Nicotiana tabacum
The tobacco plant, nicotiana tabacum, has been cultivated, chewed and smoked by the Native Americans since about 6000 B.C., possibly longer. For millennia, tobacco has been an important part of society, and used frequently for ceremonial and medicinal purposes. And yet today, we all know that cigarettes are responsible for hundreds of thousands of deaths every year in the US, as they are known to cause cancer, heart disease, lung problems, and more. They are expensive, and they are also heavily addictive- more so than cocaine and heroin.

One of the most active chemicals in tobacco is nicotine, which accounts for about 5% of the tobacco plant by volume. Nicotine is a naturally occurring liquid alkaloid, an organic compound made up of hydrogen, carbon, nitrogen and oxygen. One cigarette smoked has about 10 milligrams of nicotine in it.

Nicotine has a profound effect upon many systems of the body, including the brain and the adrenals. In light of the association between cigarette smoking and death, it is surprising that scientists have begun researching nicotine for its potential health benefits.

The Deadly Nightshade Family

Tobacco is a member of the deadly nightshade (or, belladonna) family of flowering plants, which also includes peppers, tomatoes, eggplants and potatoes. Throughout history, plants from the nightshade family have often been vilified or misused despite their medical benefits. This might be because plants in the nightshade family are filled with alkaloids that can have profound effects on the body.

Atropa Belladonna, also known as Deadly Nightshade, is one such plant that has offered medical and therapeutic benefits but can also be highly toxic, psychedelic and even lethal. Perhaps you remember the story on how Emperor Augustus of Rome was poisoned with belladonna by his wife? And yet, this poisonous plant has been used throughout history including in cosmetics and in herbal medicine as a pain reliever, muscle relaxer, anti-spasmodic, anti-inflammatory and to treat menstrual problems, peptic ulcer disease, and motion sickness throughout the 19th century. Currently, chemical derivatives from the plant are found in a host of medications including medications to dilate the eyes, anti-spasmodics, sedatives, and those for IBS symptoms.

Is Nicotine Harmful?

Conventional cigarettes bought and sold in the United States contain over 4,000 known chemicals including 69 known carcinogens such as radioactive polonium 210, formaldehyde, lead, benzene and arsenic. But where do these carcinogens come from? According to this report from the US Environmental Protection Agency (EPA), the radioactive material in the leaves of the tobacco plants grown in the US comes from the use of the phosphate fertilizers favored by the tobacco industry. As they spread phosphate fertilizers on the fields year after year, the levels of polonium 210 lead 210 rise and make their way into the tobacco plants. In other words…. According to the US government, it appears that the tobacco companies are to choosing to use cancer-causing radioactive methods to farm their tobacco.

But what if there was tobacco grown using different, cleaner methods? Would the nicotine still be harmful? Does nicotine itself cause cancer, or are cigarettes cancerous because tobacco plants are being poisoned with carcinogens? There does not appear to be an official government answer here. While US Centers for Disease Control (CDC) do label nicotine as a “toxic chemical,” they also note that “the information about nicotine as a carcinogen is inconclusive.”

One of the most respected researchers in the field, Dr. Paul Newhouse, Director of Vanderbilt University’s Center for Cognitive Medicine, argues that nicotineseems very safe even in nonsmokers. In our studies we find it actually reduces blood pressure chronically. And there were no addiction or withdrawal problems, and nobody started smoking cigarettes. The risk of addiction to nicotine alone is virtually nil.” Tobacco has also been considered harmful because it is highly addictive, but whether nicotine has the same addictive potential remains unclear. According to Dr. Newhouse, “nicotine by itself isn’t very addictive at all… [it] seems to require assistance from other substances found in tobacco to get people hooked.”

But, like other members of the deadly nightshade family, nicotine can be dangerous in high doses, and it is possible to die from overdose. There is discrepancy about how much one would actually need to ingest, ranging from the historically traditional amount of 60 mg up to as high as 1000 mg subcutaneously.

Nicotine affects many systems in the body, including the brain, pituitary hormones, sex hormones, thyroid hormones and adrenal functioning. This is not necessarily a bad thing, which is where the question of the harms of nicotine gets confusing. One the one hand, nicotine stimulates the body to produce an abundance of adrenal hormones, which can in turn lead to insulin sensitivity and put some people at risk for type-2 diabetes and heart disease. On the other hand, nicotine may also help heal the brain by stimulating neurotransmitters that can induce growth in cognition, memory and learning.

