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A dangerous pathway...

New Scientist, vol 155, issue 2089 - 05 July 97, page 4

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 opioid-like 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.

* * *

Who's on what?

  • Almost 5 per cent of Americans use cannabis at least once a month
  • Alcohol is used by 52 per cent and tobacco by 29 per cent
  • The figure for heroin is less than 0.1 per cent

David Concar