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Canada: Scientists copy pot to combat blues

Carolyn Abraham

Globe and Mail, Canada

Monday 02 Dec 2002

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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.


 

 

 

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