In addition to this Fast Company feature, Bill Breen also contribtes several Web Exclusives -- related articles that did not run in the magazine. Hortapharm CEO David Watson discusses  what might be the world's largest cannabis-seed library. Rick Doblin suggests  a solution to NIDA's ailing medical-marijuana program. And Lester Grinspoon argues  that cannabis should not be "pharmaceuticalized." Learn more about the Aboveground Marijuana Economy -- all on fastcompany.com
One night in late September, Ethan Russo stood before a classroom packed with students on the University of Massachusetts' Amherst campus, and asked how many of them had been through the popular secondary-school program known as Drug Abuse Resistance Education, or DARE. Almost every hand in the audience went up. "Just as I thought," said Russo. "Well, we're going to hit that one head-on." He then cheerfully presented his version of what can only be described as a drug reeducation program.
Russo is a physician specializing in child neurology and one of the world's pioneering investigators into the therapeutic uses of pot. A slight, preternaturally good-humored man, Russo exhibited an outsized knowledge of his subject. Sticking strictly to the botanical name, Cannabis sativa, he noted that the plant's effects on the mind and body were first recorded by the ancient Assyrians in 2200 BC. These days, cannabis is used, mostly illegally, to relieve the nausea that accompanies chemotherapy, stimulate the appetites of AIDS sufferers, prevent blindness induced by glaucoma, suppress migraine headaches, and reduce the pain and muscle rigidity that accompanies multiple sclerosis.
Although nonprescription medications such as aspirin kill thousands of people every year, not a single death has ever been attributed to a cannabis overdose. The "therapeutic ratio" of marijuana is estimated to fall somewhere between 20,000 and 40,000--meaning it would take that many times a normal dose to kill you. If the drug is delivered as a pill or a spray (smoking just about anything is bad for you, after all), then Russo is unequivocal: "Cannabis is a safer medicine than almost all of the standard pharmaceuticals available today."
As he spoke, Russo clicked through a dazzling slide show: verdant fields of cannabis covering the foothills of Morocco's Rif Mountains; Thailand's marijuana plants on steroids, taller than a NBA center. But the most compelling slide was of a homely, quart-sized bottle labeled "Cannabis Tincture," which seemed to symbolize this country's inconsistent attitude toward medical marijuana. The United States has at times embraced the cannabis plant and its products: From the mid-19th century up until the mid-20th century, cannabis was a mainstream medicine, listed in the U.S. pharmacopoeia. The company that marketed the bottle of tincture was none other than Eli Lilly, the $11 billion behemoth that today is best known for another mood-altering drug, Prozac.
More recently, of course, the U.S. government has cast cannabis as a pariah drug. This past June, Karen Tandy, the first woman to head the Drug Enforcement Administration, declared that marijuana "has not been shown to have medical benefits."
Ethan Russo and a small group of trailblazing doctors, scientists, and businesspeople hope to prove her wrong. Russo recently signed on as a senior medical adviser to GW Pharmaceuticals, a British biotechnology company that has conducted clinical trials of cannabis-based medicines on people suffering from multiple sclerosis and chronic pain. In a memorandum to the House of Lords' committee on science and technology, GW reported that a vast major- ity of its patients have indicated "significant alleviation" of at least one symptom, including pain, spasticity, and bladder problems; in some cases, it said, the improvement "has been sufficient to transform lives."
This past May, GW inked a deal with the German pharmaceutical company Bayer Healthcare AG to market Sativex, a cannabis-laced oral spray that's used for treating severe neuropathic pain and multiple-sclerosis symptoms. Bayer, which agreed to market Sativex in the UK and Canada--and optioned rights for Europe--is betting that in the next few months, the first modern medicine made entirely of cannabis will pass muster with British regulators. GW estimates that the European market for Sativex could total $300 million to $400 million. "We're finding that cannabis medicines have enormous pharmacological capabilities and a unique capacity to attack, in a disease like MS, an entire range of symptoms," says Dr. Geoffrey Guy, GW's founder and chairman. "If it wasn't called marijuana, by now there would have been an entire biotech industry built around this plant."
GW's breakthroughs have put Guy in the vanguard of the aboveground marijuana economy, a handful of pharmaceutical entrepreneurs who are racing to build a legal market for cannabis medicines in countries that accept the drug's therapeutic potential (read: Canada, New Zealand, Australia, and most of western Europe). If Guy's bet pays off, GW just might become the Eli Lilly of medical marijuana.
