A dangerous pathway...
By David Concar

Is this yet another moral panic, or is the
discovery that cannabis and heroin have similar
effects on the brain conclusive evidence that smoking
marijuana leads to the hard stuff? TWO studies
claiming that marijuana produces chemical changes in
the brain that could give people a desire for harder
drugs have provoked controversy among
neuropharmacologists.

Until now there has been no firm evidence to support
the idea that marijuana is chemically addictive or that
it makes people more likely to succumb to hard drugs.
But in the latest issue of Science (vol 276, pp 2048
and 2050) two research teams claim that cannabis
pushes the same kinds of chemical buttons in the
brain as heroin.

George Koob and Friedbert Weiss of the Scripps
Research Institute in La Jolla, California, and a team
at the Complutense University in Madrid led by
Fernando Rodríguez de Fonseca studied the effects of
cannabinoids on corticotropin releasing factor (CRF),
a brain hormone that is released during stress and
pain. When rats on heroin are forced to quit, their
CRF levels soar as they go through withdrawal.

The researchers wanted to see if cutting off
cannabinoids causes a similar surge in CRF. Because
cannabinoids linger in the brain for days, the team had
to simulate rapid withdrawal by using a second drug
to block the brain's cannabinoid receptors. When they
did this in rats, the animals' CRF levels jumped
threefold.

In the second study, Gaetano Di Chiara and his
colleagues at the University of Cagliari in Italy
focused on a tiny cluster of cells in the midbrain
called the nucleus accumbens. Addictive drugs all
seem to boost levels of the neurotransmitter dopamine
in this structure. This dopamine surge is thought to
play a vital role in addiction, perhaps by training the
brain to associate a drug with pleasure.

Di Chiara's team had previously discovered that
cocaine, heroin, alcohol and nicotine all trigger the
dopamine surge in rats. The new study adds cannabis
to the list. "We now know that there's a thread linking
all these drugs," says Di Chiara.

But it is the idea that there is a specific link between
marijuana and heroin that makes his new study so
controversial. The Italian researchers found they
could boost dopamine levels by injecting rats with
heroin or tetrahydrocannabinol, the active ingredient
in marijuana. But the dopamine responses to both
drugs could be blocked by giving the animals
compounds that shield receptors in the brain from
heroin. Di Chiara argues that cannabis boosts
dopamine levels by unleashing opioidlike substances
in the brain that pull the same chemical levers as
heroin.

Other neuropharmacologists reject the claim that the
studies support the idea that cannabis use opens the
door to heroin addiction. Roger Pertwee of the
University of Aberdeen points out that the sudden
withdrawal provoked in the CRF study would never
happen normally.

Lester Grinspoon of Harvard University suspects that
the dopamine surge is a general pleasure response,
rather than a specific reaction to an addictive drug. "If
you hit a home run in baseball, the same pathway is
probably activated, but that doesn't mean you're going
to go out and get addicted to drugs," he says.

Tony Dickenson, an expert on opioid pharmacology
at University College London, questions the
significance of the special link between heroin and
cannabis claimed in Di Chiara's paper. Morphine
stimulates the same brain pathways, he points out.
Yet there is no evidence that the prolonged use of
clinical morphine makes people any more likely to go
out and abuse heroin.

For more about cannabis use, see this week's
editorial.