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UK: A marijuana breakthrough?

David Kohn

The Scotsman

Friday 05 Nov 2004

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A DECADE ago, when Daniele Piomelli went to scientific conferences, he was
often the only researcher studying cannabinoids, the class of chemicals
that give marijuana users a high. His work often drew sniggers and jokes;
but not any more. At the recent annual Society for Neuroscience conference
in San Diego last week, scientists delivered almost 200 papers on the subject.

Why all the attention? Many scientists believe marijuana-like drugs might
be able to treat a wide range of diseases, far beyond the nausea and
chronic pain typically treated with medical marijuana.

Researchers presented tantalising evidence that cannabinoid drugs can help
treat amyotrophic lateral sclerosis - known as ALS or Lou Gehrig's disease
- Parkinson's disease and obesity. Other researchers are studying whether
the compounds can help victims of stroke and multiple sclerosis.

Although the chemicals work on the same area of the nervous system, the new
drugs are much more refined and targeted than marijuana, with few of its
side effects.

"Cannabinoids have a lot of pharmaceutical potential," says Piomelli, a
neuroscientist at the University of California. "A lot of people are very
excited."

Although the US government opposes the use of medical marijuana, it
generally doesn't restrict cannabinoid research, most of which doesn't
involve the cannabis plant itself. Scientists who use Marinol, a legal but
tightly regulated marijuana-like drug, do need government permission.

Because the cannabinoid system wasn't discovered until the late 1980s -
decades after serotonin, dopamine and other neurotransmitters - researchers
still know relatively little about how it works.

Like all neurotransmitter networks, the cannabinoid system consists of a
series of chemical pathways through the brain and nervous system. Marijuana
produces its effects by activating this pathway, primarily through the
effects of tetrahydrocannabinol (THC), the drug's active ingredient.

Over the past decade, researchers have been following these abundant trails
to determine their real purpose. "You don't have them there to get stoned.
So there must be internal reasons," says Andrea Giuffrida, a neuroscientist
at the University of Texas.

Researchers have learned that endogenous cannabinoids - internal brain
chemicals that activate the system - play a role in tissue protection,
immunity and inflammation, among other functions. The cannabinoid system
also appears to exert wide influence, modulating the release of dopamine,
serotonin and other neurotransmitters.

Giuffrida and others believe cannabinoids can treat degenerative disorders
such as Parkinson's disease and ALS. At the conference, Giuffrida announced
that a cannabinoid drug wards off Parkinson's-like effects in mice. The
disorder destroys neurons in a key part of the brain, causing patients to
lose control over movement.

Giuffrida injected mice with a chemical called MPTP, which mimics
Parkinsons damage. When some of the animals subsequently received a drug
that affects cannabinoid receptors, their nerve cells suffered far less
damage than did the cells of the other mice. This was the first
demonstration that a cannabinoid drug can have this effect.

While he is not sure how the anti-cannabinoid compound works, Giuffrida
suspects it protects neurons by reducing inflammation, a key component in
Parkinson's. Cannabinoids might also slow down ALS, which destroys neurons
that control muscles until victims become paralysed, unable to breathe on
their own.

Neuroscientist Mary Abood first became interested in cannabinoids after
hearing about ALS patients who got some relief from smoking marijuana.

In her study, mice with a variant of ALS were given a combination of THC
and cannabidiol, another compound found in marijuana.

Both substances are cannabinoid agonists, chemicals that activate the
cannabinoid system.

Abood measured the course of the ailment by testing how long the mice could
stand on a slowly rotating rod.

The treatment delayed disease progression by more than seven days and
extended survival by six days. In human terms, this would amount to about
three years. That's a significant improvement over the only existing ALS
drug, riluzole, which extends life by two months.

Also at the conference, researchers at the Institute of Neurology in London
announced results that corroborated her findings. Cannabinoids have also
helped some human ALS patients in one small trial and Abood is trying to
get funding for a larger one.

If cannabinoids can shield human neurons from harm, researchers say, they
might prove useful against other neurological diseases, including mental
illness. Scientists are also looking at whether cannabinoids can help treat
multiple sclerosis, epilepsy and Huntington's disease, while Giuffrida is
beginning a study of their effect on schizophrenia.

Advocates of medical marijuana have long argued the drug can be useful for
treating conditions such as chronic pain, nausea and glaucoma.

Some researchers, however, believe there are better, more precise ways to
stimulate the cannabinoid system. They believe marijuana has too many
negatives to be a truly effective drug, with side effects that include
memory problems, decreased immunity and possible addiction.

Marijuana has another drawback. From a scientific standpoint, Giuffrida
says, it's "a very dirty drug". It contains more than 300 compounds, 60 of
which affect the cannabinoid system, which makes it difficult for
researchers to accurately pinpoint marijuana's effects.

 

 

 

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