Scientific American , September 1999

By Gary Stix

The exact location is a secret. But somewhere between London and Brighton a compound ringed by high fences and razor wire will house the world's only pot farm primarily devoted to commercial drug development. In June the British Home Office gave a startup pharmaceutical company a license to grow 20,000 marijuana plants of varied strains.

Geoffrey W. Guy, chairman of GW Pharmaceuticals, intends to proceed to clinical trials with a smokeless, whole-plant extract, while also supplying marijuana to other investigators interested in medical research and pharmaceutical development. The 43-year-old entrepreneur-physician wants to capitalize on what he sees as the unexploited opportunity to legitimize marijuana as medicine. "Cannabis has been much maligned," Guy says. "There are over 10,000 research articles written on the plant, and there's something well worth investigating here."

The idea of giving this alternative medicine a place alongside antibiotics and aspirin in the physician's standard pharmacopoeia is by no means a new one. Marijuana and its chemical constituents have aroused interest as a treatment for conditions ranging from the nausea induced by cancer drugs to the fragility of brain cells harmed by stroke. In the U.S., oral doses of delta-9-tetrahydrocannabinol (THC)--a synthetic version of the chemical in marijuana that both relieves nausea and gets a person high--have been available on the market since 1986.

But the makers of Marinol (the trade name for the THC synthetic) have had trouble competing with dealers on the street. A swallowed pill takes too long to relieve nausea. "The maximum levels of THC and the active metabolites you see after you swallow a capsule occur at anywhere from two to four hours," says Robert E. Dudley, senior vice president of Unimed Pharmaceuticals in Buffalo Grove, Ill., Marinol's manufacturer. "That's contrasted with a marijuana cigarette, where the peak levels might occur from five to 10 minutes."

Unimed and other companies are in various stages of developing nasal sprays, sublingual lozenges, vaporizers, rectal suppositories or skin patches that will deliver THC into the bloodstream quickly. But new interest in marijuana as pharmaceutical goes beyond just substitutes for smoking. Guy's motivation for establishing GW borrows a page from the herbal medicine literature. He hypothesizes that the plant's 400 chemicals, including dozens of cannabinoids such as THC, may interact with one another to produce therapeutic effects. A few studies have shown that one cannabinoid, called cannabidiol, may dampen some of THC's mind-altering effects. And synthetic THC users sometimes report feeling more anxious than smokers of the drug, perhaps because of the absence of cannabinoids other than THC.

GW Pharmaceuticals wants to test whole-plant extracts for a series of medical conditions. A Dutch company, HortaPharm, will provide seeds to GW for plants that contain mainly one cannabinoid. Different single cannabinoid plant extracts can be blended to provide the desired chemical composition.

Interest in whole-plant medicinal marijuana has even stirred in the U.S., where research on the drug has been stymied for 20 years. That bias may be shifting, as witnessed by a 1997 National Institutes of Health advisory panel that recommended more research on the subject. Robert W. Gorter, a professor at the University of California at San Francisco, has received approval from the Food and Drug Administration to perform a clinical trial on an orally administered whole-plant extract--and he is also organizing a separate investigation with patients in Germany and the Netherlands. "Various cannabinoids in the plant appear to work in a little symphony," Gorter observes.

Pushing whole marijuana as medicine is not a task for the fainthearted. Financing pharmaceutical development for a controlled substance may not come easy. "I need the right type of people as backers," Guy says. "I don't want people from Colombia turning up with suitcases full of dollar bills."

In addition, some scientists observe that evidence for cannabinoid synergies is relatively slim. "There has never been an effect of marijuana that has not been reproduced with pure delta-9-THC," says John P. Morgan, a professor of pharmacology at the City University of New York. "Herbal medicine advocates think that plants are better because there's a mix of natural substances. There's not much basis for most of these claims."

Ultimately, advocates of marijuana as natural medicine may find their work superseded by developments stemming from discoveries of cannabinoid receptors in the human body--and of molecules that bind to them. Some research groups are seeking analogues to the binding molecules naturally present in the body that might provide therapeutic benefits superior to those of plant-based cannabinoids.

Receptor research is also shedding light on the role played by the cannabinoids found in marijuana. NIH investigators reported in the Proceedings of the National Academy of Sciences in early July that THC and cannabidiol serve as powerful antioxidants. In laboratory rat nerve cells, the compounds can prevent the toxic effects of excess glutamate, which can kill brain cells after stroke. (After reading this report, legalization advocates reveled at the notion that marijuana may actually protect brain cells.)

To proponents of legalization of the smokable herb, arguments about alternatives remain academic. "Because patients are receiving full relief right now from smoking the whole plant, we shouldn't let them suffer while science plods along trying to come up with synthetic analogues that may not have the same beneficial effect," says Allen F. St. Pierre, executive director of the National Organization for the Reform of Marijuana Laws Foundation.

Some medical users would rather fight than switch from joints or brownies. Elvy Musikka, a glaucoma patient in Hollywood, Fla., is one of eight people enrolled in a federal program that supplies the drug for medical reasons. She maintains that if her legal supply is cut off she will move to a country where she can grow her own. "I think for the pharmaceutical companies to think they produce a better product than God is totally presumptuous," she says. Pharmaceutical makers may find that Musikka's attitude--shared by thousands--becomes the biggest impediment to successful drug development.