"Cruel Hoax" or Solid Science?
The push to develop plant-based and synthetic cannabinoid medicines has been building since the early 1990s, when researchers identified nerve receptors in the brain that are stimulated by marijuana's active ingredient, THC, as well as the natural body chemical that binds to those receptors. The discovery of an entirely new class of brain receptors and the neurotransmitters that act on them--the endocannabinoid system--proved to be an astounding development, opening a whole new area of therapeutics. Investigators believe that the system plays a critical role in mediating pain, appetite, movement, and memory. The giants of the drug industry, including Lilly, Merck, Pfizer, and Schering-Plough, are now hard at work in the lab, attempting to cook up synthetic versions of the 61 cannabinoid compounds found in marijuana plants. These are complex molecules with 21 carbons unique to cannabis, of which THC is the best known. Big Pharma has high hopes for these synthetics for the treatment of obesity, smoking, cancer pain, migraines, and MS symptoms. But such efforts are still in the early stages of development.
Investigators believe that the system in the brain that is stimulated by marijuana also plays a critical role in mediating pain, appetite, movement, and memory.
At the more controversial end of the aboveground marijuana economy, developers are using the plant itself instead of synthetic compounds. "At least in the near future, it seems extremely unlikely that one of these companies will come up with a single synthetic agent that's as widely applicable as a cannabis-based medicine," says Russo. GW is taking whole extracts from the marijuana plant and recombining them to produce drugs that treat specific ailments. This plant-based approach has enabled the company to develop and test Sativex in five years, at a price tag of about $60 million. It's a remarkable feat, considering that Big Pharma on average shells out $800 million on a new drug and can easily devote a decade or more to animal research and first-dose-in-man testing. GW did minimal animal testing, taking Sativex rapidly to controlled, double-blind human trials. "Something like 400 million people a year take cannabis in one form or another, and yet there's never been a recorded fatality from it," says Guy.
But you won't find any commercial development of plant-based marijuana medicines being pursued in the United States. Andrea Barthwell, a deputy director in the White House Office of National Drug Control Policy and President Bush's point person on medical marijuana, says cannabis medicines aren't compatible with modern science. They do not constitute "a serious line of research," she says.
"The people who are advancing marijuana as a medicine are perpetuating a cruel hoax that exploits our compassion for the sick," Barthwell says. "They are using patients' pain and suffering in an attempt to change America's drug control policy. Marijuana is a crude plant product that most definitely is not a medicine."
It's a curious statement, given that it seems to reflect neither the views of the international scientific community nor those of the government's own regulatory agencies. For one thing, the Food and Drug Administration is reviewing 139 new-drug applications involving botanical research products, so plant-based medicines certainly aren't anathema. As for cannabis, in 1999 the Institute of Medicine, working at the behest of the White House drug czar's office, issued a lengthy report that assessed the scientific evidence concerning potential medical uses of marijuana. Its preeminent recommendation: "Research should continue into physiological effects of synthetic and plant-derived cannabinoids."
Barthwell, however, says that marijuana hasn't been standardized for pharmaceutical production. Nor is there any evidence, she says, that the plant's various compounds can be reliably produced in consistent concentrations. Clearly, she hasn't visited the world's most futuristic pot farm.
Down on the Farm
At a secret location in southeastern England, GW Pharmaceuticals has built what might well be the most high-tech pot palace on the planet. Surrounded by electrified razor wire, video cameras, and motion detectors, the greenhouse sprawls across more than an acre of land. At any one time, more than 15,000 marijuana plants are growing under its 14-foot ceiling, with its banks of lights. Inside is a sea of green, comprised of some of the world's most potent strains of pot: Hindu Kush, White Widow, Skunk, Northern Lights. Outside of the Netherlands, GW is the only commercial organization in Europe licensed to cultivate cannabis on this scale.
GW's drug-development strategy is based on the belief that various components of the plant work to treat specific illnesses, and it is breeding plant strains in which different cannabinoids predominate. In addition to its THC variety, GW is cultivating a strain that consists almost entirely of cannabidiol, or CBD, which moderates the THC high and possesses no psychoactive effect of its own. CBD may be useful in treating neuropathic pain, inflammation, and central-nervous system conditions such as epilepsy. To date, three drugs have been tested in clinical trials: GW's high-THC variety, high-CBD, and Sativex, which is a 50-50 mix of the two.
