SCIENTISTS COPY POT TO COMBAT DEPRESSION

Scientists have created new compounds that act like cannabis on the brain
to reduce anxiety and depression -- but without the hunger or the high.

By prolonging the punch of the cannabis-like chemicals that the brain makes
naturally, researchers from the United States and Italy have shown in rat
experiments that they can copy certain benefits of the common street drug
with far fewer side effects.

If the new compounds pass in clinical testing, these synthetic cannabinoid
cousins could herald a new generation of antidepressants, offering the calm
of marijuana without the munchies.

But such man-made versions are unlikely to supplant the desire of many ill
people for old-fashioned marijuana. The drug's many touted medical uses are
not simply related to mood. Some people praise marijuana as a pain reliever
and others, those with cancer and AIDS in particular, rely on it to boost
meagre appetites.

While researchers in this study did find that their synthetic compounds had
a modest impact on pain, they were primarily interested in the effects on mood.

Daniele Piomelli, a pharmacology professor at the University of California
at Irvine, explained that he and his colleagues tested two compounds that
appear to work similarly to THC, tetrahydrocannabinol, marijuana's main
active ingredient, but far more gently.

"THC reduces anxiety by binding directly to receptors in the brain and
resulting in its familiar high sensation. The reaction is too strong,
creating marijuana's side effects," said Dr. Piomelli, a senior author of
the report, which is to be published in the January issue of the journal
Nature Medicine.

In the past decade, researchers have realized that THC is pleasurable in
part because it mimics a natural neurotransmitter in the brain called
anandamide, from the Sanskrit word for "bliss." This family of brain
chemicals appears to be involved in mood, pain and a range of physiological
functions.

Both THC and anandamide, for example, bind to the same brain receptors.

Just as researchers of the 1960s and 70s discovered the brain's opiate
receptors and endorphins while studying the effects of morphine, so too is
marijuana research opening new chapters in neurobiology.

Several scientists and drug companies, for example, have been trying to
develop drugs to exploit and enhance anandamide. Last year, Dr. Piomelli's
group published a report that they had discovered a brain substance related
to anandamide that may help to combat obesity.

In this study, Dr. Piomelli's team, which included scientists from
universities in Parma, Naples, and Rome, created two compounds to block the
brain enzyme that breaks down anandamides.

By preventing the breakdown, the researchers report that they were able to
keep higher, natural levels of these neurotransmitters in the brain, which
appeared to reduce signs of anxiety and the infamous high in studies with rats.

Rats given the drugs, for example, squeaked less when isolated and
increased their exploration of otherwise intimidating wide-open mazes.
Meanwhile, the rodents showed no drop in body temperature, or increase in
appetite or lethargy -- all hallmark symptoms of a cannabis high.

The compounds, dubbed URB532 and URB597, appear to work like Prozac, the
well-known antidepressant that also raises the brain's natural levels of
serotonin by blocking it from being recycled.

Still, Dr. Piomelli acknowledged, the new drugs are early in development.
"While the study's results are promising, the road from laboratory to
discovery to available medication is years long, often winding, and
definitely expensive," he said.