CANNABIS: AN EVIL WEED OR A POT OF GOLD?

PHARMACEUTICALS: The claimed medical benefits of the controversial drug are
being subjected to rigorous scientific testing.

Queen Victoria took it for period pains. The Chinese mixed it with wine to
make a powerful analgesic, while throughout medieval Europe it was taken to
control epilepsy.

Cannabis has been used by doctors for thousands of years. Until the
emergence of the modern pharmaceuticals industry at the end of the 19th
century, which shifted drug development from plants to synthetic chemicals,
cannabis was a staple of the medicine chest.

With little concrete research into cannabis, a polarised debate has rumbled
on about the plant for years. Supporters have claimed it to be a medical
goldmine neglected because of political pressure, particularly since its
use was outlawed in the UK in 1971. Meanwhile, sceptics have suggested that
medicine has ignored cannabis because much better drugs are already available.

Now some of these questions are about to be answered. After centuries of
experimentation, medicines made from cannabis plants are being subjected
for the first time to the rigorous procedures of modern science -
large-scale clinical trials using hundreds of patients. And the results
will shortly be known.

"It is rare that you find so much research about a potential medicine,
without any products to support it," says Geoffrey Guy, chief executive of
GW Pharmaceuticals, a UK biotechnology company which has pioneered some of
the trials. "We have not been able to explain cannabis therapeutically
because of its illegal status."

The Medical Research Council has sponsored two large sets of clinical
trials to study the effectiveness of cannabis in treating multiple
sclerosis and post-operative pain. John Zajicek, consultant neurologist at
Derriford Hospital in the UK who is leading the MS research, is due to
report the results of the three-year trial before the end of the year.

Meanwhile, GW Pharmaceuticals has already conducted clinical trials into
use of a cannabis-based product developed for MS and neuropathic pain. The
full results are expected to be published shortly; in September the company
said that in a trial of 66 MS patients, pain and sleep disturbance had been
reduced.

Based on these studies, GW has also applied to the UK medicines regulator
for approval to market a cannabis-based product, Sativex, and hopes to
receive a response by the end of the year.

All this activity has run in parallel to the separate discussion about
legalising recreational use of cannabis. However, it is part of a broader
international movement pushing for the medical use of cannabis, spearheaded
by many patients who use the drug and claim it helps. Last month, the
Netherlands permitted doctors to prescribe cannabis to patients with
terminal cancer, Aids, HIV, MS or Tourette's Syndrome. The move followed a
similar decision by Canada earlier in the year.

In the US, there has been a long-standing campaign to allow patients to
smoke cannabis, which gained momentum when a California referendum in 1996
voted to allow seriously ill patients to grow or possess cannabis.

These campaigns have been propelled by recent advances in the understanding
of cannabis. In the early 1990s, scientists discovered that human brains
have receptors - proteins in the membrane of cells - that can be activated
by cannabinoids, the molecules that are found only in the cannabis plant.
There are an estimated 60 different cannabinoids in cannabis, the main one
being THC.

Shortly afterwards, scientists also discovered that the brain naturally
contains a type of cannabis-like molecule, "endocannabinoids", that can
activate those receptors.

While the potential impact on the central nervous system had long been
claimed by some researchers, these developments gave an in-sight into the
actual mechanism of action of cannabis and provided more clues to how
cannabis-based treatments might be designed.

GW says progress has been made on other fronts. It has built a
computer-controlled glasshouse that can provide plant extracts with
consistent levels of purity and it has also developed different delivery
mechanisms, including the oral spray that is used in Sativex. Previous
attempts at developing drugs from synthetic THC were not commercially
successful, partly because the capsules were absorbed slowly by the body.

Despite the vast library of new research, there is still a considerable
amount of scepticism about cannabis among some medical researchers. The
British Medical Journal published a withering rebuke of the use of cannabis
in pain relief in 2001 based on an examination of nine published studies,
and suggested that the potential depressive effects could limit its
attractiveness.

"Cannabis is clearly un-likely to usurp existing effective treatments for
post-operative pain," says Fiona Campbell at the Pain Management Centre in
Nottingham.

The BMJ received a volley of letters the following week complaining that
cannabis should not be ruled out on the basis of very limited amounts of
research and pointing out that it was being considered for highly specific
medical needs, such as MS and neuropathic pain, which are poorly treated at
the moment.

There has also been spill-over from the debate about recreational use of
cannabis. Just as work on cannabis's potential medical benefits has
mushroomed, so has research into potential links with mental illness.

Among a series of alarming reports, one study conducted in Dunedin in New
Zealand and published last November examined a group of 1,000 people born
in the early 1970s and followed them through to the age of 26. It concluded
that those who used cannabis before the age of 15 were four times more
likely to be diagnosed as schizophrenic than those who did not.

The researchers stressed the results did not show whether cannabis-use
caused mental illness. But Robin Murray, a psychiatry professor at Kings
College, argues: "Using cannabis in adolescence increases the likelihood of
experiencing symptoms of schizophrenia in adulthood."

Dr Guy refuses to be drawn on the issue of recreational use, but adds that
this research is not relevant to the case for medicinal cannabis. The
patients involved in these studies have usually taken considerable
quantities of cannabis from an early age, he says, whereas the patients in
the company's clinical trials use only low doses that do not give them a
"high". He also believes that the mix of cannabinoids used in Sativex -
notably THC and another called CBD - produces fewer side-effects than THC
alone. "If there is a causal link between psychosis and cannabis, it is
still not a matter of concern for patients taking it as a (prescription)
medicine," says Dr Guy.

If strong medical benefits for cannabis are demonstrated, these arguments
will likely carry the day.

But given the concern about potential side-effects, there are likely to be
strict controls on medical cannabis, similar to those used for morphine,
codeine and other opiates - drugs derived from the opium poppy that also is
the source of heroin.

Indeed the two might come as a package. Some researchers believe it might
be most effective in pain relief when used in combination with codeine -
creating a double dose of cannabis and opium.