A MEDICINAL HERB? NIH may soon be looking into the therapeutic effects of marijuana as consensus grows among scientists that such studies are worth doing.
There is a rationale for looking further into the therapeutic effects of marijuana, stated panel chairman William Beaver, a professor of pharmacology at Georgetown University, at a news conference after an NIH-sponsored "Workshop on the Medical Utility of Marijuana," held in February. "For at least some of the potential indications, we feel that it looks promising enough to recommend that there would be some new controlled studies done."
The federal government, as a matter of policy, has refused to permit any clinical studies of the drug's potential curative effects. Under the Controlled Substances Act, Title II of the Comprehensive Drug Abuse Control Act of 1970, marijuana is a Schedule I drug. Such substances are defined as having a high potential for abuse and no currently accepted medical use in the United States. Schedule II drugs have a high potential for abuse but also have an accepted medical use with severe restrictions.
UP TO SCRUTINY? Proposals for studying marijuana would be funded if they passed standard evaluations, says NIDA’s Alan Leshner.
Some scientists wonder whether supporters of clinical trials on marijuana are protesting too much about their inability to obtain federal funds to conduct such studies. "There's never been a ban on marijuana research of any kind," says Reese Jones, a professor of psychiatry at the University of California, San Francisco, and a longtime marijuana researcher who spoke at the NIH workshop. Jones argues that the research community is partially responsible for the present dearth of clinical studies on marijuana's therapeutic effects. "There's a fair amount of red tape associated with any Schedule I drug. Rather than jumping through all the hoops, scientists will, other things
TOO MUCH TOUTING: Virginia Commonwealth University’s Billy Martin charges the marijuana lobby with overstating the drug’s healing power.
The advocacy has been far from one-sided. On December 30, less than two months after the medical marijuana initiatives passed in California and Arizona, the federal government threatened to take action, possibly including prosecution, against doctors who prescribe marijuana. That same day, drug czar Barry McCaffrey appeared in a CNN news report on the issue. When asked if marijuana has medicinal value, he answered: "No, none at all. There are hundreds of studies that indicate that it isn't." (Shortly after that, the government announced that it was giving $1 million to the Institute of Medicine for an 18-month study to assess the drug's medicinal value.) The Internal Revenue Service weighed in with an announcement that taxpayers would not be able to claim use of marijuana as a medical deduction.
The passage of the two initiatives and the federal government's reaction to them have shown how wide a gulf exists between supporters and opponents of medical marijuana. "People in California and Arizona think that they have a right to medical marijuana; patients go to the street or to buyers' clubs to get their joints," argues Kevin Zeese, a lawyer who is president of the Washington, D.C.-based organization Common Sense for Drug Policy. "If your real concern is that you don't want kids and non-patients to get marijuana, the best way is to make marijuana a Schedule II drug-sold only on prescription with controls."
The NIH panel represents an effort to disentangle those two concerns. So far, no panel member is talking about the likely recommendations. But supporters of expanded use of medical marijuana remain suspicious. "My guess is that [the panel's] recommendations will be kind of narrow," says Paul Consroe, a professor of pharmacology and toxicology at the University of Arizona Health Sciences Center, who spoke at the NIH workshop. He expects recommendations for studies to apply to limited groups of patients and, as a result, forecasts that few research groups will submit proposals.
Investigating marijuana's therapeutic powers involves more than Washington politics. Both opponents and supporters agree that exploring the medical effects of marijuana presents a complex-and costly-scientific challenge. For example, because measuring precise doses of a smoked substances is difficult, "designing studies of marijuana is a scientific roadblock," argues Consroe. Established protocols for research on orally administered drugs don't apply to an intoxicating substance of inconsistent purity that is smoked. Investigators must deal with the difficulties of measuring doses and developing believable placebos.
BURNING QUESTION: FDA’s Robert Temple says researchers will have to show that smoked marijuana has real advantages over alternatives.
One drug related to marijuana is already on the market: Marinol, a pill containing delta-9-tetrahydrocannabinol (THC), marijuana's main active ingredient. Produced by the Roxanne division of Boehringer Ingelheim, based in Ridgefield, Conn., Marinol is very expensive: about $500 for 100 10-mg capsules. It's also difficult for nauseous patients to consume, notes Martin.
Proponents and opponents of medical marijuana research agree that any studies should focus on patients who don't respond to traditional medications-particularly those in chronic pain or in the final stages of terminal illness. "When you're evaluating terminal AIDS patients, the standards change. You can be much more flexible," asserts Martin. He adds, however, that "there's the danger of sowing false hopes."
Researchers strike other cautionary notes about marijuana's medical value. Discussing anecdotal evidence of marijuana's effect on glaucoma at the NIH workshop, University of Wisconsin glaucoma researcher Paul Kaufman noted that "I have absolutely no idea how this drug works as a treatment for glaucoma." Jones points out that half a dozen good medications exist for glaucoma pressure. "Should there be a major effort because a small group of patients feels that traditional medications don't work well enough?" he asks rhetorically.
