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RAIDING the fridge in the middle of the night is an all too common
side-effect of smoking cannabis. But you don鈥檛 have to smoke dope to get the
munchies. Certain chemicals you鈥檙e 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鈥檚 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鈥檚
appetite. The mice stopped suckling and died.

So could too much natural cannabinoid in the brain make people fat? 鈥淚t鈥檚
reasonable to speculate that it contributes to some forms of obesity,鈥� says
Kunos. 鈥淏ut so far we have no direct evidence.鈥�

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 codenamed SR141716 was given to the patients to see if it would help
curb their hunger pangs. The full results won鈥檛 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.