The Demonization of Nicotine

Cigarette smoking is bad for you. If the financial power of the tobacco companies couldn't hide that fact from the public, then you know it must be true. More seriously, hundreds of studies have been done over the past century pointing the undeniable detrimental effects of cigarette smoking on almost every aspect of health.

It is also common knowledge that nicotine is the "active" ingredient in cigarette smoke and is the chemical responsible for addiction. It thus seems natural to attribute most (or all) of the dangers of smoking to nicotine exposure.

But this simply isn't the case. Rat models have repeatedly shown that nicotine is, by itself, weakly addictive. (1) But cigarettes undoubtedly are; so if not nicotine, then what is responsible for the addictive properties of cigarette smoke?

It turns out that cigarettes, in addition to tar and nicotine, contain a host of compounds with physiological activity. Two of these compounds, harman and norharman, have been singled out in addition to nicotine as key components of tobacco smoke. Both of these compounds, and a few others like them also found in tobacco smoke, inhibit an enzyme in the brain called monoamine oxidase B (MAO-B). (2)

MAO-B is responsible for breaking down and eliminating the neurotransmitters dopamine and phenethylamine (one of the main active ingredients in chocolate), as well as many other neurologically active molecules. Since dopamine is intimately connected to addiction (and pleasure) by means of its actions in the nucleus accumbens and ventral tegmental areas of the brain, it would be reasonable to expect that inhibition of MAO-B would make pleasurable substances and activities more pleasurable. And this is exactly what is seen for cigarette smoking.

It turns out that it is only the combination of nicotine MAO-B inhibition that results in addiction. (3) In other words, nicotine by itself is only weakly addictive because the body is able to regulate dopamine release in the brain by breaking down dopamine with MAO-B. Without MAO-B to retain balance, however, the dopamine release induced by nicotine leads to both the classic nicotine "high" seen with smoking and the consequent addiction.

Moreover, nicotine even has health benefits. It has long been known that smokers have lower rates of Parkinson's and Alzheimer's diseases, as well as reduced risk of inflammation-based disorders, including autoimmune conditions. These are likely in part due to the anti-inflammatory effects of nicotine, but recent studies have also shown that nicotine has direct effects on the brain that confer resistance to disease. (4)

At the end of the day, cigarettes are still as deleterious as they ever have been, but it's important to realize that nicotine itself is not really the culprit. Expect nicotine therapy as a proposed treatment for Alzheimer's, Parkinson's, and ADHD in the near future.

(1) Bozarth, MA et al., Effect of chronic nicotine on brain stimulation reward. I. Effect of daily injections, 1998

(2) Pfau, W, et al., Exposure to beta-carbolines norharman and harman, 2004.

(3) Guillem, K et al., Monoamine oxidase inhibition dramatically increases the motivation to self-administer nicotine in rats, 2005

(4) Akinoi, A. et al., Mechanisms of Neuroprotective Effects of Nicotine and Acetylcholinesterase Inhibitors: Role of alpha4 and alpha7 Receptors in Neuroprotection, 2009