 | UK med-mj research: New Scientist Magazine: Cannabis: Prescribing The Miracle Weed |
 Issue 2485, 05 February 2005, page 38.
By Clare Wilson
The drug can be a lifeline, and a fortunate few may soon get it on prescription. But why has it taken so long?
I have had patients commit suicide because they said life had no meaning
for them any more," says William Notcutt, an anaesthetist at James Paget
Hospital in Great Yarmouth, Norfolk, on England's east coast. Notcutt
specialises in treating patients in severe long-term pain. The causes are
varied, ranging from spinal injuries to multiple sclerosis, but most of the
patients have one thing in common: existing medicines don't help them.
"It's not just the pain, it's also what it does to your life," Notcutt
says. "You've lost your job, you have financial problems, your spouse is
fed up. I hear these heart-rending stories of people whose lives are crap."
If there is one thing more frustrating for a doctor than being unable to
deal with a patient's problem, perhaps it is knowing that there is a drug
that could help - but they are not allowed to prescribe it. For Notcutt
that drug is cannabis. Many patients with difficult-to-treat conditions use
cannabis to relieve their symptoms, but in most parts of the world that
makes them criminals. Otherwise law-abiding citizens dislike having to get
their treatments from drug dealers. And the quality of the medication they
get that way is variable to say the least.
But in the next few weeks Canadian regulators will decide whether to
approve an under-the-tongue cannabis spray called Sativex for multiple
sclerosis (MS) patients. As the world's first prescription pharmaceutical
made from marijuana, it would at last allow patients to get their therapy
in a safe and consistent formulation. The product could become available in
the UK in a year or so, and its British manufacturer, GW Pharmaceuticals,
is expected to file for approval soon in Australia and New Zealand.
Sativex will not bring any miracle cures, and in countries like the US
where official hostility to marijuana is ingrained, patients may have a
longer wait for its benefits. All the same, the availability of a cannabis
preparation as a prescription medicine will mark a milestone in a
decades-long battle by doctors and patients for public acceptance of
medical cannabis use.
Marijuana use has a long history. For thousands of years, people have been
harvesting the seeds for food and oil, and making rope from the fibres.
The plant is used in traditional medicine all over the world to relieve
pain and muscle spasms, to prevent seizures and to aid sleep. It may also
alleviate nausea - though it can sometimes trigger nausea in new users -
and it can boost appetite.
But the drug is best known for its effects on the mind: it is an intoxicant
that makes people feel happy and relaxed, and over the past century its
recreational use has become increasingly popular in the west. Cannabis is
not very addictive and its harmful effects are mainly on the lungs, from
smoking. In some users it can trigger delusions and hallucinations, and
there is debate about whether it can cause longer-term psychiatric problems
in a small minority. In the early 20th century, most western governments
responded to what they saw as the growing menace of marijuana by outlawing it.
As for medicinal use, cannabis came to be seen as an obsolete herbal remedy
with unpredictable potency. It disappeared from the US Pharmacopeia and
National Formulary in 1941, and the British National Formulary in 1971.
Until the late 1980s, when Notcutt began investigating the medicinal use of
cannabis, research on the drug was focused mainly on establishing its
dangers to people who used it recreationally, or its effects on animals.
Notcutt's interest grew out of his wish to find something new to deal with
his patients' chronic pain. He found repeated references to the drug in
historical medical texts on pain relief, and a growing body of research on
animals showed that the main active chemical of cannabis,
tetrahydrocannabinol (THC), bound to specific receptors in the brain.
In 1982 a form of synthetic THC had been licensed for relieving nausea
after cancer chemotherapy, so Notcutt's first step was to investigate this
for pain.
He began a small trial in his worst-affected patients, mostly people with
spinal injuries. Some of them said THC helped; some of them said it made
them feel dreadful. Others said it wasn't as good as the "real stuff". Thus
Notcutt was introduced to the underground world of medical marijuana use.
Even in sleepy Norfolk he found a small subculture of people who were
getting what they viewed as an essential medicine from their local drug
dealers.
Notcutt began seeing growing number of MS patients, who said cannabis
relieved their pain and muscle "spasticity" - spasms and stiffness - and
helped them sleep. The next step, Notcutt says, was to find a better way to
give the patients what they wanted. In the early 1990s he and his team
began exploring how they might carry out a clinical trial of cannabis.
They immediately ran into difficulties, because of the drug's illegal
status and the resulting haphazard supply chain. "Are you going to use any
old thing that comes off the Felixstowe docks?" he asks. "What's the
quality, how do you standardise it?" They also failed to come up with a
safe and effective way to administer the drug. Taken orally, marijuana's
potency varies markedly and it doesn't become effective for at least an hour.
Smoke it, and you inhale a bunch of cancer-causing chemicals just as you do
when smoking tobacco.
In California, Donald Abrams, an HIV specialist at San Francisco General
Hospital, was facing similar problems. He was interested in the possibility
that cannabis could help people with AIDS stave off catastrophic weight
loss. "They'd get loss of appetite and diarrhoea and just sort of waste
away," Abrams says. "It was a terrible way to go." In 1992, synthetic THC
was licensed for combating the nausea that is a symptom of AIDS, but, as
with MS patients, many found marijuana more effective. Like the English
patients, they faced supply problems. After a 70-year-old volunteer helper
at his clinic was arrested for giving patients cannabis-laced brownies,
Abrams decided to carry out a formal trial of marijuana.
