DEBATE RAGES ON DRUG'S BENEFITS

There's A Surge in Interest on Marijuana Research With Evidence
Emerging of Its Ability to Relieve Pain and Its Apparent Safety

After all the usual and proper medical approaches did nothing for her
pain, Cheryl Campbell, a nurse and mother, says she finally built up
the courage to ask her doctor: "How do you feel about prescribing me
marijuana?"

The 30-year-old Ottawa woman suffers from fibromyalgia and chronic
fatigue syndrome. Her pain is bodywide: a constant, sometimes stabbing
ache in her back, hips, knees, shoulders and virtually every joint.
Doctors once put her on morphine. It cut the pain, but she couldn't
function. She says her mind felt so heavy with fog she couldn't carry
on a conversation.

She's been using marijuana for pain for two years; she has a federal
licence to possess it. She says it helps her sleep at night. In the
morning, it helps ease the stiffness in her hips and back enough that
she can make it into the shower.

Campbell says she owes her ability to get through each day to a drug
that critics condemn, especially when it's smoked, which is how most
of the thousands of Canadians who self-medicate with pot prefer to
take it. The U.S. Drug Enforcement Administration was unequivocal
earlier this year: Smoked marijuana is not medicine, and it's not safe.

"No matter what medical condition has been studied," the agency ruled,
"other drugs already approved by the (U.S. Food and Drug
Administration) have been proven to be safer than smoked marijuana."

But research into medicinal marijuana is undergoing a surge of
interest, with more evidence emerging not only of its ability to ease
human suffering, but also of its apparent safety.

Some say cannabis may be less toxic to humans than over-the-counter
pain relievers. Four small but scientifically controlled experiments
in recent years have concluded that smoked cannabis can provide
moderate relief from chronic, severe non-cancer pain, including
HIV-related nerve pain, and post-traumatic neuropathy, a dreaded
condition that can follow an injury or medical procedure. Both are
notoriously resistant to conventional treatments.

Scientists are only beginning to tease out the possible anti-cancer
properties of pot. Early experiments in animals suggest that purified
forms of THC and cannabidiol - two major constituents of marijuana -
can induce certain cancer cells, including breast cancer cells, to
essentially kill themselves off, a process known as apoptosis. The
cells self-destruct; they stop dividing and spreading. Cannabinoids
also seem to shut down a tumour's lifegiving blood supply.

Meanwhile, researchers across Canada are testing cannabinoids against
arthritis, glaucoma and gastrointestinal inflammatory diseases, such
as Crohn's.

"Science is just scratching the surface," says Dr. Mark Ware, head of
the Canadian Consortium for the Investigation of Cannabinoids and
director of clinical research at the Alan Edwards Pain Management Unit
at the Mc-Gill University Health Centre.

In Canada, synthetic versions of THC and other pure cannabinoids are
already available by prescription - pills and sprays approved for
cancer pain, for nausea associated with chemotherapy, to stimulate
appetite and for the relief of the pain and spasticity of multiple
sclerosis.

Medical marijuana, Ware argues, is essentially just a different
delivery system for cannabinoids. It's crude, he acknowledges. It's
also associated with potential harms through the sheer act of burning
the plant and smoking it. But even then, he says the evidence is
uncertain. "It's not a done deal that smoking cannabis alone is as
potent a cancer-causing agent as tobacco," Ware says.

According to U.S. drug enforcement officials, while smoked marijuana
can cause changes in lung tissue that may very well unleash cancer,
"it's not possible to directly link pot use to lung cancer based on
existing evidence."

But does it have any legitimate role in medicine?

Modern interest in cannabis exploded in the 1980s when researchers
discovered all mammals, notably humans, have an endogenous, or
built-in, cannabinoid system. Essentially, we make our own marijuana.

Two types of receptors for cannabinoids - CB1 and CB2 - are found in
the brain and spinal cord, nerve cells and immune tissues. The body
produces a natural, THC-like chemical called anandamide, the so-called
"bliss chemical," that binds to these receptors. Anandamide has been
found to play a part in pain, anxiety and depression.

The reason we don't walk around high all the time is that anandamide
is released only in response to some kind of noxious or painful
stimuli, such as an injury or inflammation.

The neurotransmitter latches onto the receptors and, in the case of
pain, helps settle down the firing of nerves in the pain pathway. But
it's broken down quickly, chewed up by enzymes so rapidly that it
never reaches a level sufficient enough to cause a high.

When someone smokes marijuana, those exogenous cannabinoids "are
obviously going to hit all the cannabinoid receptors in the body,"
explains Dr. Jason McDougall, associate professor in the departments
of pharmacology and anesthesia at Dalhousie University in Halifax.

And since one of those receptors, CB1, is most prominent in the brain,
"that's why we get a lot of those psychoactive effects of the drug."

