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Marijuana as medicine  How strong is the science?

Should marijuana be used as a medicine, as its advocates say?  Or is it a dangerous drug of abuse that exposes users to brain damage and lung cancer?

Last fall, voters in California and Arizona approved laws allowing patients to smoke marijuana for medical purposes with a doctor's recommendation.  Other states are considering similar moves.  And the influential New England Journal of Medicine has editorialized in favor of extending this policy nationwide.

Federal health and drug-enforcement officials have reacted strongly to these initiatives.  "Seeming to legalize marijuana for anything would give young people the wrong impression," says Sheryl Massaro, spokeswoman for the National Institute on Drug Abuse.  "That doesn't even seem to enter the minds of a lot of people who are promoting it for medical use."

The debate over medical marijuana seems likely to continue for some time, caught up as it is in the larger question of how the nation should deal with recreational drug use and abuse.  "It's a shame" that the debate is so polarized, says Harrison Pope, a Harvard University psychiatrist who studies marijuana.  "Science should know more about this substance by now, considering how long it has been in use."

While the debate continues, here is what is known about the health effects - both good and ill - of this controversial drug.

When it comes to the possible ill effects of chronic marijuana use, the Federal Government has willingly funded studie - and even provided government- grown marijuana.  The possible damage falls into two categories.

Effects on the brain.  Perhaps no aspect of marijuana use has been so thoroughly studied.  Researchers have established what many users know: Marijuana's effects on coordination and short-term memory make it inadvisable to drive, operate heavy machinery, or try to learn anything important while under the drug's influence.

The biochemical explanation for this may have come in 1988, when scientists found receptors for THC, a marijuana component, in the parts of the brain controlling memory, mood, visual processing, attentiveness, and the ability to filter out extraneous stimuli.  The discovery also clarified why it's impossible to take a fatal dose of marijuana: There are hardly any THC receptors in the areas of the brain that control basic life functions, such as consciousness and respiration.  As for long-term effects of pot-smoking, the results are not clear.

Researchers daily users, after several days of abstinence, continue to show subtle but measurable cognitive impairments.  But it's not clear whether this after-the-fact impairment results from changes in the brain or is just a slow, continuous release of marijuana constituents that have been stored in the brain and fatty tissues.

"Of the three studies of this question that have been done, the results show no, mild, and fairly pronounced long-term damage," says Pope.  "So the jury is still completely split."

Also uncertain is whether marijuana produces any withdrawal symptoms the way heroin, cocaine, alcohol, and nicotine do. The most that researchers have been able to discern are occasional cases of mild and short-lived anxiety and insomnia upon abrupt cessation after years of heavy use.

Respiratory damage.  For 15 years, Donald P. Tashkin and colleagues at the University of California-Los Angeles have probed the respiratory systems of hundreds of long-term, heavy marijuana smokers.  Their conclusion: Puff for puff, smoking marijuana is even harder on the lungs than smoking tobacco.

"Smokers of marijuana had as frequent symptoms of chronic bronchitis as smokers of tobacco, despite the fact that the tobacco smokers smoked more than 20 cigarettes a day, compared with the 3 to 5 joints a day used by the marijuana smokers," Tashkin says.

Marijuana smokers also had more microscopic damage to the lungs' system of defense against inhaled contaminants and microbes, as well as more precancerous cellular changes.

An analysis of marijuana smoke shows why this is so: It has 50 to 70 percent more known carcinogens than tobacco smoke.  And since marijuana joints don't have filters and are usually smoked down to the last fraction of an inch, they deliver more irritating particulates to the lungs.  Recreational users further magnify the damage by inhaling the smoke deeply and holding it in as long as possible.

But does smoking marijuana actually cause cancer?  It's too soon to tell.  "It's unusual to develop lung or upper airway cancer under the age of 40, but after 50 it occurs with increasing frequency," Tashkin points out.  "The current marijuana epidemic began in the late 1960s, and the bulk of the smokers are just now reaching the age of 50.  So we're just approaching the cusp of our ability to show an association between marijuana smoking and these cancers."  It's also unknown whether the risk of cancer would gradually decline after a person stopped smoking marijuana, as it does with tobacco.

Less is known about marijuana's beneficial side.  For the past decade, the Government has refused to provide either money or marijuana to researchers studying the drug's potential therapeutic effects, so this research has been nearly at a standstill.  Early this year, however, in response to the Arizona and California initiatives, the National Institutes of Health called together an expert panel to consider possible areas of research.  The panel concluded that there's' enough evidence of smoked marijuana's usefulness to justify resuming studies.

Researchers are interested in three major areas where smoked marijuana seems to work therapeutically:

Nausea from chemotherapy.  Because it's illegal, there are no figures available on how many cancer patients self-treat their nausea with smoked marijuana.  But a 1991 survey of more than a thousand cancer specialists found that 44 percent had recommended it to at least one patient, and that 48 percent would prescribe it if it were legal.

