At least 90 percent of all alcoholics smoke. Why?

"All of the substances that are abused by humans," explainedneurochemist Joanna Fowler, "whether they be alcohol or nicotine,marijuana or psychostimulants like cocaine or the opiates, causeincreases in brain dopamine."

This neurotransmitter, she added, "is at the center of the reward andpleasure response regions in the brain. It's broken down by enzymescalled monoamine oxidases (MAO). So if you're drinking alcoholand getting your hit of your reward substance, dopamine, and you'realso smoking a cigarette, you may actually be accentuating thebehavioral effects of your alcohol."

Workers in the field of substance abuse, she observed, "speculate thatsmoking could be making another addictive or stimulant drug morerewarding, more pleasurable."

Fowler is director of positron emission tomography (PET) studies atthe Brookhaven National Laboratory in Upton, N.Y. PET technologyuses radioimaging and computer analysis to depict neurochemicalsystems in living tissues. To do so, it exploits the annihilation ofpositrons _ the opposite-charged counterparts to electrons. PET isthe most advanced instrument for probing neurochemical events invivo in the human brain.

Fowler is first author of a paper in the current Proceedings of theNational Academy of Sciences (PNAS), dated Nov. 26, and titled:"Brain monoamine oxidase A inhibition in cigarette smokers."

"We knew almost nothing of how smoke affects the brain," Fowlertold BioWorld Today, which is quite remarkable when you think ofthe public health problems linked to smoking. "And indeed," shecontinued, "we weren't even setting out to study smoking. But somesmokers crept in among our normal volunteers, and we found thatthese people had MAO levels that looked like they were on somekind of drugs."

That, she observed, "was a serendipitous finding, which set us off inthis direction. So we think the results of our just-published studymay be telling us something of help in developing cessationtreatments for smokers, and explaining some of the epidemiology."

Wanted: Health Smokers, Non-Smokers

To launch their investigation, Fowler's group last year placedadvertisements in various newspapers, including Brookhaven's ownhouse organ. These invited "healthy, normal volunteers to participatein a study of the effects of cigarette smoke on the human brain."

From a large number of responses, they recruited 31 subjects of bothsexes _ 16 smokers and 15 nonsmokers. The smokers had been oncigarettes for eight to 35 years, smoking up to two packs a day.

Because inhibitors of MAO are effective in antidepressant therapy,and cigarette smoke reportedly inhibits this enzyme, Fowler and herco-authors set out to test the hypothesis that the enzyme would belowered in the brains of smokers. PET imaging of their experimentalcohorts' brains showed that smoking correlated with a markedreduction of brain MAO .

"We found that the levels of MAO inhibition in the smokers' brainsamounted to a reduction of about 30 percent in enzyme activity," shesaid. "But if you give people MAO-based drugs to treat their clinicaldepression, you can inhibit around 90 percent."

Fowler pointed out that "the same neurochemical problems thatdispose a person to having depression may also predispose them tosmoking, to relieve depression. An alternative theory has it," shewent on, "that cigarette smoke contains a substance withantidepressant effects; that is, smokers are self-medicating."

She pointed to some studies "that suggest that an early episode ofdepression in adolescence is very highly correlated with futuresmoking behavior."

Attempted Cessation Heightens Blues

Fowler observed that "people prone to chronic depression are likelyto go through a major depressive episode when they try to stopsmoking."

At the neurochemical level, she pointed out, "Certainly, nicotine isthe addictive component of cigarette smoking. But there is somethingelse in the smoke, not nicotine, that inhibits monoamine oxidase."

Whatever that still-unknown component is in cigarette smoke, Fowlerobserved, "it could be something with therapeutic properties. It'scertainly conceivable, and highly probable," she added, "that you canseparate what people are perceiving as beneficial in the tobacco fromits toxic components."

These, she noted, "are the tars that cause cancer; the carbonmonoxide that promotes cardiovascular disease. The nicotine, whichis addictive, is also an anxiolytic _ it reduces anxiety, and helpsincrease alertness. Many pharmaceutical companies are trying todesign a drug," she said, " like nicotine, but non-addicting, to helppeople with alertness, anxiety, mood and memory."

Fowler concluded: "So it's likely that inhibition of MAO is abeneficial thing. But it comes about together with these very toxicother components. There's no way that cigarette smoking could comeclose to overall washing out as being beneficial."

Her paper made the relevant point that "there are approximately 1billion cigarette smokers in the world today, and about 3 million dieeach year from smoking-associated illnesses." n

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.