Cigarette smoking may have effects on the human brain similar to those of antidepressant drugs, and this may explain the high rate of smoking among depressed people and their resistance to quitting.


Researchers have noted previously that depressed people are more likely to smoke and are more resistant to quitting. However, it was unclear if nicotine or other chemicals taken in during smoking directly affected the brains of people who were depressed.


In a new study Dr Gregory Ordway, professor of psychiatry at the University of Mississippi Medical Center, and colleagues examined postmortem samples of locus caeruleus from the brains of seven people who had been heavy smokers and nine who had been non-smokers; all had been mentally healthy. They found that the brains of long term smokers had neurochemical abnormalities similar to the brains of animals treated with antidepressant drugs (Archives of General Psychiatry 2001;58:821-7).
Specifically, the brains of longtime smokers had significantly fewer a -2 adrenoceptors and significantly less of the enzyme tyrosine hydroxylase, which helps to manufacture the brain chemicals noradrenaline and dopamine. These two effects have been reported in animals exposed to antidepressant drugs and are two of the markers used to identify potential antidepressant drugs.


"This may contribute to the high incidence of smoking and difficulty to quit in those who are depressed," Ordway said.


Nicotine's action on the reward system has long been believed to produce drug induced feelings of pleasure and, over time, addiction. Nicotine also has the effect of increasing alertness and enhancing mental performance. In the cardiovascular system, nicotine increases heart rate and blood pressure and restricts blood flow to the heart muscle. The drug stimulates the release of the hormone epinephrine (adrenaline), which further stimulates the nervous system and is responsible for part of the "kick" from nicotine. It also promotes the release of the hormone b endorphin, which inhibits pain.


It is still unclear whether smoking causes the antidepressant effects that researchers observed, or whether people with the relevant brain chemistry are more susceptible to becoming smokers. Ordway said he suspected that smoking does cause these neurochemical changes, and he plans to conduct additional studies on animals to find out.


The findings might help to explain the effectiveness of a drug recently approved by the Food and Drug Administration as an aid for quitting smoking, the antidepressant buproprion. Paradoxically, buproprion is more effective for treating nicotine addiction in non-depressed smokers than in smokers who are depressed.



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