Before the Federal Government cracked down on research, enough had been learned to persuade the U.S. Food and Drug Administration to approve, in 1986, the marketing of dronabinol (Marinol).  This drug, in pill form, contains THC to treat nausea caused by cancer chemotherapy.

With a legal synthetic marijuana pill already available, why are people still pushing for the right to smoke marijuana for medical purposes?  Because patients and doctors assert that the two do not behave the same in the body.  And a convincing body of research, some of it now nearly two decades old, shows that smoked marijuana suppresses nausea better than Marinol pills, and with fewer side effects.

Physicians speculate that one reason for the difference is that smoked marijuana enters the bloodstream almost instantaneously, allowing patients to control their dose, whereas the oral version is absorbed slowly for some time.  In addition, there's the possibility that the complex mix of compounds in whole, smoked marijuana somehow counteracts the more unpleasant effects of pure THC, such as extreme dizziness and unsteady gait.

Some people maintain that newer antinausea medications have made both Marinol and marijuana unnecessary.

"The American Medical Association and so forth, they're not clamoring for medical marijuana, and I think for good reasons," says Billy R. Martin, professor of pharmacology at the Medical College of Virginia and a longtime researcher on the metabolism of marijuana.  "There are better drugs out there."  One often cited as such is the antinausea drug ondansetron (Zofran).

But even the newest drugs do not work for everyone - a fact that has led some patients to continue using marijuana.

AIDS wasting syndrome.  Marinol has, in limited clinical trials, proved an effective treatment for wasting syndrome, the deadly loss of appetite and consequent extreme weight loss that afflicts many AIDS victims in the end stages of the disease.  In fact, Marinol is one of only three FDA-approved treatments for this condition (the others are human growth hormone and a hormone called Megace, or megestrol acetate).

But some AIDS patients say it's not an adequate substitute for marijuana.  "All it did was make me very groggy without enhancing my appetite," one said.

AIDS activists and the doctors who treat the disease report that marijuana is also useful for suppressing the nausea that's a side effect of several effective anti AIDS drugs.

Advocates of providing AIDS patients with marijuana acknowledge the risks of the drug to lung and brain, but point out that these long-term effects matter little to someone with a terminal illness.

However, there's no firm evidence that marijuana is effective against the wasting syndrome; that has never been tested in clinical trials.  Donald I. Abrams, an AIDS specialist at the University of California-San Francisco, has been trying since 1993 to secure Government permission to compare smoked marijuana to Marinol pills.

Abrams also hopes to assess marijuana's effect on the immune system.  Many years of research have produced conflicting results, with some studies showing that marijuana depresses certain components of the immune system and others showing either no suppression or, occasionally, stimulation.  However, a long- term study of 1500 HIV-positive men who used marijuana found the drug use didn't seem to accelerate the deterioration of their immune systems.

Spasticity.  People with spinal cord injuries and multiple sclerosis are prone to painful muscle spasms and tremors; existing drugs give only partial relief, with severe side effects.

There are many anecdotal reports that smoked marijuana relieves those symptoms but, to date, no large-scale, controlled clinical trial has compared marijuana with existing legal drugs.

"With smoked marijuana, patients get immediate relief, whereas with the oral drug they get a delayed, big rush of unpleasantness.  When they take a smaller dose, it doesn't work," says Paul Consroe, a University of Arizona pharmacology professor, who is studying the effect of marijuana on muscle spasticity.

Researchers seem to have lost interest in one once-promising use of marijuana - to treat glaucoma.  They discovered early on that marijuana reduced the intraocular pressure resulting from this potentially blinding disease.  However, the treatment never caught on with more than a handful of patients; to keep pressure down, marijuana must be taken every two to four hours, and patients didn't like being high continuously.  Also, many new drugs work well, with minimal side effects.

The evidence is convincing that long-term regular use of marijuana exposes users to significant risk of lung damage; many may also suffer subtle but measurable cognitive and motor impairments that persist for weeks after use stops.  And, of course, nonmedical use of marijuana is illegal everywhere.  However, compared with other drugs of abuse such as tobacco, alcohol, and cocaine, marijuana is much less addictive - if at all - and there's no danger of death from an overdose.

A number of attempts have failed to isolate compounds from marijuana that would achieve the desired therapeutic effects without making patients high.  "It seems that the same neurological receptor controls all the effects, the good and the bad," says Consroe.

Since an unknown but probably substantial number of people are smoking marijuana with the expectation that it will help make their AIDS or terminal cancer more tolerable, CONSUMER REPORTS urges the Federal Government to permit further research in this area - to better determine the drug's efficacy and side effects.

In the meantime, CONSUMER REPORTS believes that, for patients with advanced AIDS and terminal cancer, the apparent benefits some derive from smoking marijuana outweigh any substantiated or even suspected risks.  In the same spirit the FDA uses to hasten the approval of cancer drugs, Federal laws should be relaxed in favor of states' rights to allow physicians to administer marijuana to their patients on a caring and compassionate basis.