Trials Of Marijuana's Medical Potential Languish As Government Just Says No

Government Just Says No Author: Peter Gwynne Can smoking marijuana help to alleviate the loss of appetite and weight that accompany AIDS? Much as they would like to know, people with AIDS and their physicians seem unlikely to get a definitive answer to that question any time in the near future. FIELD OF DREAMS: The University of Mississippi grows marijuana for NIDA, for use in reserach that meets the institute's criteria. For more than three years, a physician proposing to undertake a pilot clinical trial on pot treatment has consistently failed to receive from the federal government the marijuana necessary to carry out the trial, or federal approval to obtain nongovernment pot for it. Researchers involved in the effort to start the experiment emphasize that nobody in government is singling out AIDS. At present, no trial for any other suggested medical use of marijuana-to treat the nausea associated with cancer chemotherapy, to lower intraocular pressure in glaucoma patients, or to relax muscles in such spastic disorders as multiple sclerosis, for example-is under way in the United States, or in any other country. Proponents of studies of pot-smoking put the blame for the lack of action squarely on the U.S. government. They charge that the Clinton administration, like its predecessors, has an irrational fear of being labeled soft on drugs if it gives the go-ahead for clinical trials of marijuana for medical purposes. "I think the administration and Congress flee from this as fast as possible," says Alvin Novick, a Yale University biology professor who is chairman of the Gay and Lesbian Medical Association's AIDS Task Force. "The federal government is saying: 'No way will we allow medical research with marijuana,'" contends Richard Doblin, a Ph.D. student at Harvard University's Kennedy School of Government who is president of the Multidisciplinary Association for Psychedelic Studies (MAPS). Based in Charlotte, N.C., MAPS is a nonprofit research and education organization that promotes investigations of what Doblin calls "mind-manifesting drugs." Government leaders appear reluctant to talk on the record about clinical trials of marijuana. Officials at the Drug Enforcement Administration (DEA) and the National Institute on Drug Abuse (NIDA) did not return repeated phone calls from The Scientist. Nevertheless, sources at these agencies, who request anonymity, disagree that they are making life difficult for researchers who aim to study potential medical benefits of marijuana. While arguing that marijuana is a dangerous drug for which no evidence of medical value has emerged so far, they say that they will approve-and NIDA will provide marijuana cigarettes for-well-designed trials of its potential clinical value. So far, they maintain, nobody has suggested an acceptable protocol. Life wasn't always so hard for marijuana researchers. "There's a long history of experiments with marijuana smoking," recalls Rees Jones, a professor of psychiatry at the University of California, San Francisco. "Many of us had million-dollar grants back in the good old days." Up to the mid-1980s, NIDA funded scores of human studies annually, many related to the clinical pharmacology of marijuana. Since 1992, Donald Abrams, a physician at the University of California, San Francisco, has sought approval for a pilot clinical trial on the possibility that smoking pot can improve the appetites of people with AIDS and hence increase their weights. He plans to carry out the trial with the sponsorship of San Francisco's Community Consortium on AIDS Research, of which he is research director. He envisions the trial as involving 40 patients, who will adhere to strict criteria. Among other requirements, they will have to be clinically diagnosed as having AIDS clinical wasting, manifested by the loss of 10 percent of body weight; have had their weight monitored over the previous two months; prove that they are not current users of marijuana; and be at least 18 years old and capable of giving informed consent. Abrams and MAPS, which has emerged as one of his major supporters, have methodically gone about obtaining official imprimaturs for the proposed line of research. The California Research Advisory Panel, the UC-San Francisco Review Board on Human Subjects, and the Food and Drug Administration (FDA) have all accepted the protocol. But Abrams and his supporters have been unable to convince NIDA to provide marijuana for the study or DEA to permit them to import it from non-U.S. government sources. "It's a very highly charged subject," Abrams tells The Scientist. A Government Grower The government has the marijuana available. On a farm in Oxford, Miss., the University of Mississippi grows marijuana to order for NIDA, which distributes it for animal and human studies that have satisfied its criteria for peer-reviewed protocols. "We grow an amount depending on the need, from nothing to 11/2 acres," reports Mahmoud Elsohly, a research professor who runs the farm. Staff at the farm ensure that the quality of the crop meets NIDA's needs by selecting the right seed stock and by special harvesting techniques. Elsohly sends his crop to the Research Triangle Institute (RTI) in