Nicotine

Now that the tobacco industry has blinked, agreeing that cigarettes are a health hazard and discussing a $250 billion fund to pay for smoking-related illness, perhaps it's time to think about the unthinkable:

Suppose nicotine were good for you?

Behind the headlines is growing evidence that nicotine, the substance that makes tobacco addictive, may have some therapeutic effects. It's conceivable that future physicians might well prescribe nicotine -- as a drug, not a cigarette -- to relieve symptoms for a variety of diseases from schizophrenia and Alzheimer's to attention deficit disorder and colitis.

For the smoker, nicotine has a positive effect on attention, cognition and mood. Conversely, nicotine abstinence is characterized by uncomfortable psychological effects such as impaired attention, but also irritability. We postulated that nicotine exerts an effect on cerebral areas important for attention and mood. Regional cerebral blood flow (rCBF), as an index for cerebral activity, was measured in both smokers and non-smokers. They were scanned during performance of a psychometric task with and without i.v. infusion of nicotine (1-methyl-2-3-pyridyll pyrrolidine). Nicotine induced rCBF decreases in the anterior cingulate cortex and the cerebellum, and concomitant increases in the occipital cortex. The changes were similar in nature and magnitude in smokers and non-smokers. Thus, specific changes were induced in areas pertaining to the anterior attention system and to higher order visual cortex. We conclude that these effects on cerebral activity provide insights into the desired positive effects of nicotine on cognition as well as the negative effects experienced during nicotine abstinence.

Many cognitive skills decline with age, including short and long-term memory (Smith 1996; Zornetzer, et al. 1982). In rats, these deficits appear to be associated with neurochemical changes in the brain such as reduced levels of acetylcholine (Perry et al.
1992) and a decrease in the number of nicotine receptors (Court and Clementi, 1995). Deficits similar to these have been reported in patients suffering from Alzheimer's disease (Coyle et al., 1983) and suggesting that drug treatments that increase the levels of acetylcholine in the brain (cholinergic agonists) may be an effective treatment for this disease. The two cholinergic agonists currently approved by the FDA (Donepezil and Tacrine) have a limited positive effect on memory and have serious side effects (Sahakian and Coull, 1993). There is a need for the development of new drug treatments that are effective in counering the effects of aging on memory.

One possible cholinergic agonist with promising effect is nicotine. Nicotine agonists produce memory deficits in rats (Levin et al. 1997) and impair the neurological functioning of healthy humans in ways that mimic the early stages of Alzheimer's disease (Newhouse et al., 1992). The evidence in supprt of nicotine as a treatment for memory deficits is mixed. Some studies have found improvements in short-term memory but not
long-term memory in rats(Levin et al., 1993), while other have found the opposite (Arendash et al. 1995).