The Complex Dual Nature of Nicotine

This alkaloid can have toxic effects but research also finds it has therapeutic value.

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Smoking is undoubtedly one of the most dangerous habits a person can develop and one of the most certain ways to raise your risk for several serious diseases. And yet, if you strip away the hundreds of added chemicals in cigarettes and look only at nicotine, it appears this compound may have both toxic and therapeutic effects.

Nicotine is an alkaloid commonly associated with tobacco but also found in several foods we eat, and its character is more complex than you might imagine.

Consider evidence that suggests that nicotine may protect against COVID-19.

The idea challenges everything we’ve come to expect about nicotine, and its reputation for illness and addiction.

Smoking is often associated with cancer, but it has also been found to cause a lot of other diseases, such as stroke, heart disease, diabetes, and chronic obstructive pulmonary disease. In addition to stoking chronic illness, smoking can make you more vulnerable to infection and has been identified as one of the main risk factors in lung infections in particular.

So one can see why medical experts looked at COVID-19 as an opportunity to once again urge smokers to kick the habit. They cited past evidence showing that smoking weakens the immune system and preliminary studies that demonstrated that smokers who caught COVID-19 were more likely to suffer serious complications and require mechanical ventilation.

But as the pandemic wore on, some researchers found that just the opposite occurred as the population was exposed to SARS-CoV-2—the virus responsible for COVID-19. They showed that smokers were less likely to get sick and that those who did were less likely to suffer severe illness.

One such study, published in 2021 in the journal Frontiers in Medicine, found that the number of daily smokers among COVID-19 patients was “significantly lower” than the number of nonsmokers.

Researchers interviewed COVID-19 patients at a large French university hospital and found that only 0.24 percent of patients among the severe and fatal cases of COVID-19 were regular nicotine users (in the form of cigarettes, e-cigarettes, or some other nicotine-delivery method).

Another example comes from Heart, a publication by the British Medical Journal. This cohort study looked at 8.28 million participants and nearly 20,000 confirmed COVID-19 cases. It also showed lower odds for infection and COVID-related ICU stays associated with smokers.

Given the puzzling nature of these reports, some researchers have described this trend as the “smoker’s paradox.” It’s still not clear why it happens, but there are a few theories.

A meta-analysis published in a Polish journal in 2021 outlined some explanations. For example, since SARS-CoV-2 invades the body through its ACE2 receptors, some researchers suggest that nicotine reduces the amount of these receptors that the virus could exploit.

Another idea involved the interaction of SARS-CoV-2 with the body’s nicotinic cholinergic system. SARS-CoV-2 acts on this system in the body as COVID-19 develops. Nicotine, which is known to serve as a cytokine inhibitor, is believed to restore the function of the nicotinic cholinergic system and thus protect users from COVID-19’s dreaded cytokine storm.

Ironically, it’s the same nicotinic cholinergic system that may make smoking such a scourge. Nicotinic acetylcholine receptors (nAChRs) are found in various tissue types throughout the body and are responsible for a variety of biological functions. Many researchers believe abuse and addiction of tobacco is initiated when nicotine binds to nAChRs in the brain. 

However, it may not be fair to pile all the blame on tobacco. Some research suggests that several additives found in cigarettes contribute considerably to addiction. In 2014, researchers from Harvard University looked at one of these cigarette additives known as pyrazines. Researchers concluded that they “may enhance dependence.”

One examination found that more than 100 of the nearly 600 documented cigarette additives have pharmacological actions that camouflage the odor of tobacco smoke, enhance or maintain nicotine delivery, increase the addictiveness of cigarettes, and mask symptoms and illnesses associated with smoking behaviors.

Therapeutic Promise of Nicotine

Smoking is considered the most prevalent preventable public health problem in the world. According to the WHO Global report on trends in prevalence of tobacco use 2000–2025, smoking accounts for 9 percent of all deaths worldwide, and more than half of smokers die from smoking-related diseases.

