MARIJUANA-LIKE DRUGS COULD FIGHT DISEASES

Refined Chemicals Show Promise in the Treatment of Obesity, Als And
Parkinson's

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 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 here presented tantalizing 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," said Piomelli,
a neuroscientist at the University of California, Irvine.

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.

Researchers have learned that endogenous cannabinoids - internal brain
chemicals that activate the system - play a role in tissue protection,
immunity and inflammation. 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 said 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 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 paralyzed, unable to breathe on
their own.

In a study by neuroscientist Mary Abood , 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 more than seven days and
extended survival six days. In human terms, this would amount to about
three years. That's improvement over the only ALS drug, riluzole,
which extends life two months.

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.

If cannabinoids can shield human neurons from harm, researchers say,
they might prove useful against other neurological diseases, including
mental illness.