This is Your Brain on Drugs 2008

In public lecture, Alan Leshner argues for treatment for those with addictions

by Jim Schnabel

March 13, 2008

This is your brain on drugs: not the noisily frying eggs of the old TV scare-ad, but a complex mechanism with a short-circuit, compelled by its misprogramming to repeat the same dysfunctional actions again and again until it tears itself apart.

“Addiction is a brain disease expressed as compulsive behavior,” said psychologist Alan Leshner during a lecture on the science of addiction on March 4 at the Library of Congress in Washington, D.C.

Formerly the head of the National Institute on Drug Abuse, and now the CEO of the American Association for the Advancement of Science and a member of the Dana Alliance for Brain Initiatives, Leshner has long expressed a preference for the medicalization, rather than the mere criminalization, of addiction.

“People can very rarely will themselves out of being addicted, because of what drugs do to their brains,” he said. He compared the mix of biological, behavioral and social factors in addiction to those found in hypertension and diabetes, and portrayed the notion of a “war” on drugs as inappropriate. It’s “the worst metaphor,” he said. “It means ‘get out the cops.’”

How drugs hack the brain

“Your brain did not evolve for drugs,” Leshner said. “Your brain evolved for normal stuff.” Drugs effectively hack the brain’s reward-and-reinforcement system, he said, and “in all likelihood they rearrange your normal motivational priorities.”

Pleasure appears to be the brain’s reward to itself for having made the body do something “good”—in an evolutionary sense—such as having sex, eating nourishing food or caring for one’s children. The stimulation of its pleasure-centers by a given behavior also causes the brain to strengthen the connections that led to that behavior. The brain in effect signals to itself, "this choice was good, so keep choosing it."

This reward-and-reinforcement system depends heavily on a network of brain connections known as the “mesolimbic dopamine pathway.” Normally, when a person does something pleasurable, the neurotransmitter dopamine is pumped by this system into certain brain regions including the nucleus accumbens, frontal cortex and amygdala.

Unfortunately, modern chemistry confronts humans with an unprecedented number of compounds that can interfere with the inner workings of this system. Cocaine, for example, blocks the normal reuptake of dopamine from synapses in the mesolimbic pathway, thus boosting the activity at those synapses. Alcohol activates the mesolimbic system by binding to beta endorphin receptors on mesolimbic neurons. As Leshner pointed out, all addictive drugs somehow bring about sharp increases in the activity in this pathway. And every time they do, it seems, our brains automatically prioritize the preceding behavior— drug taking – a little more highly.

Ultimately, especially for people who have an extra vulnerability due to genetic or social factors, drug-taking ascends through the ranks of behaviors until it becomes more important, in the faltering brain’s calculus, than some of our most basic, healthy, sociable activities.

To illustrate, Leshner displayed functional magnetic resonance images (fMRI) from a study, reported in the American Journal of Psychiatry in 2000, by Hugh Garavan and colleagues at Trinity College, Dublin. In the study, a group of experienced cocaine users was asked to watch a film of people using cocaine, and then a porn film. The regions of their brains that were hotly aroused by the coke film showed relatively little response to the porn film—which was the reverse of the response seen in normal, non-cocaine-using subjects.

Such a rearrangement of priorities, to Leshner, is evidence of changes in our brains that mere cultural factors—moral persuasion, the threat of jail—cannot easily overcome. “It is a myth that people just stop,” he told his audience.

Addiction’s long shadow

Leshner also displayed brain-scan images from studies over the past decade that have shown how long it can take human brains to recover from addiction. In one case, a heavy cocaine user’s brain had failed to return to normal even after 100 days of abstinence. In another, a methadone user’s brain had not recovered after five months—with “a behavior change that persists” too, Leshner pointed out.

Addiction among other things causes the down regulation of normal, brain-produced pleasure-reward factors. The brain, like a thermostat sensing excessive heat, effectively dials down its own internal pleasure-production system, and even dials up opposing systems to maintain balance. Ultimately, a drug may be craved not for the euphoria it produces but just to maintain a feeling of normalcy. When such a drug is withdrawn, the brain has nothing to replace it with in the short term, and the brain’s owner can feel profound depression and strong cravings. Moreover, drugs often stimulate brain regions outside the pleasure centers, and the functions associated with those regions – such as learning and memory—are apt to be impaired too.

The brain’s recovery from chemical addiction can take years, and some brain systems may never recover. But downregulated brain systems are not the only legacy of long drug use. In the brains of drug addicts the motivational system, acting as evolution intended but subverted by drugs, sets up a network of “cueing” factors linked to drug-taking and the associated rush of pleasure. As Pavlov’s dogs learned to salivate at the sound of their usual dinner bell, addicts learn to expect their drug—and crave it—when cued by signals linked to their drug-taking.

For a heroin or cocaine addict, Leshner said, the cueing signal could be the mere “sight of the lamppost where they used to buy their drugs.” For a smoker, it could be the smell of the coffee that normally accompanies the first cigarette of the day. Leshner took pains to point out that in recovering addicts, cueing-induced craving can last far longer than actual chemical addiction. “The conditioned response stays almost forever,” he said.

What to do about addiction?

Treating addicts is a better strategy than not treating them, Leshner told his audience, citing more studies. In one, adolescents, after at least 90 days of drug treatment, were said to be about 50 percent less likely to resume the abuse of marijuana, alcohol or other drugs. Another showed, said Leshner, that “addicts put in jail without treatment have a 70 percent chance of being arrested within three years and a 30 percent chance of staying arrest-free—but if you treat them, you can flip those numbers.”

“It’s stupid not to treat criminals while they’re in prison because if you don’t treat them, they’ll be back,” he said.

Leshner has been making these points publicly ever since his stint at NIDA from 1994 to 2001, yet he told his Library of Congress audience that “the public has not gotten the message,” and suggested that changing public policy was “like nudging an elephant up a hill.”

Still, his advocacy of “a combination criminal-justice and health approach,” and a “whole patient” treatment strategy involving medication, behavior modification and social-environment changes was received warmly by his lunchtime audience.

Even one of Leshner’s long-time critics, Sally Satel, a psychiatric clinician and American Enterprise Institute fellow, declined to contest the idea that addiction involves long-term brain changes treatable with medication. “I work in a methadone clinic; I obviously believe in medications,” she said in a phone interview.

Leshner’s error, according to Satel, is his emphasis on the medicalization of addicts’ behaviors, which serves to weaken the belief that addicts have the capacity to change those behaviors. “This is where our best therapies are right now—in the behavioral domain,” she said.

Remarkably, given his doubts about the efficacy of willpower, Leshner admitted in his talk that he himself belongs to the small minority of ex-smokers—"three to seven percent”—who were able to kick the habit on their own. “In my case it was after nineteen attempts,” he said, although he also acknowledged that willpower, and behavior-based treatment, don’t yet have strong competition from pharmaceuticals.

“I am aware that there will never be a single medicine that solves addiction all by itself,” said Leshner. “It crushes me to know that, but it’s true.”