FIND MAY YIELD ALTERNATIVE TO MEDICINAL POT

Scientists at the Scripps Research Institute have found a way to duplicate
the medically therapeutic effects of marijuana in mice by blocking an enzyme.

The researchers said their findings could one day result in a chemical
alternative to smoking marijuana -- which is banned under federal law -- as
a way of treating chronic pain and the side effects of cancer and AIDS drugs.

The breakthrough centers on an enzyme that degrades a substance in the
brain that plays a role in pain, appetite and memory.

Benjamin Cravatt, an assistant professor at the Skaggs Institute for
Chemical Biology at Scripps, said the research team was relieved to
discover it could focus on a very simple target.

"My fear (was) that there would be 50 or 60 enzymes that would all
individually be able to degrade this stuff," Cravatt said. "That would be a
nightmare pharmaceutically. This says you only need to worry about one enzyme."

The findings, made with the help of researchers from Virginia Commonwealth
University, were published this month in the journal Proceedings of the
National Academy of Sciences.

The enzyme, called fatty acid amide hydrolase, or FAAH, is responsible for
the breakdown of anandamide, which occurs naturally in the brain.

Inhibiting the enzyme made it difficult for the mice to break down
anandamide, Cravatt said. And that allowed the substance to produce the
same reduced pain sensitivity triggered by THC, the active ingredient in
marijuana.

The work confirms that the enzyme "is a good target to at least
investigate" for treating chronic pain, he said.

The enzyme was blocked by breeding mice without specific genes. Since that
is not feasible in humans, Cravatt said, one of the next major goals is to
try to create a pharmaceutical method to inhibit FAAH, again working with
mice, and see if it has the same therapeutic benefits.

Unlike marijuana -- which can temporarily diminish mobility, memory and the
ability to perform complex tasks -- the genetic technique of blocking the
enzyme didn't appear to produce any harmful side effects in the mice.

As a result, Cravatt speculated that a chemical method to perform the same
function could become preferable to medical marijuana.

Marijuana is thought by some to help relieve pain and nausea, loss of
appetite and the wasting caused by drugs used to treat cancer, AIDS and
other illnesses. But its use is illegal, and the U.S. Supreme Court in May
ruled that California voters in 1996 were not entitled to enact an
exception to the law for "medical necessity."

Under way for more than four years, the research was supported by grants
from the National Institutes of Health, the Baxter Foundation, the Searle
Scholars Program, the National Science Foundation and the Skaggs Institute.