HTTP/1.0 200 OK Content-Type: text/html Prescribing The Miracle Weed
Pubdate: Sat, 05 Feb 2005
Source: New Scientist (UK)
Page: 38
Copyright: New Scientist, RBI Limited 2005
Author: Clare Wilson
Cited: GW Pharmaceuticals
Cited: Institute for Clinical Research
Bookmark: (Cannabis - Medicinal)
Bookmark: (GW Pharmaceuticals)


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 

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." 
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