And yet there is evidence that nicotine may have health benefits beyond protection from COVID-19.

A 2010 article from the British Journal of Addiction says that, in its pure form, nicotine has the potential to be a valuable pharmaceutical agent. Some positive associations with nicotine intake include weight loss, performance enhancement, and protection against diseases such as ulcerative colitis and sleep apnea.

“The reliability of these effects varies greatly but justifies the search for more therapeutic applications for this interesting compound,” researchers wrote.

Nicotine has also been shown to help with neurodegenerative disorders such as Parkinson’s and Alzheimer’s disease. Researchers have theorized that nicotine stimulates the release of a variety of neurotransmitters in the brain including catecholamines and serotonin, which are depleted in these diseases.

Poison or Remedy?

So is nicotine good for you or not? The answer isn’t so black and white. One study determined that nicotine exhibits neuroprotective effects and neurotoxic effects at the same time.

It’s clear today that smoking isn’t healthy, but 70 or 80 years ago, cigarette advertisements often included physician endorsements. One famous ad campaign proudly proclaimed, “More doctors smoke Camels than any other cigarette.” Back then, tobacco companies even advertised in medical journals and made a number of health claims about their product.

It’s tempting to think that this was a relatively short-lived delusion of the early to mid-20th century. But the idea of tobacco as medicine has been around a lot longer.

Although tobacco products are now found in most parts of the world, the plant is native to the Americas. Many native American cultures used tobacco in religious rites, but it was also used to address a number of health issues, including asthma, earaches, intestinal distress, fever, depression, insect bites, burns, and more.

Columbus first brought tobacco to Europe boasting of its curative properties. The word “nicotine” comes from Jean Nicot de Villemain, who introduced tobacco to the French court in 1560 as an herb that could treat a variety of ailments (including Queen Catherine de Medice’s migraines). However, Nicot’s influence did more to fuel a French snuff craze than to popularize new treatments. Early American colonists used tobacco as a form of currency.

But people also found fault with tobacco long before the first modern cigarette. When scientists first isolated the nicotine chemical from tobacco in the 1800s, it was deemed a poison. At higher doses, nicotine can be lethal.

But what about small doses? Consider all the nonsmokers who consume tiny amounts of nicotine every day. All plants in the Solanaceae, or nightshade, family, which includes eggplant, tomatoes, and potatoes, contain some nicotine, but in far smaller concentrations than tobacco.

So is there an ideal dose of nicotine? One that is large enough to produce a therapeutic effect, but small enough not to damage health or trigger an addiction?

Many substances used throughout history have been simultaneously classified as a dangerous poison and a valuable medicine, and the dividing line often hinges on dose.

In a 1938 journal article titled “Drug or Poison?” Dr. David I. Macht wrote that this dichotomy has been part of our understanding of medicine for a long time.

“The close relationship of medicament and poison is actually implied by our word ‘drug,’ which in its absolute sense denotes not only a remedy but also ‘dope.’ The Greek word pharmakon was similarly applied to both drug and poison,” Macht wrote. “The ancient Hebrews employed the word ’sam‘ for drug and also for poison and differentiated between the two by prefixing qualifying terms implying life or death. It was the sam, or ‘elixir,’ of life or the sam, or ‘elixir,’ of death. The Russian ’yad' has the same double meaning, and in other languages, the word for drug has a similar dual significance.”

Macht wrote that although dose is what often makes something either poison or therapeutic, there are other factors. A medicine for an adult, for example, can be a poison for a child.

With nicotine, this dividing line may be even more difficult to determine. In a 2023 article in the journal Bioelectronic Medicine that investigates the effect of pure nicotine on various cells involved in COVID-19, researchers note the complex character of this potential therapeutic.

“Current data indicates that smokers are more susceptible to some diseases and more protective of some others. Interestingly, nicotine is also reported to play a dual role, being both inflammatory and anti-inflammatory,” researchers wrote.