Within the next month, the federal government will begin distributing the active ingredient in marijuana to thousands of cancer victims, free of charge.
The drug distribution program, now getting under way at the National Cancer Institute, could provide the marijuana ingredient delta-9-tetrahydro-cannabinol, or THC, to several hundred thousand patients a year to combat the disabling vomiting caused by chemotherapy. For 75,000 of the patients, it may be the only thing that will work.
The plan calls forth both blessings and curses. Some cancer experts say it is an act of mercy, others a dangerous and premature surrender to political pressure.Even marijuana lobbyists are at odds, some hailing it as a long step down the road to legalization and others damning it as a sinister plot to discredit the weed.
The cancer institute's decision to distribute the drug nationally -- taken after much bureaucratic soul-searching in concert with the Food and Drug Administration and the drug enforcement branch of the Department of Justice -- represents a philosophic about-face from the government attitude five or six years ago, when federal officials made researchers sign their lives away to obtain even small supplies of THC.
Dr. Stephen Sallan, the Harvard cancer researcher who first studied the effect of marijuana and THC on vomiting, said: "As they say in Virginia Slims cigarette ads, 'You've come a long way sister.' That's what I'd say to the feds."
Government officials downplay the impact of the program and the change of heart that made it possible. "This is not really marijuana," said Dr. Edward Tocus, chief of the FDA's drug abuse branch. "This is a drug to treat a serious condition."
Many cancer patients who have tried THC as research subjects strongly favor its distribution. "I hope it is going to be available for everybody who needs it. It sure worked for me," said Anne C. Herron, a Kensington resident who received THC last month before undergoing chemotherapy at Georgetown University Hospital for a form of cancer called melanoma.
"I felt fine, and I didn't have any aftereffects with it," she said. Although Herron said she did vomit a few times after receiving her medicine, "it was very moderate. Before . . . I always threw up constantly."
Scientists say that THC is not the ideal drug. It is erratically absorbed from the intestines, and not metabolized identically by every patient. aIts psychic effects may be pleasant for young patients but frightening for older ones. It doesn't work for everyone. And to work at all, it has to work every time -- because, Sallan said, "if you vomit once or twice, you can't get the next dose down."
Nevertheless, the announcement of the cancer institute's program represents official recognition that marijuana contains at lease one ingredient that is medically valuable.As such, it may have influenced the U.S. Circuit Court of Appeals for the District of Columbia in a decision Oct. 15 to order the government to reconsider the weed's definition as a drug with no medical uses. Both marijuana and heroine currently belong to that category, called Schedule I, which contains drugs under strictest control.
The cancer institute program "is potentially a very large-scale distribution of marijuana," said Dr. Daniel Hoth, who is in charge of supervising trials of new cancer drugs. The institute is paying for the THC capsules (which cost 24 cents each to make) out of its general funds, and officials estimate the program will cost $1 million during its first year.
Hospitals will get THC capsules from the government and doctors can then order them from the hospital pharmacy for cancer patients. There are no plans to distribute the drug through retail pharmacies.
Although the institute also distributes other drugs, such as cerain chemotherapy medicines, it has never before embarked on a distribution of this scope. Hoth predicted it would be "the major revolution" in the way marijuana and its relatives are viewed -- perhaps ultimately changing them from recreational ato medical drugs.
The decision to make THC widely available stems from at least eight published studies showing that it quells the severe vomiting caused by chemotherapy drugs, Sallan said. A panel of cancer experts at the FDA studied the evidence last June and judged that THC should be distributed for humanitarian reasons, since for about one-quarter of chemotherapy patients, it appears to be the only currently available drug that works. Sallan said that in another one-quarter of the patients, vomiting can be prevented equally well by either THC or prochlorperazine, an antivomiting drug already on the market. Half the patients, he said, are not helped by either drug.
Sallan said that 600,000 Americans will learn this year that they have lung, breast or intestinal cancer, and probably at least 300,000 of them will receive chemotherapy. So if one-quarter are helped only by THC, that comes to 75,000 patients.
But there is still argument over whether the government should distribute THC, plain marijuana, both or neither. THC was originally isolated as the ingredient that seemed to have the most powerful effect on the brain, and was used for research into marijuana's possible toxic effects. It produces a "high" that may or may not be wedded to its anti-nausea properties; some patients find it pleasant but for others it can be disorienting or even dangerous.
Although most studies of THC have reached favorable conclusions, one conducted on cancer patients at the Mayo Clinic did not. Twelve of 38 patients on THC dropped out of the study because of intolerable side effects that included dizziness, inability to walk straight, hallucinations, and muddled thinking. Dr. Charles G. Moertel, director of the Mayo Comprehensive Cancer Center, said he was uncertain whether the side effects were caused by too high a drug dose, lack of previous experience with marijuana among the Mayo patients, or some difference in the way THC affects older people. The Mayo patients were in their 50s, 60s and 70s, in contrast to patients in other studies who were often younger.
