ATTACK OF THE MUNCHIES

Feeling ravenous? Even law-abiding citizens fall prey to the cravings
triggered by cannabis

RAIDING the fridge in the middle of the night is an all too common
side-effect of smoking cannabis. But you don't have to smoke dope to
get the munchies. Certain chemicals you're born with can spark off an
attack of hunger as well.

Even the most upright citizens have naturally occurring cannabis-like
molecules circulating in their brains. Now scientists are suggesting
that these molecules trigger intense hunger pangs and may even
contribute to obesity.

Normally, mice that have been starved eat voraciously. But George
Kunos and his colleagues at Virginia Commonwealth University in
Richmond found that the absence of cannabis receptors makes the mice
much less hungry. Genetically modified mice lacking the receptors ate
far less food than usual after being starved for 18 hours, as did
unmodified mice that had been given drugs to block the receptors.

But you can have too much of a good thing. In a finding that could
link cannabinoids to human obesity, Kunos and his team found high
levels of cannabis-like substances in the brains of excessively fat
mice. The mice were born with a genetic defect that prevented them
from making leptin, a hormone that is known to have a key role in
curbing appetite.

It was the discovery of leptin's role that transformed obesity
research in the 1990s. But how the hormone tones down hunger has never
been quite clear. Now Kunos believes naturally occurring cannabinoids
could be a vital piece of the puzzle. In its latest experiments, his
team has found that injecting leptin into rats and mice automatically
led to a sharp drop in cannabinoid levels.

The finding backs up earlier work by Raphael Mechoulam and his
colleagues at the Hebrew University in Israel, who found that
injecting newborn mice with drugs that neutralise the effect of
cannabis dramatically depressed the mice's appetite. The mice stopped
suckling and died.

So could too much natural cannabinoid in the brain make people fat?
"It's reasonable to speculate that it contributes to some forms of
obesity," says Kunos. "But so far we have no direct evidence."

In France, though, scientists are already giving obese people an
experimental drug designed to block cannabinoid receptors. In a trial
lasting 16 weeks, a compound code-named SR141716 was given to the
patients to see if it would help curb their hunger pangs. The full
results won't be revealed until later this year, but Francis Barth of
the Montpellier-based drugs company Sanofi-Synthelabo, which ran the
study, says the patients lost more weight than a control group.