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N E W   S C I E N T I S T     15 March, 1997


Turn on, tune in, get well

Marijuana as medicine? Tough-on-drugs America is finally coming round to the idea that the evil weed might do some patients a power of good. —Kurt Kleiner, Washington DC

IF you're old enough to remember peace and love and bell-bottoms, then America's latest debate on marijuana will have a familiar ring to it. What's new is that the government might be coming—somewhat reluctantly—to the conclusion that marijuana could make good medicine.

Last month, at the request of the US National Institutes of Health, a group of experts spent two days reviewing all the evidence. After scrutinising the few scientific studies that have been done, and listening to doctors and their patients who say they have benefited from the drug, the panel concluded that marijuana could be useful for treating glaucoma, nausea brought on by chemotherapy, AlDS-related wasting, and the symptoms of other diseases.

The debate about the healthy and harmful effects of marijuana has rumbled on for years, but in the US it intensified in November when voters in Arizona and California approved controversial measures that would allow people to smoke marijuana legally on their doctor's orders. The federal government's response was to remind doctors that prescribing pot was still illegal under federal law and that any who do risk losing their medical licence and perhaps a spell in prison.

Anecdotal evidence

Faced with the controversy, Harold Varmus, head of the NIH, called for a workshop to examine the evidence. While the expert panel's conclusions have no official force, they are a victory for advocates of the drug, who see them as ammunition against the official government line that marijuana has no medicinal uses. On the other hand, the panel did not explicitly endorse the drug. Instead, it recommended that more research should be carried out.

"The major problem here is getting good scientific data," says William Beaver, a pharmacologist at Georgetown University in Washington DC and chairman of the workshop panel. "You can argue policy and politics all you want, but if you haven't got the data then the politics make no sense. For at least some of the potential indications, the data are good enough to recommend that new controlled studies be done."

There is no shortage of anecdotal evidence for the weed's therapeutic powers. The panel heard from people who said marijuana had helped their glaucoma, prevented nausea and eased painful muscle spasms associated with multiple sclerosis. But properly controlled studies to confirm any of these claims are few and far between. There was a brief flurry of research in the 1970s, when society seemed to be growing more tolerant towards the drug, but that ended with the election of President Reagan in 1980 and the return to a get-tough policy on drugs of all kinds.

One of marijuana's better known side effects—as an appetite booster—has increased the pressure to legalise the drug

for medical use. Many AIDS patients battling the deadly wasting that can be caused by the disease smoke marijuana to stimulate their appetites. This has made the drug a cause celèbre for America's powerful and well-organised AIDS activists.

"There is a clear consensus that marijuana has a positive effect on appetite," says Richard Mattes, professor of nutrition at Purdue University in Indiana. But it is uncertain whether a healthier appetite actually leads to weight gain: after a sudden increase in food intake, the body may simply compensate by dulling the appetite when the drug's effects wear off. Studies of

small groups of patients have shown that they do gain some weight but they do not specify whether it was useful weight in the form of lean body mass such as muscle.

There are also question marks over how helpful marijuana is at preventing nausea. Studies in the 1970s showed that the drug clearly does have antiemetic effects says Richard Gralla director of the Ochsner Cancer Institute in New Orleans. But the effect seems to be weak compared with recently developed drugs which work well for most chemotherapy patients.

Even with these drugs there may still be a place for marijuana. However good a drug there are always some people who do not respond to it and for them smoking marijuana might help. The same argument applies for patients with glaucoma a blinding disease caused by too much pressure inside the eye.

The original enthusiasm for marijuana as a glaucoma treatment dates back to the 1970s before a number of effective drugs came onto the market says Paul Kaufman professor of ophthalmology at the University of Wisconsin. But in this case he says those few studies that have been done suggest that marijuana might be just as effective as the newer drugs and again could help those for whom these new treatments don t work.

Marijuana might also bring relief to patients suffering muscle spasms associated with multiple sclerosis Huntington's disease and Tourette's syndrome. In one small study five patients with MS showed mild to moderate improvement says Paul Consroe a pharmacologist at the University of Arizona.

