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June 21, 2005 - New York Times (NY)

Sometimes It's Better Just To Do Less Harm

By Richard A. Friedman, M.D.

Return to Drug War News: Don't Miss Archive

Hippocrates' injunction to physicians, "First, do no harm," is not always easy to follow. Sometimes doing the right thing medically means risking lesser harm to avoid greater harm.

When I first met Larry, he was 40 pounds overweight, hypertensive and in a bind. His internist had just told him that if he could not kick his two-pack-a-day smoking habit, he would surely kill himself.

His doctor was right, Larry said to me, but he also felt he could not live without cigarettes, either.

Larry had already tried to quit and failed four times in the last five years. Now, he was desperate to succeed.

The last time he supposedly quit, he was sneaking a cigarette on the porch in his bathrobe on a freezing winter morning so his wife would not discover that he had relapsed, when the door accidentally locked behind him. Shivering and chastened, he decided when his wife finally let him in that it really was time to quit.

But from our first meeting, I knew that his habit would be hard to beat. Every aspect of his waking life, from morning coffee to nighttime television, was entwined with smoking. And when he described the effects of smoking, he lapsed into a dreamy adoration usually reserved for lovers. He waxed eloquent about its relaxant and pleasurable effects, as well as the positive effects it had on his concentration and alertness. To me, he was a walking textbook on the pharmacologic effects of nicotine.

I wondered what therapy could even come close to such positive effects. A vast majority of medical therapies are intended to remove pain and discomfort, not replace a lethal pleasure with a healthier one. And patients accept treatments because, on the whole, they are better than the disease.

In contrast, the central challenge of treating any addiction is that the treatment is almost never as pleasurable as the addiction itself.

Like opiates and cocaine, nicotine is known to stimulate the release of dopamine in the reward pathways of the brain. This explains its pleasurable and powerfully self-reinforcing effects. Nicotine also releases an array of other neurotransmitters like serotonin, norepinephrine and vasopressin that mediate its other effects, like arousal, alertness and relaxation.

Anyone who doubts the addictive power of nicotine should reflect on the fact that 50 percent of smokers who have heart attacks continue to smoke.

One treatment for smoking addiction is bupropion, marketed as the antidepressant Wellbutrin, but also sold as Zyban for smoking cessation. Like nicotine, it increases dopamine transmission, but to a much lesser extent. It is thought to decrease the pleasurable effects of nicotine by pre-empting some of them.

Zyban seemed like a good option for Larry. But its cost, or the cost of any smoking-cessation treatment, for that matter, is generally not covered by health insurance. On the other hand, Larry's insurance would generously reimburse him if I wrote a prescription for Wellbutrin - same molecule, different name.

Because he was not depressed and felt that a record of having taken an antidepressant might be stigmatizing, he opted to pay out of pocket for Zyban, which proved minimally effective for him, anyway.

Larry was also using nicotine replacement in the form of nicotine gum and the nicotine patch. But they did not come close to matching the pleasing effects of cigarettes.

I decided to give him high-dose nicotine replacement, trying to outfox his smoking addiction. Only one form of nicotine replacement can approach the delivery system of a cigarette - nasal nicotine spray. Because it is absorbed rapidly into the bloodstream through the nasal mucosa, it produces a spike of nicotine in the brain, just as inhaled nicotine in tobacco smoke does.

Using more sprays than cigarettes, he was finally able to quit smoking. It has been more than a year since his last cigarette, but each month he calls me to renew his nicotine spray.

In the end, I simply switched Larry's nicotine system from lethal tobacco to a plastic spray bottle, but left his nicotine addiction untouched.

And though little is known about the very long-term risks of nicotine in humans, I wager that they pale next to the certain lethality of cigarettes. After all, it's the smoke that kills, not the nicotine.

Doing no harm is best, but sometimes harm reduction is as good as it gets.

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