The Year in Science: Brain 1997

Better not inhale

By Sarah Richardson|Thursday, January 01, 1998
Nobody disputes that marijuana is mind-altering. But is it a harmless herb or a step down the slippery slope of drug addiction? Two reports, both published in Science in June, throw a sinister light on the funny cigarettes. In these studies of rats, researchers turned up evidence that marijuana produces the same biochemical changes in the brain as heroin, cocaine, or, for that matter, nicotine and alcohol.

A common feature of addictive drugs, explains Italian pharmacologist Gaetano Di Chiara, is that they prompt release of the brain chemical dopamine in the outer layer of the nucleus accumbens, a thimble-size region in the limbic forebrain. This outer layer, he adds, is involved in regulating motivated behavior, such as mating, eating, fighting, and mothering. When Di Chiara and his colleagues at the University of Cagliari gave the active ingredient of marijuana intravenously to rats, they found that it, too, prompted dopamine levels in the nucleus accumbens to rise—just as, say, an injection of heroin would.

Moreover, the researchers found they could prevent either marijuana or heroin from releasing dopamine with a drug that blocked only the heroin receptors on the rats’ brain cells. That suggests, says Di Chiara, that marijuana interacts, directly or indirectly, with heroin receptors as well as with the ones that are specific to it, so it could well prime the brain for stronger stuff. Epidemiological studies show frequent marijuana use to be a risk factor for heroin use.

Still, giving up marijuana doesn’t produce as strong a withdrawal syndrome as other addictive drugs do—but that may be because the drug is slow to leave the body. In the second study, researchers produced a pot version of cold turkey by giving synthetic marijuana to rats for two weeks, followed by a compound that quickly blocked the marijuana receptors. The team, led by neurobiologist Fernando Rodríguez de Fonseca at Complutense University in Madrid, found that the rats became stressed—they fidgeted and groomed themselves nervously. Meanwhile their amygdala, a brain region that regulates emotional responses, released large amounts of a brain stress hormone. Rats abruptly taken off heroin experience similar effects.

Neither study shows, though, that the two drugs are equally addictive. It is likely that there is a big difference between intravenous heroin and marijuana, says Di Chiara, but this is not because the two substances are so different from the point of view of impact on the brain. One possibility is that the difference is just a question of the amount and means of administration.
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