Geoffrey Guy's goal--to cultivate medical-grade pharmaceutical plants that produce a specific cannabinoid--has required him to raise the art of cannabis-breeding to a spectacular level. Guy's CBD-producing plant strain is unique. And every one of Guy's plants--whether it's a THC, CBD, or one of several other varieties--is completely uniform, with absolutely no genetic variation between each plant. In that respect, the greenhouse resembles a living factory, where the product takes exactly 14 weeks, from planting to harvest, to move down the assembly line.
"Our job is to find out, ahead of everyone else, what the cannabinoids do," says Guy. "To accomplish that, we grow into the plant the exact profile of the chemicals we want. We control our finished product by controlling the plant."
Dressed Better Than a Banker
Geoffrey Guy is a physician and a maverick entrepreneur who has previously launched two publicly traded pharmaceutical companies. On one day in his office in a high-security compound south of London, he was decked out in a double-breasted business suit, complete with a white handkerchief peeking above the breast pocket--people in the legal-cannabis business tend to dress better than bankers. Guy cracks that his favorite mind-altering drug is rugby. He claims never to have smoked anything, least of all pot: "I've brought 14 different drugs to market, and I've never taken any of those, either."
Guy might be the only man in England who has the know-how and the political connections necessary to launch a cannabis-based pharmaceutical company and shepherd its products through the British regulatory system. Nineteen years ago, he founded Ethical Holdings, a pharmaceutical company that developed morphine products, which gave him real-world experience in winning controlled-drug licenses from Britain's Home Office. In 1990, he founded Phytopharm, a company that specialized in developing medicines from Chinese herbal remedies.
Starting in the mid-1990s, patient groups in the UK--particularly the powerful Multiple Sclerosis Society--began lobbying for changes in the drug laws that would allow sick people to receive prescribed cannabis. Guy, who had been devouring the medical literature on marijuana, thought that if he could get dispensation from the government, he had the science-and-business wherewithal to develop an approved medicine from an illegal plant. His hunch paid off. In June of 1998, after months of meetings with Guy, the British government granted GW the license to cultivate and supply cannabis for research and drug development.
Still, had Guy failed to come up with an alternative to smoking cannabis, regulators never would have allowed him to proceed. For Sativex, GW has devised a delivery device that looks like a breath spritzer: Patients spray the drug onto the lining of the mouth; it takes effect within 20 to 45 minutes. The device allows patients to determine how many doses they need to relieve their symptoms. They tend to settle out at relatively modest levels--on average, 8 to 10 sprays of Sativex a day--which appear to be enough to relieve their symptoms without incurring an intoxicating effect. "These people are suffering from a terribly debilitating disease," says Guy. "They're just looking for a safe, efficacious medicine that will help them get on with their lives."
For the U.S., a Missed Market?
While the United Kingdom seems to be on the verge of approving Sativex--and countries from Canada to Australia are permitting the compassionate use of marijuana for seriously ill people--medical marijuana research remains mired in politics in the United States. California has established the Center for Medicinal Cannabis Research at the University of California at San Diego, and the National Institute on Drug Abuse has implemented a mechanism for supplying marijuana to the center's investigators. (Scientists outside of California who aspire to investigate medical marijuana face a torturous regulatory approval process.) Thus far, federal regulators have approved 14 of the center's studies. One such study is investigating the short-term effects of cannabis on spasticity in 30 MS patients. Meanwhile, GW has just completed phase III clinical trials on more than 1,000 patients--the largest program of clinical research on cannabis ever.
In September, a California physician who had just returned from a two-day conference of the International Association of Cannabis as Medicine at Germany's University of Cologne--which brought together the world's best minds in the field--bemoaned this country's stunted research environment. "It is frustrating to watch the advancements in research on cannabis and cannabinoids taking place that we here in the USA can only dream of," he wrote in a well-circulated email. "The dark ages of medicine and science imposed by the American disease, prohibitionism, is painfully apparent."
If Geoffrey Guy realizes his dream, Sativex will simply be the first of many such drugs to sweep through Europe and Canada. Meanwhile, the politics of pot insure that cannabis-based medicines will remain out of reach for U.S. patients and the U.S. pharmaceutical industry alike.
Bill Breen is a Fast Company senior writer. He did no product sampling in reporting this story.