How to Get Monkey Off Your Brain

The result is euphoria for the user, but the brain is overwhelmed and tries to dampen the effect by switching off some of its dopamine receptors. Consequently, when the drug wears off, the user is equipped with fewer functioning receptors, so his mood will be lower than it was before he took the drug. Thus begins the negative feedback loop that leads to addiction. As dopamine receptors progressively shut down, drug users must ingest ever larger quantities in order to get high, and will feel increasingly unhappy when the drug leaves their system. Eventually, cocaine effectively becomes the puppeteer of much of the dopamine levels in the brain. Users may need to take drugs simply to feel a normal amount of well-being. Some recent research indicates, however, that when addicts stop doing drugs, the disabled dopamine receptors in their brains can repair themselves.


Through dissections of animal brains, scientists had shown that the dopamine pathway responds similarly to all habit-forming drugs. But in 1997 Nora Volkow, Brookhaven's associate laboratory director for life sciences, harnessed an emerging technology, positron emission tomography (PET), and became the first scientist to demonstrate the addiction mechanism in living people. PET scanning is a noninvasive method of observing the brain in real time. Volkow employed it and oral interviews to study 17 long-term cocaine users, and found that as the number of engaged dopamine receptors in the brain increased, the subjective experience of feeling high did too. "Volkow is very good at looking at systems we're pinpointing and, with imaging, answering questions we haven't been able to answer," says Roy Wise of NIDA.


Volkow's colleague, Stephen Dewey, made critical use of the results of this study. Aware that an epilepsy pill called Vigabatrin works in part by lowering the amount of dopamine in the brain, Dewey wondered whether the medication might also be helpful for cocaine addiction. He injected Vigabatrin into half of a group of baboons, then studied the brain scans of the entire group both before and after they ingested cocaine. In the Vigabatrin-primed baboons, the cocaine did not increase the amount of dopamine activity in the brain. The animals that had not been given the epilepsy drug, meanwhile, showed a marked increase in the level of dopamine attached to receptors. In people, of course, Dewey hopes Vigabatrin will do more than keep dopamine activity from rising with cocaine use; he hopes Vigabatrin could banish the craving for cocaine altogether. The drug's manufacturer is in negotiations to launch a study to test Vigabatrin with addicts.


An interesting result of Dewey's studies is what he unexpectedly revealed about the so-called cueing response-the desire to drink or take drugs that's sparked by familiar sights and sounds, such as the tinkling of ice in a scotch glass or the scratch of a razor against a mirror. Scientists traditionally believed that these responses were fundamentally behavioral. Recovering addicts were counseled not to rejoin friends in the old neighborhoods where their drug habits began, or risk relapsing.