Research Triangle Park, N.C., for processing. There, according to RTI communications manager Reid Maness, the marijuana leaves are stripped, cleaned, and analyzed for their content of tetrahydrocannabinol (THC), the most potent of the plant's 61 active ingredients. RTI workers make the marijuana leaves into filterless cigarettes, which they freeze and store. NIDA determines who gets the cigarettes. At present, just eight human patients receive them under official sanction; laboratory animals and smoking machines consume a much larger share of the supply. The group of eight people illustrates the way in which government policy has changed on the use of marijuana for medical purposes. In the late 1970s, in response to legislation enacted in several states, the federal government reluctantly approved a few Investigational New Drug (IND) applications; under those, physicians could prescribe marijuana cigarettes for patients with specific diseases. In the period 1989-90, the number of such "compassionate INDs" increased to 34, according to Lester Grinspoon, an associate professor of psychiatry at Harvard Medical School who is a leading proponent of the medical value of marijuana. In June 1991, however, the Public Health Service announced that it would suspend the program, owing to the government's opposition to illegal drugs. Last year, Department of Health and Human Services assistant health secretary Philip Lee decided to phase out the program altogether; he asserted the lack of persuasive research to indicate the program's value. Nevertheless, eight patients approved under the original program still receive marijuana cigarettes, through their private physicians. Some of them initially participated in studies of the drug's effect on their health; for example, they stopped smoking marijuana altogether for various periods, or occasionally substituted Marinol, an oral pill that contains synthetic THC but not other components of the marijuana plant. According to Doblin, however, other participants in the IND program had to convince federal judges that they needed to smoke marijuana on a regular basis in order to get into the program; carrying out research that kept them off marijuana cigarettes would plainly have put them on sticky legal ground. Eventually the research on the original patients was discontinued, without having provided any definitive results. "We are getting no research data whatever from the group of eight," reports Mark Kleiman, an associate professor of public policy at the Kennedy School of Government, and chairman of the Federation of American Scientists' Drug Policy Committee. For everyone in the U.S. apart from the eight, Grinspoon and law lecturer James Bakalar explained the reality in a commentary in the Journal of the American Medical Association in June (L. Grinspoon, J.B. Bakalar, JAMA, 273:1875-6, 1995). Marijuana, they wrote, "is officially a forbidden medicine." That commentary, entitled "Marijuana as Medicine: A Plea for Reconsideration," represented a significant move in the effort to obtain approval for clinical trials, in that Grinspoon was able to put forward his long-held and often-stated belief in the medical value of marijuana in a highly prestigious journal. "I know that [marijuana] is very useful for AIDS patients and that it won't hurt them," Grinspoon tells The Scientist. "I think the government's position [against clinical trials] is immoral, illegal, and certainly unscientific." The government reacted quickly to the Grinspoon-Bakalar paper. "I am very concerned about the JAMA commentary that advocates the medical use of marijuana," said DEA administrator Thomas Constantine in a statement. "Marijuana is listed as Schedule I under the federal Controlled Substances Act because it has a high potential for abuse and no currently accepted medical use. The DEA will remain opposed to the rescheduling of marijuana from Schedule I [which covers heroin, LSD, and other drugs with no established legitimate medical use] to Schedule II [which includes drugs such as cocaine that have high potential for abuse, but proven medical value] because there are no proven medical applications for its use. In fact, the American Glaucoma Society, the American Academy of Ophthalmology, the International Federation of Multiple Sclerosis Societies, and the American Cancer Society have rejected marijuana as medicine." In a statement issued in March 1993, the American Cancer Society declared that "for the most part . . . smoking marijuana is no more effective [in treating chemotherapy- induced nausea and vomiting] than taking synthetic THC by mouth. Moreover, inhaling marijuana smoke is a health hazard." UNTAPPED POT-ENTIAL: From left, Donald Abrams, has been seeking approval to test marijuana on AIDS patients since 1992; Lester Grinspoon calls the U.S. policy "immoral"; Siegfreid Streufert says obtaining approval for this marijuana protocol delayed his study. The American Academy of Ophthalmology issued its rejection in 1987 and updated it in 1992. The academy's statement declared that its "Committee on Drugs presently finds no scientifically verifiable evidence that the use of marijuana is safe and effective in the treatment of glaucoma." The statement conceded that "there is evidence that marijuana (or its components) taken orally or by inhalation can lower intraocular pressure. However," it continued, "there are no conclusive studies to date to indicate that marijuana (or its components) can safely and effectively lower intraocular pressure enough to prevent optic nerve damage." Proponents of clinical trials of pot assert that they're in a chicken-and-egg situation: To convince the federal government of the benefits of marijuana as medicine requires clinical trials; but the government insists that clinical trials are unwarranted because no solid evidence exists of pot's medical value. NIDA is funding more than 35 investigations-separate from the original INDs-that involve humans smoking pot. Several of these focus on individuals who smoke marijuana that they have obtained through their own devices, but in four grants the agency has allocated government-supplied and -approved marijuana cigarettes for human patients. Approval can consume excessive time, however, as the experience of Siegfried Streufert in Pennsylvania State University's behavioral science department illustrates. Streufert has a contract to study the effects of NIDA-supplied marijuana cigarettes, and other drugs, on simple and complex performance by human subjects. "We are just beginning this [marijuana] phase of the research," Streufert tells The Scientist, "although we anticipated doing it two to three years ago." The reason for the delay: the need for multiple approvals of the protocol. Streufert must not only obtain approval from NIDA, FDA, Penn State's Institutional Review Board, and DEA, but also renew the approvals each year. "By the time it's taken about eight months to obtain an approval, you're ready for the next round," he complains. Abrams is now preparing his application to NIH's Office of AIDS Research. It is due by January 1, with a decision from NIH expected by next May. Meanwhile, MAPS and Abrams are trying to round up marijuana for the study from approved nongovernmental sources-so far without success. One recent line of exploration, according to Abrams: obtaining the plant from confiscated supplies owned by the state of California. Some of Abrams's academic peers wonder whether it's possible to carry out a truly meaningful study of smoking pot, owing to the variables involved. "Smoking marijuana might not be useful generally because it affects too many systems in the body," muses Rees Jones, who chaired the UC-San Francisco Review Board on Human Subjects that approved Abrams's original proposed protocol. A study of that sort, he adds, "has got to be a very formidable scientific undertaking." However, debate over doubts such as Jones's could serve to improve Abrams's experimental plan. "The happy result could be a stronger protocol," says Harvard's Kleiman. Both sides agree on one potential danger of smoking pot: to the lungs. That problem is under investigation, however. A study funded by MAPS and the California branch of the National Organization for the Reform of Marijuana Laws (NORML), the lobbying group pressing for legalization of marijuana, is exploring whether water pipes and vaporizers can reduce the amount of particulate matter produced during pot smoking that finds its way into smokers' lungs. The investigation, in which machines rather than humans do the actual smoking, uses marijuana supplied by NIDA. The U.S. is not alone in lacking controlled human studies of the potential medical benefits of marijuana. "There are lots of countries where the drug situation is taken less seriously than here-Canada, the Netherlands, Britain, parts of Germany, and Switzerland," Kleiman points out. Nonetheless, "in none of those countries is there any cannabis research that I can discover." Why? "One possibility is prejudice against herbal medicine," suggests Kleiman. "Pharmaceutical companies and physicians and regulators all believe that white powders that are pure chemical species are good, while pieces of plants are folk medicine, and they don't want to be in folk medicine." Certainly, Kleiman concedes, one marijuana plant varies from the next. Even if a clonal form existed, he adds, researchers would find variability among the interactions of a dozen components and the reproducibility of inhalation. Despite that, he notes the irony that Marinol pills, which consist of 100 percent THC, "are noncontroversial, while anything less than 100 percent THC is controversial." Physicians prescribe Marinol mainly for reducing the pain of patients undergoing cancer chemotherapy. Yale's Alvin Novick adds one more irony of the present situation: "Almost anyone in this country can get marijuana if they want it." In other words, anecdotal evidence of its benefits abounds while measured scientific readings are impossible to obtain. However, Richard Doblin adds a rider to that point. Individuals risk arrest even if they obtain their pot for medical relief. Nobody expects a simple resolution of the question of Donald Abrams's proposed study. "Everything about marijuana seems to get very politicized," says Rees Jones. "Combine it with AIDS Peter Gwynne is a freelance science writer based in Marstons Mills, Mass.

Trials Of Marijuana's Medical Potential Languish As Government Just Says No

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