Moertel opposed the FDA panel's recommendation to approve distribution of THC, and argues that the program is premature because a safe, effective dosage of the drug has not been established.
"I suspect they're yielding to political pressures to . . . do the right thing for cancer patients," he said. "With our experience, the patients were made worse with this approach, not better. This is not a kind thing to do."
But cancer and drug experts in the three government agencies involved feel that it is a kind thing to do, and that it can be done safely. For several months, Arthur D. Little Inc. in Cambridge, Mass., has been chemically synthesizing the program's first batches of THC, suspended in a sesame oil solution. According to Paul Davignon of the cancer institute, the Massachusetts firm then ships samples of the drug to the Midwest Research Institute in Missouri, which tests it to ensure purity and potency.
After it is tested, the THC is shipped to Chatsworth, Calif., where the Banner Gelatin Co. puts it into capsules. Sample capsules are again tested in Missouri. Ultimately, the pills wind up in a storage laboratory used by the National Cancer Institute at Flow General Inc. in McLean, waiting to be sent to the nation's hospitals.
Meanwhile, hospitals interested in ordering THC for their pharmacies are applying to the Justice Department's Drug Enforcement Administration. Narcotics officials check each hospital's security system to be sure supplies will be safe from theft, then register the hospital and those staff docots who plan to dispense, the drug.The hospital can then order capsules, which must be provided free to patients, except for dispensing costs. Hoth said the first orders have already arrived, and he expected the first supplies to be shipped in the new few weeks.
In 1974, Sallan and other cancer doctors first learned from patients who used marijuana that smoking before chemotherapy seemed to decrease the nausea that is one of the worst side effects of treatment. The government has gone on funding development of the drug ever since, according to the FDA's Tocus, because no drug companies have shown interest.
"A pharmaceutical company generally is a rather conservative organization," he said. "Marijuana . . . has a scuzzy kin of reputation. Not even researchers in the universities were too interested at first. They didn't want to tarnish their reputation." He added, laughing, "The federal government, of course, jumped right in."
Now according to Sallan, five or six drug companies are climbing on the bandwagon. But he said their efforts are focused on finding a relative of THC tha provides relief from vomiting without a "high," which they regard as a drawback -- especially if a drug is to be marketed not only for people hospitalized with cancer but for others who might take it while driving or working.
He said Eli Lilly and Co. sponsored research on nabilone, a chemical cousin of THC, and got results showing it prevented vomiting. But the company stopped research for a year when some laboratory dogs died of brain damage. Not, he said, the company has determined to its satisfaction that the dogs were made sick by a related chemical, not by nabilone, and is going ahead with more studies.
Sallan is testing another chemically similar drug, levo-nantradol, supplied by Pfizer Inc. Its major advantage over THC is that it can be injected. THC comes only in a pill, so it is useless for anyone who is already vomiting.
Not everyone who has pressed for marijuana's legalization or its approval for medical uses is overjoyed with the cancer institute's program. Although marijuana lobbyists see THC distribution as a step toward legalization, they argue that the institute should be passing out marijuana cigarettes as well.
Its failure to do so, said Peter Meyers, chief counsel for the National Organization for the Reform of Marijuana Laws, "is based 100 percent on prejudice [that] smoked marjuana cannot be a medication because that's what people are smoking in the streets . . . to enjoy themselves."
Robert Randall, president of the Alliance for Cannabis. Therapeutics, goes further. He calls the program a "sinister . . . attempt to undermine the status of cannibis," using a drug that is "medically inferior to marijuana." Furthermore, he said, THC "produces a lousy high."
For all the capsule's shortcomings, scientists contest Randall's statement that it is inferior to a marijuana cigarette. Although the ingredients of smoked marijuana rapidly enter the bloodstream and go directly to the brain, Sallan said the amount abosrbed from the lungs varies with how "efficiently" the patient smokes -- and some patients, especially those with lung cancer, may not be able to smoke at all.
The federal plan to distribute THC is viewed with mixed emotions in the states destined to receive it. Prodded by relatives of cancer victims, 24 state legislatures have passed laws setting up their own programs to provide marijuana or THC and the Food and Drug Administration has approved 12 state programs. But the programs depend on the federal government supplying the drugs, and Dr. Robert E. Willette of the National Institute on Drug Abuse said that so far only five or six states have actually received any.
Now, responsibility for shipping both THC capsules and marijuana cigarettes has shifted to the cancer institute, whose own program is competing with the states for government supplies. Some state officials are infuriated by the resulting delay.
Hoth said he had spent much of his time in recent weeks parceling out the government's medical marijuana. "There may be a shortage [of capsules] till early spring, when a large supply of THC will be available," he said. "Our intention . . . is to let everybody have some and get things going."
Sallan predicted that providing cancer patients with a government-produced marijuana ingredient will drastically improve the weed's public image. "Marijuana, like anything else, is evil when it's abused and beneficial when it's used right," he said. "I don't think that makes it too much different from a bottle of beer or an aspirin."