Don't count out potent nicotine Drug: Scientists are still penetrating the secrets of the most active of tobacco's ingredients.

Sun Journal

November 14, 1997|By Scott Shane | Scott Shane,SUN STAFF

A colorless, oily liquid used widely as an insecticide, it is fatal to humans in a large dose.

Yet nicotine's extraordinary power over the human psyche has shaped history. Export of that exotic New World weed Nicotiana tabacum turned Colonial America into a trading power. Later, nicotine's addictive grip helped build the cigarette industry into a commercial and political colossus.

Now the biochemistry of nicotine is a key to the lawsuits that have forced Big Tobacco to bargain with its foes. For 40 years, cigarette makers successfully defended suits by asserting that smokers freely chose their pleasure. That defense has faltered in the face of documents showing that tobacco companies long have worked to get smokers hooked as teen-agers, confident that nicotine would dictate their "free choice" as adults.

But whatever happens to cigarettes, don't count nicotine out.

As armies of lawyers skirmish in courtrooms across the country, scientists are still penetrating the secrets of the most active of tobacco's ingredients.

They are piecing together the mystery of addiction and tracking the drug's action in scans of the brain. They are beginning to think aloud about whether there might be a role for this drug or its chemical relatives in some kind of smoke-free future.

"Nicotine is an amazing chemical," says Jack E. Henningfield, a Johns Hopkins psychopharmacologist who studied it for years at the National Institute on Drug Abuse. He has been a prominent foe of nicotine and its peddlers for two decades, but he has a scientist's respect for its biochemical virtuosity.

Nicotine is contained in trace amounts in many plants, but vegetarians are unlikely to get addicted: They'd have to eat 100 pounds or more to get the nicotine in a single cigarette, Henningfield says. Scientists speculate that tobacco evolved to contain more nicotine because it conveyed a measure of protection from herbivores and pests.

In its natural form, nicotine causes a burning sensation in the mouth and throat, which might deter animals from grazing. To insects, even a tiny dose is poisonous, so the pure chemical is still used as a pesticide in many countries. Even in this country, farmers sometimes make a folk insecticide by soaking cigarettes in water.

Nicotine's affinity for the mammalian nervous system is such that turn-of-the-century scientists used the substance to map human physiology. Sir Henry Dale, a British physiologist, found in 1914 that nicotine mimics the effects of acetylcholine, a key neurotransmitter, one of the natural chemical messengers that carry nerve impulses.

To play this impostor's role in the body, nicotine has to reach the bloodstream. No vehicle carries it faster or more efficiently, Henningfield says, than tobacco smoke sucked from the 2,000-degree "micro blast furnace" of a glowing cigarette tip. The huge surface area of the lungs makes them an extraordinary absorption device, and the nicotine hits the brain within seconds.

Initially, the body reacts to nicotine as a toxin. To prevent the big doses from doing harm, it boosts the number of nicotine "receptors," microscopic bits of protein on nerve cells coded to latch with nicotine as a lock matches a key. Autopsies of some of the 425,000 Americans who die annually from smoking-related disease consistently show extra nicotine receptors.

These additional receptors, many scientists believe, play a role in addiction. Once the body is accustomed to a steady dose of nicotine, the nicotine receptors apparently either get their drugs or start making physiological trouble.

In a smoker deprived of nicotine, "rapid arithmetic skill declines after a couple of hours," Henningfield says. "Literally, their brain is starting to dysfunction."

At a National Institute on Drug Abuse lab in East Baltimore, scientists have observed the effect of nicotine addiction by using a PET scanner to watch brain activity. Smokers deprived ** of nicotine for 12 hours showed much greater brain activity during a memory test than nonsmokers.

"They're still accomplishing the task, but the brain has to work much harder to do it," says Edythe D. London, director of NIDA's brain imaging center.

Though she quit smoking more than 20 years ago, London says, her fingers still tingle when she discusses smoking. "The memory of drug-taking persists for an extremely long time," she says.

London emphasizes that nicotine is believed to play some role in smoking-related heart disease and says it would be "unethical and unwise" to offer nonsmokers nicotine products.

But some anti-smoking activists say nicotine is relatively safe if ingested without the carcinogenic tar cocktail smokers inhale. They say government regulation of nicotine products has been backward: Cigarettes have been virtually unregulated, while nicotine chewing gum and nicotine patches were subjected to costly testing and made available without prescription only last year.

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