Preparing the ground for a promising medicine

Preparing the ground for a promising medicine

Bronwyn Chester | The testing, regulation and production of any medication is a long process. But when the medication happens to be an illegal substance, as in the case of one Cannabis sativa, aka marijuana, there are delays that go beyond the scientific investigation. Criminal responsibility and political reticence from government funding agencies enter the equation. But that hasn't deterred Mark Ware.

	Dr. Mark Ware PHOTO: Owen Egan

He's a patient man with a historical perspective on the subject, one he's been studying ever since his interest in the medical uses of marijuana was tweaked while working as a physician in Jamaica attending to patients suffering from sickle cell anemia. "The pain caused by the disease is severe enough to require opiates, such as morphine, but many of my patients found that marijuana prevented the onset of acute pain," says Ware, sitting in his cubbyhole of an office in the Montreal General Hospital where, for the past year and a half, he's been a research associate in the McGill Pain Centre.

It wasn't the first time Ware has seen the herb used medicinally. In fact, he suspects that as a child growing up in Jamaica, he was given a "ganja tea" by his nanny to relieve a fever. "The roots, bark and leaves of the plant are commonly used in Jamaica," says Ware, who did his medical training on the Caribbean island.

As a result of his experience with sickle cell anemia, Ware returned to his native England to review the literature on cannabis and devise a clinical trial of the drug on the disease. That formed the basis of his MSc thesis in epidemiology at the London School of Hygiene and Tropical Medicine. "I saw that there was a huge vacuum in the research," he says.

In 1999, with his thesis under his arm, Ware began looking for places to put his trial into practice. His colleagues in Jamaica hesitated to accept Ware's proposal out of fear of recriminations from their main source of funding, the U.S. National Institutes of Health.

Jamaica's loss, however, may be Canada's -- and McGill's -- gain.

Ware then applied to the McGill University Health Centre, partly because of the University's reputation in pain research, partly because Allan Rock, minister of health, had just announced that his ministry was prepared to fund studies on the medicinal uses of cannabis, and partly because he and his wife were interested in returning to Montreal, her hometown.

As providence would have it, the timing couldn't have been better. As the pain centre's director, Anneli Vainio, recounted, "At the same time as Health Canada announced it would make available $1.5 million per year over five years for research in the field, the animal data came out showing that cannabis receptors in the brain are in the same places as the pain pathways in animals."

That, combined with "the person [Ware] whose education and goals fit well with the pain centre," made for a "happy coincidence," said Vainio, adding a qualitative "if it works."

The "if," of course, has to do with funding. Now, having submitted his third proposal -- which is "watertight," in Vainio's estimation -- to the Canadian Institutes for Health Research, Ware expects a response in June. In the meantime, he has no time to twiddle his thumbs nor get discouraged.

"Now, I'm trying to understand and manage chronic pain, as well as raise awareness among my colleagues in anesthesia and in the McGill community," he says. "It's just a plant, so let's be clinical about it. If it's ever going to be on a pharmacy shelf, it has to go through the clinical trial and regulatory process."

As a member of a multidisciplinary team concerned with chronic pain, involving pain specialist Gary Bennett, psychologist Ann Gamsa, epidemiologists Stan Shapiro and Jean-Paul Collet, as well as Vainio, Ware assesses people suffering from "pain that just won't go away." He sees patients suffering "phantom limb pain," the pain in a limb that's been amputated; post-trauma pain, often the result of a car accident which afflicts the neck or lower back; and chronic post-surgical pain.

Ware won't say what sort of pain his study will look at for fear of being inundated with calls from sufferers of the chosen malady. While analgesics, physiotherapy, group therapy and the relaxation techniques used in the centre help some, much of the pain caused by damage to nerve roots eludes the standard medical responses. "There's a huge unmet clinical need [for better pain management]," says Ware.

AIDS patients have long known this; an estimated 30% smoke marijuana to assuage the pain, nausea and loss of appetite caused by the disease and AIDS medication. Ware just finished a contract with the Community Research Initiative of Toronto (CRIT), where he helped design the research protocol for a clinical study on the effect of smoking pot on various symptoms of AIDS.

Among his own patients, some are also cannabis users and Ware will note any observations they offer of how the herb helps -- but only if the information is volunteered. Revealing information on illegal drug use, even in a clinical context, requires the patients to sign a consent form in which they acknowledge that if ever the police come questioning the researchers about a particular patient, that patient runs a very small risk of being turned in.

"It's a theoretical risk, but we do it [get signed consent] just in case," says Ware. "It happened in Australia where researchers were looking at LSD and ecstasy."

His own trial will be a small pilot study -- small to ensure that all the bases are covered. There will be questions of licensing the hospital pharmacy, having the police on side, handling the media and finding a government-approved source of low-THC cannabis to act as the placebo. "It will only be by getting the study started that we'll know what to look for in a larger study."

Concerning the potent stuff, the government has already got its supply growing -- 365 metres underground in Flin Flon, Manitoba. The first crop will be ready for harvest by the beginning of 2002 and will allow the government to dispense 100,000 joints of marijuana with a six per cent THC level. Tetrahydrocannabinol is the psychoactive and best-known cannabinoid, but Ware points out that there are at least 60 others, and though the pharmaceutical companies are busy teasing out just which cannabinoid is good for what, the character of each is not well understood.

What the industry will not do is study smoked cannabis, making the work done in universities and community research initiatives doubly important, in Ware's estimation, "since we have to consider the plant's efficacy and safety."

It's work Ware is anxious to get on with and he takes heart in the fact that soon the government is going to have a harvest of cannabis it will have to distribute to approved users and researchers. He wants to understand, for instance, just what it is in the actual smoke or all that's associated with taking a deep puff and holding it that seems to ease so many symptoms. "It's not clear to me," he says, "that the cannabis reduces pain. It may be that it improves the quality of life by reducing depression or insomnia, for instance, which in turn makes the patient less vulnerable to pain."

It's fitting that McGill is supporting the demystification via science of this misunderstood agent. The University has a long history of research into pain and once the study is up and going it won't be the first time that marijuana has been prescribed by McGill physicians. More than 100 years ago, Sir William Osler prescribed the herb to relieve migraine headaches; prescribing cannabis at the time was commonplace.

Ware isn't sure why cannabis, both as medicine and as a source of fibre used to make cloth and rope, fell out of favour in the 20th century after thousands of years of "occupying an enormous place in human history." The word canvas, for instance, reminds Ware of its origins in the plant name, as does Hampstead, England, where hemp, a species of cannabis grown for fibre, was cultivated. Some suggest that the industries producing the new synthetic fibres, such as nylon and polyester, and who synthesized painkillers played a role in first discrediting then demonizing the ancient herb.

But Ware is optimistic that with the public's interest in plant-source medicine and the pressure on governments to study and regulate herbal medicines, there will be an opening in medical science. "To me, the cannabis study represents a kind of template with which to cross from a plant-based medicine to a clinical trial, to see if the two can intersect. I'd like to look at other herbal medicines, to check for their potency and safety," he says, naming the popular echinacea, St. John's Wort and evening primrose.

"Cannabis today is where alcohol was in the 1920s and morphine was in the '40s and '50s. There's the attitude that 'we can't touch this, it's too dangerous.' But all the fears about morphine weren't realized."