If anything, he faced even stiffer opposition than Notcutt. In 1994 the
team asked permission from the US Drug Enforcement Administration to obtain
cannabis from a Dutch firm called Hortapharm but was turned down. They next
approached the National Institute on Drug Abuse (NIDA), the only domestic
body allowed to provide marijuana for research. Again they were rejected,
partly because officials said they feared patients might sell their drugs
on the street, and partly because the institute was more interested in
investigating the harm from recreational cannabis use. A third proposal to
NIDA, in 1996, was also turned down.
By then, official attitudes in the UK were showing signs of becoming more
favourable to medicinal marijuana. Paradoxically, this stemmed partly from
anti-drug sentiment. Increasing numbers of MS patients using marijuana were
ending up in court, and many were given light sentences or effectively let
off. Concerned that this was bringing drug laws into disrepute, the
government started to make positive if cautious noises about legalising
medicinal cannabis if a pharmaceutical form of it could be developed.
At the same time, medical research into cannabis was gaining respectability
globally as details began to emerge about the cannabinoids our own bodies
produce (see "Natural high"). But such research was almost entirely carried
out by academics. What pharmaceutical firm would want to risk investing in
such a politically controversial and financially uncertain field?
Enter Geoffrey Guy, a businessman with a background in pharmaceuticals who
was looking for his next venture. Cannabis's long history ruled out the
normal route for making money from a drug: by patenting it as a therapy.
But Guy realised he could gain market exclusivity by developing a drug from
cloned cannabis subspecies to which he owned the plant-breeders rights. Guy
recalls that when he approached government officials for a licence to
research his idea, they needed little convincing. "They were almost
relieved that a company had turned up," he says. "I was pushing on a door
that sprung open."
His new company, GW Pharmaceuticals, bought several strains of cannabis
with consistent high drug yields from Hortapharm and by the late 1990s was
growing and harvesting a crop of 5000 plants. To avoid the variable
absorption of ingested cannabis, the firm decided to produce a spray to be
applied under the tongue, where it would be quickly absorbed into the
bloodstream. And so Sativex was born.
Notcutt agreed to carry out a clinical trial. But despite increasing public
acceptance of the idea of using cannabis medicinally, he found it hard to
get the study approved by his hospital.
It took about a year to get the go-ahead for a small three-month study in
people, some with MS, for whom existing treatments were ineffective against
chronic pain. The results, published last year (Anaesthesia, vol 59, p
440), showed that Sativex provided significant pain relief for 28 of the 34
patients in the study. GW began larger trials on people with MS or chronic
pain, as well as pilot studies in people with cancer.
At this point GW began looking for a pharmaceutical company with the muscle
and money to help market Sativex. Rumours circulating at the end of 2002
suggested that Guy was in talks with a major-league company, perhaps
GlaxoSmithKline or AstraZeneca. Guy won't say, because before the deal was
done, the firm got cold feet. They were spooked by the "c-word", Guy says.
Cannabis was too controversial for the American board members. GW had to
find another partner, and in May 2004 it finally struck a deal with the
German-based multinational Bayer.
In the meantime, the larger clinical trials were starting to yield positive
results. GW has applied for a licence from the Medicines and Healthcare
Products Regulatory Agency (MHRA) to sell the drug in the UK. The MHRA has
asked for a "confirmatory study", to prove that the reduction in muscle
spasticity seen with Sativex brings meaningful benefits to patients. GW
says this will take several months.
But it is in Canada, where patients can legally use cannabis for medicinal
purposes, that Sativex is closest to being licensed. The preparation was
given preliminary approval in December, and GW and the Canadian regulatory
agency are now thrashing out exact terms for a licence to allow Sativex to
be sold as a prescription drug. Assuming they reach agreement, Sativex
could reach pharmacies within a couple of months. GW says it will be
applying for licences in "other Commonwealth countries", probably Australia
and New Zealand.
It may not be long before Sativex is joined by other cannabis preparations.
A non-profit group, the Institute for Clinical Research in Berlin, Germany,
is developing oral cannabis capsules, called Cannador. In November 2003 a
study in 630 MS patients produced equivocal results (The Lancet, vol 362, p
1517). While the formal scoring system for measuring muscle spasticity
indicated that Cannador performed no better than a placebo, the patients
themselves felt it helped. Martin Schnelle, who conducted the trial, says
that there are widely acknowledged problems with the formal scoring system
used. "There are medicines that are already licensed for treating
spasticity that have failed on this scale," he says. The group is planning
a further study this year in which the patients' reports will be the main
measure by which the drug's effectiveness is judged.
In the US, the NIDA has become more open to research on the benefits of
cannabis, and Abrams is studying its ability to ease pain due to nerve
damage in HIV, and nausea and vomiting after cancer chemotherapy. He is
investigating a device called the Volcano, which heats cannabis to the
point of vaporisation without burning it, which he says is less harmful
than smoking it in a joint because it releases fewer carcinogens. While
Abrams welcomes products like Sativex, he suggests that some people will
always prefer marijuana to a commercial preparation - not least because
they can grow it themselves.
But however cultural attitudes to street or home-grown cannabis change, its
availability in standardised, licensed preparations such as Sativex and
perhaps Cannador will be the key to its wider medical use. GW is planning
studies of its possible benefits for people with a range of conditions from
Crohn's disease to rheumatoid arthritis and heroin addiction. If positive,
Canada's decision will signal a big change in the status of cannabis, says
Philip Robson, the firm's medical director. "It's the dawning of a new
clinical research era."
(c) Copyright New Scientist magazine
www.newscientist.com
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