Injury shuts off urge to smoke

Stroke damage to site deep in brain eliminates desire, researchers find

January 26, 2007|By Michael Stroh | Michael Stroh,Sun reporter

In a finding that could lead to powerful new treatments for smokers unable to quit, scientists have discovered that people who experienced stroke damage to a prune-sized spot deep within the brain suddenly lost the urge to light up.

The research, published today in the journal Science, underscores nicotine's far-reaching grip on a smoker's neural circuitry -- and how much there remains to learn about it. Until now, addiction researchers have largely ignored the brain structure implicated in the study -- a region called the insula.

"It's a really tremendous paper, one that points us in a whole new direction," says Steven Grant, who is chief of the clinical neuroscience branch of the government's National Institute on Drug Abuse and was not involved in the study. "It says: This is a brain area the addiction field needs to focus a lot of attention on."

While intentionally inflicting damage to a smoker's brain is ethically out of the question, scientists said it might be possible to mimic the effect of insula injury with drugs or other therapies. Such treatments could also help people addicted to chemicals other than nicotine, researchers said.

In the study, researchers at the University of Southern California and University of Iowa looked at 69 smokers with various brain injuries, mostly as the result of a stroke. All the participants had smoked at least five cigarettes a day for two years or more.

Of 19 smokers whose insula had been damaged, 13 almost immediately stopped smoking, researchers found. One of the most striking cases was a 38-year-old mathematician, identified as "Patient N."

A smoker since the age of 14, the man typically inhaled more than 40 unfiltered cigarettes a day -- his final one on the evening before his stroke.

But when he woke up in the hospital, his nicotine cravings had disappeared. "My body forgot the urge to smoke," Patient N told researchers.

"His quitting was completely effortless, like a switch going off," says Antoine Bechara, a researcher in USC's Brain and Creativity Institute and senior author of the report.

Patient N even became so disgusted by the smell of his hospital roommate, who frequently left the building to smoke, that he asked to change rooms.

Researchers were at a loss to explain what's going on in the brains of Patient N and the other quitters. Another mystery: why six of the insula-damaged subjects did not quit smoking.

Part of the difficulty is that little is known about the insula, although scientists say it's one of the brain's most ancient structures.

As best they can determine, the region plays a role in basic survival, translating signals from various parts in the body into visceral sensations, including hunger pangs and pain.

Brain imaging studies have also linked it to drug cravings, although few researchers paid attention to the finding.

This study, researchers said, is the first to probe nicotine addiction through the prism of brain damage. But the results fit with what scientists have learned from brain imaging and autopsy research in recent years.

Jack Henningfield, a professor of behavioral biology at the Johns Hopkins School of Medicine, says chronic tobacco exposure leads to changes in the "structure and function" of the brain: "In other words, quitting is not just will power against the desire to smoke. Quitting smoking is a battle with the biology of the brain."

This, he says, helps explain why, of the more than 44.5 million smokers in the United States, fewer than 5 percent succeed in quitting long-term.

Drug companies seeking new anti-smoking therapies are racing to exploit the emerging understanding of how nicotine behaves in the brain.

Last May, the Food and Drug Administration approved Pfizer's varenicline, sold under the trade name Chantix. It stimulates the production of dopamine, the feel-good hormone that surges through brain tissue in response to behaviors such as eating, sex and smoking tobacco.

By artificially upping dopamine levels in the brain, Chantix blunts nicotine cravings and other withdrawal symptoms. It also makes smoking less satisfying by preventing receptors from absorbing nicotine.

That's the theory, at least. And an independent review, by the British-based Cochrane Collaborative, of the clinical evidence on Chantix released last month seems to back it up: The drug was three times more effective than a placebo in helping people to quit.

Other novel therapies are also in the works.

The FDA is closely monitoring clinical trials of NicVax, a vaccine developed by Florida-based Nabi Biopharmaceuticals that trains the body's immune system to attack nicotine like a foreign invader. The hope is that by doing so, it will prevent the chemical from reaching the brain in the first place.

Sanofi-Aventis, meanwhile, is seeking FDA approval for rimonabant, a weight-loss drug currently available only in Europe. The drug, sold as Acomplia, appears to interfere with another nicotine reward circuit in the brain and thus prevent cravings.

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