The problems of studying marijuana extend beyond traditional perceptions of what medications should look like. Most disturbing is the issue of finding a realistic placebo. Many experienced users quickly realize that they are smoking marijuana cigarettes without THC; the cigarettes burn faster and hotter, and the users don't get the expected high. "There's no way you're going to fool them for any length of time," contends Beaver.
In addition, smoking marijuana exposes study volunteers to risks similar to that from tobacco smoking, a sensitive issue for ethical researchers. "This is a scientific difficulty," acknowledges Marie-Eileen Oneil, a health policy coordinator at the Massachusetts Department of Health.
Temple focused on another potential problem for new studies in his talk at the NIH workshop. "Smoked marijuana will need to show some real advantage over alternatives," he said. "Showing superiority over existing therapy is very hard."
Setting up protocols is difficult in itself. Research teams are working on several possibilities. One is a so-called double dummy study, which would give subjects both marijuana and placebo cigarettes, and Marinol and placebo pills, to ensure that they received THC in one form or another. Some groups with an eye on the future are examining the possibilities of incorporating THC into aerosols like those that deliver medications to asthmatics and developing a non-burnable form of marijuana.
Another possibility is to provide patients with marijuana cigarettes of different strengths. That may reveal potential side effects as well as possible medical value. Some years ago in a study on orally administered THC, recalls Beaver, a doubling of the dose caused much better analgesia, but it also caused serious loss of control of patients' thinking. "Some patients thought they were dying," he says. "When they had fantasies, they were not nice fantasies."
HINDERED BY BUREAUCRACY: Arizona’s Paul Consroe says the amount of red tape involved in marijuana research discourages scientists.
| The National Institutes of Health's "Workshop on the Medical Utility of Marijuana," held February 19 and 20, served as a forum for researchers to present data on the therapeutic uses of the drug to an eight-member panel of scientists. The panel's recommendations may help determine future funding of studies to assess marijuana's possible healing powers. |
Panel members, who represent a broad spectrum of medical researchers, are:
William T. Beaver, a professor of pharmacology and anesthesia at Georgetown University School of Medicine (chairman);
The presentations at the February workshop were designed to help panelists answer four questions: What research has been done on possible medical uses of marijuana; what are the major scientific questions yet to be answered; what are the diseases or conditions for which marijuana might have potential as a treatment and that merit further study; and what special issues have to be considered in conducting clinical trials of the therapeutic uses of marijuana? The panel will adhere strictly to those questions and ignore background issues such as legalizing marijuana for social use. "We're going to stay strictly on the medical side of this," says Beaver.
Individual panelists will send their answers to those questions to the National Institute on Drug Abuse. There, an independent psychopharmacologist will compile the information and send it to the panelists. "We will read it, make appropriate changes, and communicate among ourselves to get a consensual reading or differences of opinion," says Beaver. "We had very little time to actually talk to each other [at the workshop]. That talking will have to take place after the fact."
Beaver doesn't expect the panel to send its answers to those questions to NIH director Harold Varmus until late April. Varmus, however, is under no obligation to take action on the basis of the panel's report.
Another effort to assess marijuana's medicinal value has yet to get under way. White House drug czar Barry McCaffrey announced on January 7 that he had contracted with the Institute of Medicine (IoM) for a $1 million evaluation "intended to provide a comprehensive assessment of scientific knowledge and to identify gaps in the knowledge base about marijuana."
At present, the study is in limbo, in the middle of a mandated period during which other institutions can put in bids to carry out the study. While nobody expects IoM to be shut out of the deal, no formal contract had been signed at press time. Once the signing takes place, IoM will appoint panel members, who then will have 18 months to carry out their task.
In response, Oneil's team is developing research protocols for patients suffering glaucoma or nausea from chemotherapy who have not responded to conventional treatments. The group plans to submit its protocol to FDA next month. The researchers have written to Health and Social Services Secretary Donna Shalala (with copies to the Massachusetts congressional delegation) outlining their approach and asking her to consider the proposal seriously. "We're making sure there's no sense of impropriety," declares Oneil. "We are pursuing it with the belief that it will be approved."
Donald Abrams, assistant director of the AIDS program at San Francisco General Hospital, is the single scientist who has presented a research proposal in recent years. Since 1992 he has sought approval for a pilot study on the value of smoking marijuana in improving the appetites of AIDS patients, but the government has consistently refused to supply marijuana for his work (P. Gwynne, The Scientist, Nov. 27, 1995, page 1). Now, Abrams is working on a new protocol for AIDS patients with wasting disease. It involves two strains of marijuana and active or placebo Marinol, he tells The Scientist.
Consroe is more circumspect. "I'm starting to look at this just in case we can get something going," he says. The reason: "There has been so much red tape involved. Why should I spend five years of my life sending in forms and answering questions when I know it won't be approved and I won't get the money?"
Peter Gwynne is a freelance science writer based in Marstons Mills, Mass.