But the cannabinoids in pot also occupy receptors in the peripheral
nerves involved in the body's pain system, as well as nerves
controlling movement and other functions.

Studies of patients with MS have found that cannabis can help with
muscle pain, tremors and depression; patients have reported feeling
better able to move.

Laboratories around the world are examining ways to harness this
potential in a way that minimizes psychotropic side effects. Some are
trying to develop a drug that acts peripherally; others are looking
for drugs that block the rapid breakdown of our own endogenous
cannabinoids - "the same way we treat depression by giving
antidepressants that can inhibit or interfere with the breakdown of
certain chemicals in our brain like serotonin," says Dr. Mary Lynch,
director of the pain management unit at Queen Elizabeth II Health
Sciences Centre in Halifax and past president of the Canadian Pain
Society.

Despite its widespread illegal use, there are few, "if any," reports
of fatal overdoses from cannabis, said Oxford University professor Les
Iversen, now chairperson of the U.K. government's Advisory Council on
the Misuse of Drugs. By contrast, thousands die each year from
"catastrophic" bleeding in the gut caused by nonsteroidal
anti-inflammatory drugs, or NSAIDS, he said.

Doctors say that what makes cannabinoids safer than opioid pain
medications is that cannabinoid receptors, unlike receptors for
opioids, aren't present in high numbers in the brain stem regions that
control breathing and heart rate. "This is one of the reasons
cannabinoids are generally safer than many of the other drugs used to
treat human disease and pain," says Lynch.

The most common side effects are sedation and foggy thinking. "You can
also get high," Lynch says. "But many of our patients adjust the dose
so they can avoid the side effects and aim for the therapeutic
effects, similar to the way we use any drug."

Ware of McGill said that for cases of severe intractable pain, the
prescription oral cannabinoids often don't work. Some patients prefer
the inhaled mode because it's the fastest way of experiencing its effects.

McDougall of Dalhousie has found that when synthetic cannabinoids are
injected into the joints of arthritic rats, "we can control the pain
in the joint itself" while avoiding the psychoactive effects of the
compounds.

"We don't have great agents now," he says. Many drugs used for
arthritis have "multiple negative side effects," he says, including a
potential increased risk for cardiovascular disease, kidney disease
and gastro-intestinal bleeding associated with long-term use of
NSAIDS. "There are still a lot of arthritis patients out there who are
not getting adequate pain relief for their disease," he said.

Many are turning to pot. "A lot of patients who are on medical
marijuana are taking it to control their arthritic pain," he says.

That makes Dr. Meldon Kahan nervous.

He and others worry that smoked marijuana's promotion among users as a
legitimate medicine, especially for pain, is driving a rise in illicit
use at a time when Canadians are already among the highest per-capita
users of pot in the Western world.

"A lot of people - particularly young people - are harmed by the
notion that cannabis is this harmless herb," says Kahan, a physician
and associate professor in the department of family medicine at the
University of Toronto.

Kahan says cannabis may trigger psychosis in people with a genetic
vulnerability. He says more users - young and old - are becoming
addicted. "It's harming their social relationships, their work."

For select conditions such as HIV-related neuropathy, cannabis "may
very well have benefit," says Kahan, formerly of the Centre for
Addiction and Mental Health in Toronto. But others might be confusing
its "very mild" analgesic effects with its moodaltering ones, he said.

"Cannabis, especially daily use, makes people feel relaxed. It reduces
anxiety and stress. People feel mellow and so they may perceive their
pain as being blunted, or milder."

Despite the polarizing nature of pot, "we have to take the middle
ground and say, 'Where are the potential benefits?' " Ware says.

Campbell, a registered practical nurse who can no longer work because
of her pain, says that, if it were not for marijuana, "I don't know if
I'd ever get out of bed and get moving."

After 10 years of pain, "it's the only thing that helps."

[sidebar]

TO SMOKE OR NOT TO SMOKE?

PROS:

May offer pain relief to people suffering from chronic neuropathic
pain - pain caused by accidental or surgical injury to nerves

Effective for HIV-related pain and an appetite stimulant for people
living with AIDS

May provide relief for painful muscle spasms due to multiple
sclerosis

May reduce opioid dose in treatment of chronic, noncancer
pain

Cannabis smoking by itself does not appear to be major risk factor for
head, neck or lung cancer

Can improve mood and sleep in patients with chronic
pain

CONS:

Can cause drowsiness, dry mouth, headache; can impair psychomotor
skills

Increased risk of heart attack within one hour of use

May trigger psychosis in those who are vulnerable due to personal or
family history

May cause changes in lung tissue with long-term use that may lead to
cancer

Possible increased risk of cardiovascular disease

Little known about longterm effects