Conducting the necessary trials of marijuana is likely to prove difficult for both political and medical reasons. Simply setting up a trial that tests marijuana against a placebo is a challenge. Patients are not supposed to know whether they are receiving the drug or a placebo and it will be hard to produce a dummy drug that fools anyone who has ever tried marijuana.

Testing a drug that is smoked also causes problems. Therapeutically administering the drug this way has advantages: the drug reaches the bloodstream almost immediately. Smoking also allows patients to regulate their dose themselves by controlling the size of each puff and how long they hold it in the lungs. But this is not accurate enough for a controlled study that aims to find out the precise effect of a specific dose.

On the other hand efforts to deliver the drug in the form of a pill have not always been satisfactory. The main psychoactive ingredient in marijuana is delta-9-tetrahydrocannabinol (THC) which is legally available in capsule form. But THC given this way takes longer to reach the bloodstream and with fixed amounts in a capsule it doesn't allow the patient to adjust the dose so precisely. Some patients prefer the smoked version because they can stop as soon as they begin to feel its benefits but before they feel stoned something that is often impossible with capsules.

Psychoactive mix

It is also possible that delta-9-THC is not the only chemical in marijuana that contributes to the medicinal effect. Although THC is the major psychoactive compound in marijuana the plant contains some 460 other compounds including 60 other chemically related cannabinoids.

But the real problem marijuana researchers face is a political one. The pro-marijuana lobby claims that the National Institute on Drug Abuse has been unwilling to fund studies into the therapeutic effects of marijuana because it undermines its message that pot is bad for you.

The NIDA is also the only legal source of marijuana for medical studies and anyone wanting supplies must have the agency's approval. Donald Abrams of the University of California San Francisco has tried for almost five years to win approval to study the drug s effect on AIDS wasting.

Abrams s university review committee and the Food and Drug Administration approved his study. But when he tried to acquire the drug the NIDA turned him down. Abrams says that the NIDA judged the study by harsher standards than normal. I just think everybody has a political agenda. It s hard to retain scientific objectivity he says.

As its name suggests the NIDA sees marijuana mostly in terms of its potential for abuse and many observers claim this colours its judgment on which studies should be done. The NIDA will only fund research that tries to show the harmful effects of the drug says Rick Doblin a spokesman for the Multidisciplinary Association for Psychedelic Studies a pressure group in North Carolina.

In 1993 the agency redoubled its efforts to educate the public about the perils of pot when figures showed that more young people were taking it up after a long period when it seemed to have fallen out of favour. In a single year from 1994 to 1995 the proportion of teenagers smoking marijuana rose from 6 per cent to 8-2 per cent. And the average age at which people first try the drug has fallen from 18.8 in 1987 to 16.3 today.

"Our teenage drug problem is for the most part a marijuana problem—and we have a generation of children who are using marijuana earlier and earlier and are more and more likely to be armed with the dangerous misconception that it will do them no harm," says Donna Shalala the US Secretary of Health.

According to the NIDA a number of animal and human studies show that smoking marijuana can have a range of ill effects including impairment of memory brain damage lung cancer and damage to the immune system and can lead to harder drugs.

The NIDA also disapproves of the idea of dispensing a drug in a cigarette. The panel suggested that a smokeless inhaler that heated the drug and vaporised its ingredients without creating smoke might solve this problem.

Political problems aside John Morgan medical professor at the City University of New York believes there is so much evidence that the drug is safe that it could take as little as three months to approve marijuana as a prescription drug. With so much existing research showing the relative safety of pot it is time to move straight to trials of the drug s effectiveness he says.

As far as the FDA is concerned any drug—and that includes marijuana—only has to be shown to be safe and effective says Robert Temple, the agency's associate director for medical policy. It does not have to be shown to be better than existing drugs. But realistically for marijuana to make it onto the market its proponents are going to have to show it is not only as good as existing drugs but better says Temple. Smoked marijuana will need to show it has advantages to overcome the opposition of the sceptics. Showing superiority is not normally a requirement. It s hard to prove.


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