Pubdate: Mon, 02 Dec 2002
Source: Globe and Mail (Canada)
Copyright: 2002, The Globe and Mail Company
Author: Carolyn Abraham


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 

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.
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MAP posted-by: Larry Stevens