1 MARCH 2007
SAN FRANCISCO - Experimenting with drugs is bad, of course -- unless you have a control group and conduct a proper statistical analysis. And since most people don't know a chi square from a square knot, their safest course of action is to steer clear from the substances that mess with their mental function.
Scientists, on the other hand, have been doing quite a bit of experimenting with
drugs, and they have some new insights to
report. Mainly, the latest findings
suggest that addictive drugs have been misunderstood. They are much more diverse
in their dangers than most people realized.
Popular belief from long ago insisted that drugs hooked their users by instilling a fear of the pain of withdrawal. But research eventually revealed that withdrawal symptoms were only part of the story. Drugs' allure came more from their power to produce pleasure, hijacking the brain's system of seeking rewards. Now, though, it seems that even the pleasure-reward explanation is too simple to explain all of addiction's power, says Nora Volkow, director of the National Institute on Drug Abuse.
It's true that addictive drugs provide pleasurable rewards, at least at first. But over time those drugs decrease the brain's sensitivity to the pleasure -- requiring more and more of the drug to produce the pleasurable effect. And that's not all.
"It has become evident that drugs not only affect the reward circuitry, but affect many more sites that are relevant to human behavior," Volkow said in San Francisco last month at the annual meeting of the American Association for the Advancement of Science.
Besides shorting out the brain's nerve cell circuits responsible for pleasure, drugs attack the circuits underlying motivation, driving addicts to seek their drugs in preference to behaviors needed to sustain a normal life. Another major assault occurs on the brain circuits responsible for learning and memory. Memories are stored by strengthening the connections (called synapses) between certain sets of nerve cells. Addictive drugs do a great job of strengthening the memory of their pleasurable effects. Strong memories of pleasure are evoked by the reminders of past drug use -- such as scenes or settings where the drugs were taken before.
Drugs also wreck the brain's mechanisms for making judgments and decisions. Drugs impair the ability to pay attention to what's important while filtering out distractions. Normal inhibitions against doing dumb things are diminished.
A spectacular example of a drug doing such damage is methamphetamine, which has rapidly overtaken cocaine and heroin as the archetypical evil addictive drug. Worldwide, a United Nations report says, meth use has surpassed cocaine and opiates combined.
Drug lore holds that meth actually boosts mental performance, and research suggests that it might, at first. But continued use reduces mental abilities. Meth appears, for example, to impair the anterior cingulate cortex, a brain structure important for controlling attention, Ruth Salo of the University of California, Davis and collaborators report, in a new paper to be published in the journal Biological Psychiatry.
And brain scans of meth users show that it damages critical brain regions, neuropharmacologist Edythe London of UCLA reported at the AAAS meeting. In particular, brains of meth users exhibit damage in the prefrontal cortex, the main brain region for higher-level thinking and planning, she said.
Meth also interferes with parts of the brain involved in emotion, particularly a small structure known as the amygdala. Meth 
users show loss of gray matter in the parts of the prefrontal cortex that send signals to the amygdala. "We see the amygdala essentially out of control and hyper-responsive," London said.
Photo: King County Public Health
All the multiple ways in which meth and other addictive drugs attack the brain seems at first to make the problem of abuse even more insurmountable than ever. But the new intelligence on addiction's tactics should actually help in designing counterattacks, Volkow pointed out. Researchers are now pursuing new strategies that might even make the "war on drugs" more than just a PR campaign.
For one thing, vaccination against abuse might be possible, by providing the body with antibodies that disable drug molecules or block their actions in the brain. Or medications may be devised that improve the brain's ability to inhibit drug-seeking behavior.
Volkow also remarked on evidence that exercising brain areas might improve their function. Biofeedback techniques, with the aid of brain scans, might offer a way to restore function to parts of the brain that drugs have disabled. "It allows you to train a person to actually learn to activate those areas of the brain that may not be functional," Volkow said.
Good drugs may also be enlisted to fight the bad drugs' strategy of tricking memory and learning to create a conditioned response to take the drug. "There are medications that can interfere with conditioned responses," Volkow pointed out.
More experiments and testing will be needed to develop these ideas into effective medical therapies. But some of the lessons have already been learned. For one thing, legal and moral considerations are far from the only reasons to beware of drugs of abuse -- there are powerful neurochemical considerations as well. From a scientific standpoint, it is clear, it's better for your brain to leave drug experiments to scientists.
E-mail: tsiegfried@nasw.org
