Marijuana's effects tracked in rat brains.

Regular exposure to marijuana, at least in rats, yields changes in brain chemistry that have been linked to the addictive effects of a number of other drugs, including alcohol, cocaine, and heroin, two independent studies find.

Long-term marijuana ingestion may subtly disrupt a reward system in the brain, increasing susceptibility to many other kinds of substance abuse, argues a team of neuroscientists directed by Fernando Rodriguez de Fonseca of Complutense University of Madrid.

Through its neurochemical effects, marijuana may even directly promote heroin use, concludes another group, headed by Gianluigi Tanda of the University of Cagliari in Italy.

Other scientists familiar with the new rodent findings, which appear in the June 27 Science, remain cautious about their potential for illuminating the nature of human addiction.

Rodriguez de Fonseca and his coworkers injected doses of cannabis--the substance from which marijuana and hashish are derived--into groups of three or four rats every day for 2 weeks. After 14 days of exposure to cannabis, the rodents received a drug that blocks cannabis activity and results in signs of withdrawal, such as salivation and compulsive grooming.

During withdrawal, the rats displayed sharp rises in the concentration of corticotropin-releasing factor, a chemical released in greater quantities from a particular brain structure in times of stress. Detailed analyses of the rats' brains also revealed that a group of stress-sensitive cells in the same structure, known as the amygdala, exhibits heightened reactions during withdrawal.

Similar withdrawal responses have been reported for rodents accustomed to receiving alcohol, cocaine, or opiates, the researchers note. The addictive pull of many drugs may depend at least partly on the mobilization of corticotropin-releasing factor by the amygdala and some related areas, they propose.

In the second study, Tanda and his colleagues gave rats doses of either heroin or tetrahydrocannabinol (THC), the active ingredient in marijuana. The two substances produced comparable increases in the amount of the chemical messenger dopamine in the outer layer of the nucleus accumbens. This area of the brain is located near the amygdala and may also stoke drug cravings.

Injections of two drugs known to block the effects of opiates stifled the neurochemical effects of both heroin and THC, the scientists say.

While marijuana activates specific receptors on brain cells, it also seems to arouse the same dopamine transmission system as heroin, they argue.

"Although our results do not provide direct evidence for a causal relation between [marijuana] and heroin use, they are nonetheless consistent with this possibility," Tanda's group concludes.

The new rodent studies show clear biochemical actions of marijuana, but their implications for people remain unclear, comments Michael J. Brownstein, chief of the laboratory of cell biology at the National Institute of Mental Health in Bethesda, Md.

In some earlier investigations, rats given cannabis declined further opportunities to receive the drug Brownstein notes. Cannabis-exposed rodents may experience unpleasant effects, making them unsuitable as a model for human marijuana users, he holds.

The new data support the suspicions of several researchers that the brain's dopamine system critically influences the reinforcing and addictive actions of many psychoactive drugs, says psychologist Rudy E. Vuchinich of Auburn (Ala.) University.

"These drugs have a profound effect on neurochemistry, but drug taking occurs in social contexts, in which many other factors influence consumption patterns," Vuchinich remarks.