Pubdate: Mon, 01 Nov 2004
Source: Baltimore Sun (MD)
Copyright: 2004 The Baltimore Sun, a Times Mirror Newspaper.
Contact:  http://www.baltimoresun.com/
Details: http://www.mapinc.org/media/37
Author: David Kohn, Sun Staff
Bookmark: http://www.mapinc.org/mmj.htm (Cannabis - Medicinal)
Bookmark: http://www.mapinc.org/find?232 (Chronic Pain)

RESEARCHERS FIND DRUG HIGH A POTENT FIELD OF INQUIRY

SAN DIEGO - 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 snickers and jokes - but no more. At the annual Society 
for Neuroscience conference last week, scientists here delivered almost 200 
papers on the subject.

Why the attention? Many scientists think 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 here presented tantalizing evidence that cannabinoid drugs can 
help treat amyotrophic lateral sclerosis (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," said Piomelli, a 
neuroscientist at the University of California, Irvine. "A lot of people 
are very excited."

Although the federal 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, or THC, the drug's main 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," said Andrea Giuffrida, a neuroscientist 
at the University of Texas Health Sciences Center in San Antonio.

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 think cannabinoids can treat degenerative disorders 
like Parkinson's disease and ALS.

At the conference, Giuffrida announced that a cannabinoid drug wards off 
Parkinson's-like effects in mice.

The disorder, which afflicts more than 1 million Americans, destroys 
neurons in a key part of the brain, causing patients to lose control over 
movement.

Giuffrida, with colleagues David Price and James Roberts, injected mice 
with a chemical called MPTP, which mimics Parkinson's damage. When some of 
the animals subsequently received a drug that blocks 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 isn't 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 paralyzed, unable to breathe on their own.

ALS Experiments

Neuroscientist Mary Abood first became interested in cannabinoids after 
hearing about ALS patients who got some relief from smoking marijuana. So 
she began animal experiments at the California Pacific Medical Center in 
San Francisco.

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. "I was very excited when 
I got my initial results," Abood said.

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 looking at whether cannabinoids can treat multiple 
sclerosis, epilepsy and Huntington's disease, while Giuffrida is beginning 
a study of their effect on schizophrenia.

Some schizophrenics say marijuana lessens their psychotic symptoms, and 
studies have shown that schizophrenic patients have abnormal brain levels 
of cannabinoids.

Marijuana-like drugs might also help treat stroke. Soon after a stroke, the 
injured brain region is flooded with a neurotransmitter called glutamate, 
which at high levels is lethal to neurons.

Cannabinoids seem to protect against this destruction, and Israeli 
scientists are studying whether increasing cannabinoid levels soon after 
stroke can minimize harm.

Advocates of medical marijuana have long argued that the drug can be useful 
for treating many conditions, particularly chronic pain, nausea and 
glaucoma (in the latter, marijuana works by temporarily decreasing pressure 
around the eye).

Although they don't dispute this view, most researchers think 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 possibly 
addiction. (Some researchers dispute this.)

'A Very Dirty Drug'

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. Scientists don't understand what most of these substances do or how 
they work together. This complexity makes it hard for researchers to 
pinpoint marijuana's effects.

One cannabinoid, Marinol, is available legally. The compound, which 
contains THC in a pill form, is usually prescribed for nausea and for 
appetite loss among AIDS patients.

But Marinol has the same psychoactive effects as marijuana. So the key, 
Piomelli says, is "getting the effects without the side effects."

To that end, Piomelli has developed a compound called URB597, which doesn't 
flood the body with cannabinoids, as Marinol and marijuana do. Instead, it 
slows the breakdown of the cannabinoids in the system. He thinks the drug 
may help treat pain, anxiety and even depression without making patients 
stoned and forgetful. He and others are testing it on animals.

Another cannabinoid compound, Rimonabant, will likely be available much 
sooner, as a diet drug. It lowers cannabinoid levels and seems to reduce 
appetite - the opposite effect of the intense "munchies" that marijuana 
users experience.

Early results from human clinical trials indicate that it helps patients 
lose weight, although some subjects report side effects that include 
diarrhea and depression. The drug might also be able to reduce cravings for 
alcohol and nicotine, researchers say.

For Piomelli, this explosion of research has an added bonus. A few years 
ago, when he told people what he did for a living, they'd often giggle and 
ask him if getting high was part of his job. These days, he doesn't hear as 
many snickers.

"The work is so exciting that it is eliminating the stigma of being 
associated with marijuana," he says. "People realize that it's not just 
'Let's take some marijuana and give it to people.'" 
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MAP posted-by: Richard Lake