CANNABIS MAY FIGHT ARTHRITIS

BOSTON-- A synthetic compound developed from an ingredient in marijuana
could be useful in treating rheumatoid arthritis without generating the
buzz of marijuana, according to findings presented yesterday by a
University of Massachusetts Medical School professor.

Sumner H. Burstein said his laboratory's studies indicate that the compound
- -- ajulemic acid -- can thwart one of the body's chemicals that contributes
to the destructiveness of rheumatoid arthritis.

In addition, studies in mice show that the compound can protect joints from
damage, and a small study in humans has suggested the drug is safe, Mr.
Burstein said.

"We believe that (the compound) will replace aspirin and similar drugs in
most applications primarily because of a lack of toxic side effect," Mr.
Burstein said.

Mr. Burstein presented his findings yesterday at the American Chemical
Society's annual meeting. His results were reported during a poster
session, in which scientific teams display charts, graphs, photos and
condensed descriptions of their work. Among the authors of Mr. Burstein's
poster was Dr. Robert B. Zurier, a professor of medicine, cell biology and
pathology at UMass who has collaborated with Mr. Burstein on ajulemic acid.

Ajulemic acid is a synthetic compound that Mr. Burstein developed and then
patented in 1992. He named it by putting together the first letters of the
names of his grandchildren: Adam, Julia and Emily.

Atlantic Technology Ventures Inc. of New York licensed the compound, also
known as CT-3, in the mid-1990s. It commissioned animal studies and human
studies that suggested the drug was safe and had no mood- altering effects.

Then last month, Indevus Pharmaceuticals Inc. of Lexington licensed
exclusive worldwide rights to the compound from Atlantic Technology
Ventures. Indevus is backing a study of the compound in 21 chronic pain
patients in Germany.

"The reason our guys liked it so much is it seems to have a lot of activity
without the psychotropic effects you get with other drugs," said William B.
Boni, Indevus vice president of corporate communications.

Those "effects," of course, are the infamous marijuana high. And the fact
that marijuana is illegal has made it one of the most controversial sources
of medical research.

Even as states have passed medical marijuana laws, the U.S. Supreme Court
has affirmed federal law that declares marijuana a substance with no
medical benefits. Some researchers studying marijuana, or cannabis, have
reported difficulty in getting federal grants or purchases of cannabis from
the government for their studies.

Mr. Burstein said that has not been the case with his research, which has
been going on for more than 30 years with government support.

"In the beginning, the thrust was to answer the question, 'Is it harmful?'
" he said. "In the '70s, all the people in the field were working to
resolve those issues ... It's certainly safer than alcohol, nicotine. But
the political issue was not settled at all. It's a very emotional issue."

Another problem is that the one marijuana-derived drug on the market,
Marinol, has been criticized because some patients taking it experience the
mood-altering effects of marijuana.

Ajulemic acid is different, however, because it is a synthetic compound
that Mr. Burstein developed from a metabolite of tetrahydrocannabinol, or
THC, the main ingredient in marijuana that produces a high. Metabolites are
substances that the body produces as it processes a drug.

In the research he reported yesterday, Mr. Burstein said he and his
collaborators started with blood and joint cells from healthy people and
patients with inflammatory arthritis. Rheumatoid arthritis occurs when the
body comes under attack from its own powerful immune system.

The researchers added ajulemic acid to the cell samples, then exposed them
to a toxin that produces inflammation.

The researchers found that ajulemic acid reduced the cells' secretion of
interleukin 1-beta, a substance produced by the body and associated with
joint destruction in rheumatoid arthritis. The compound had no effect on
the cells' production of tumor necrosis factor, another substance produced
by the body and considered a key player in rheumatoid arthritis.

Mr. Burstein said the findings supported earlier studies in rats, which
showed that ajulemic acid protected the animals from joint destruction,
although not from inflammation.

"Almost 80 percent of the animals were spared from bone destruction, even
though there was evidence the joints had become inflamed," he said.

Mr. Burstein said ajulemic acid also appears to inhibit the body's
production of other potentially harmful substances: T cells, which are part
of the immune system, and the COX-2 enzyme, which is the target of the
popular osteoarthritis drug Celebrex.

The way the drug acts remains unknown and is a subject that Mr. Burstein
said he hopes to continue studying. He is seeking additional federal grant
money to support the work.

If it proves safe and effective in humans, researchers could find
additional applications for ajulemic acid. Atlantic Ventures reported
earlier this year that British researchers observed that the drug reduced
spasticity in animals with the symptoms of multiple sclerosis. The findings
are encouraging for researchers who have had to fend off skeptics of
cannabis research for years, Mr. Burstein said.

"It's become a legitimate area of science," Mr. Burstein said. "For years
we were considered outsiders, outside the mainstream of biological science."