selling marijuana openly under the guise that doing so had been legitimized at the polls. The problem was that these organizations were selling to people under the flimsiest of facades. One club went so far as to proclaim: "All use of marijuana is medical. It makes you smarter. It touches the right brain and allows you to slow down, to smell the flowers." Depending on the wording of the specific ballots, legal interpretation of what was allowed became problematic. The buyers' clubs became notorious for liberal interpretations of "prescription," "doctor's recommendation," and "medical." In California, Lucy Mae Tuck obtained a prescription for marijuana to treat hot flashes. Another citizen arrested for possession claimed he was medically entitled to his stash to treat a condition exacerbated by an ingrown toenail. Undercover police in several buyers clubs reported blatant sales to minors and adults with little attention to claims of medical need or a doctor's direction. Eventually, 10 of the 13 clubs in California were closed. Further exacerbating the confusion over smoked marijuana as medicine are doctors' concerns over medical liability. Without the Food and Drug Administration's approval, marijuana cannot become a pharmaceutical drug to be purchased at local drug stores. Nor can there be any degree of confidence that proper doses can be measured out and chemical impurities eliminated in the marijuana that is obtained. After all, we are talking about a leaf, and a burning one at that. In the meantime, the harmful effects of marijuana have been documented in greater scientific detail than any findings about the medical benefits of smoking the plant. Given the serious illnesses (for example, cancer and AIDS) of some of those who are purported to be in need of smoked marijuana for medical relief and their vulnerability to impurities and other toxic substances present in the plant, doctors are loath to risk their patients' health and their own financial well-being by prescribing it. As Dr. Peter Byeff, an oncologist at a Connecticut cancer center, points out: "If there's no mechanism for dispensing it, that doesn't help many of my patients. They're not going to go out and grow it in their backyards." Recognizing the availability of effective prescription medications to control nausea and vomiting, Byeff adds: "There's no reason to prescribe or dispense marijuana." Medical professionals recognize what marijuana-as-medicine advocates seek to obscure. The chemical makeup of any two marijuana plants can differ significantly due to minor variations in cultivation. For example, should one plant receive relative to another as little as four more hours of collective sunlight before cultivation, the two could turn out to be significantly different in chemical composition. Potency also varies according to climate and geographical origin; it can also be affected by the way in which the plant is harvested and stored. Differences can be so profound that under current medical standards, two marijuana plants could be considered completely different drugs. Prescribing unproven, unmeasured, impure burnt leaves to relieve symptoms of a wide range of ailments does not seem to be the high point of American medical practice. Illegal Because Harmful Cannabinoids found in the marijuana plant offer the potential for medical use. However, lighting the leaves of the plant on fire and smoking them amount to an impractical delivery system that involves health risks and deleterious legal consequences. There is a profound difference between an approval process that seeks to purify isolated compounds for safe and effective delivery, and legalization of smoking the raw plant material as medicine. To advocate the latter is to bypass the safety and efficacy built into America's medical system. Ballot initiatives for smoked marijuana comprise a dangerous, impractical shortcut that circumvents the drug-approval process. The resulting decriminalization of a dangerous and harmful drug turns out to be counterproductive - legally, politically, and scientifically. Advocacy for smoked marijuana has been cast in terms of relief from suffering. The Hippocratic oath that doctors take specifies that they must "first, do no harm." Clearly some people supporting medical marijuana are genuinely concerned about the sick. But violating established medical procedure does do harm, and it confounds the political, medical, and legal processes that best serve American society. In the single-minded pursuit of an extreme position that harkens back to an era of home medicine and herbal remedies, advocates for smoked marijuana as medicinal therapy not only retard legitimate scientific progress but become easy prey for less noble-minded zealots who seek to promote the acceptance and use of marijuana, an essentially harmful - and, therefore, illegal - drug. - --- MAP posted-by: Richard Lake