NEWSHAWK:  New Scientist
PUBDATE: July 5, 1997
CONTACT: 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.