The new research into the potential medical benefits of nicotine has certainly been gaining momentum and seems worthy of further exploration. For example, some new research has shown that nicotine may provide pain relief, grow new blood vessels, and help treat Parkinson’s Disease, Alzheimer’s Disease, depression, schizophrenia and address other mental and physical health problems:

Pain Relief

Nicotine is a stimulant, but it interestingly seems to have calming, relaxing effect on the body. According to the World Health Organization, nicotine has been reported to reduce anxiety and pain, and nicotine users report that it improves their moods, increases pleasure, reduces anger and alleviates stress. However, researchers are unsure if it is the nicotine that is really improving people’s moods pharmacologically, or if it is the psychological effect of smoking and the perception of coping and calming down while smoking.

In terms of pain relief, the results are a little bit more concrete. Nicotine increases the number of neurotransmitters available in the brain, and so in response to nicotine, your brain increases the numbers of endorphins it produces. Endorphins are described as the body’s “natural pain killer” and they actually have a very similar chemical structure to the hardcore opioid painkillers like morphine

Blood Vessel Growth

While we know that nicotine may put people at risk for type – 2 diabetes, scientists are now discovering that nicotine may lead to new therapies for people with type -1 diabetes. Specifically, a study performed at Stanford University found that nicotine boosts the growth of new blood vessels. Ironically, the researchers began the study seeking to prove that nicotine damages the blood vessels, but they discovered the opposite

This could be useful to type-1 diabetes patients, who can lose limbs when wounds develop gangrene thanks to poor circulation. A company called CoMentis is now undergoing human clinical trials to test the efficacy of a low-dose nicotine gel on type-1 diabetes patients with chronic diabetic ulcers.

Parkinson’s Disease

In 1966, Dr Harold Kahn, an epidemiologist at the National Institutes of Health, began investigating the healing potential of nicotine after studying health data and noticing the statistical aberration that nonsmokers were at least three times more likely than smokers to die from Parkinson’s Disease. Why? Parkinson’s Disease (PD) is a degenerative disorder of the central nervous system. Nicotine stimulates the release of dopamine in the brain, the key neurotransmitter that appears to deteriorate in Parkinson’s Disease patients. The release of dopamine in the striatum part of the brain aids with the control of movements, helping to alleviate the shaking and tremors often associated with PD.

While animal studies have been conducted and there are plenty of anecdotal reports from PD patients who use nicotine to ease their symptoms, the first human clinical trial for nicotine as a Parkinson’s Disease treatment is currently underway for 160 adults with PD, sponsored by the Michael J. Fox Foundation . A 2014 article in Discover Magazine argues that nicotine has the potential to be the new Parkinson’s Disease “wonder drug.”

Alzheimer’s Disease

Alzheimer’s Disease is a degenerative brain disease that specifically affects memory, thinking and behavior. In America, 5 million adults over the age of 65 have Alzheimer’s, with a new person being diagnosed every 67 seconds. It also the 6th leading cause of death in the U.S. and 5th leading cause of death among people 65 and older. Nicotine, delivered either intravenously or subcutaneously, has been shown to improve cognitive tasks in people with Alzheimer’s disease, and even delay the onset of clinical dementia by reducing the rate of neurons lost in the brain.

Nicotine improves cognitive functioning by stimulating the release of neurotransmitters. In addition to dopamine, nicotine stimulates two very important neurotransmitters: Acetylcholine and glutamate. First, nicotine is chemically very similar to acetylcholine, meaning that it is able to bind with those receptors, and stimulate the neurons throughout the brain simultaneously. This creates heightened cholinergic pathways in the brain resulting in people feeling “re-energized.” Second, nicotine also stimulates the release of glutamate, a neurotransmitter that enhances connections between neurons and is involved in learning and memory.

In a double-blind 2012 study published in Neurology, 67 non-smoking older adults with MCI (Mild Cognitive Impairment, considered a median point between normal aging and dementia) were either given a 15 milligram nicotine patch per day or a placebo patch per day. After six months, adults who received the patch improved their age-adjusted ‘normal performance’ on long term memory tests by 46%, while the long-term memory test performance of the adults who did not receive the nicotine patch worsened by 26%.

Given the severity of Alzheimer’s and how traumatic it can be to see a loved one suffer from the disease, the notion that nicotine might be able to slow its progression and even reverse the cognitive decline associated with it could change many people’s lives.

Depression

Nicotine stimulates the activity of many neurotransmitters, which is why it can positively impact people suffering from depression and other mental health issues. Nicotine triggers the release of serotonin, dopamine and norepinephrine, all of which are implicated in depression. Nicotine may work by repairing the balance of these chemicals in the brain and facilitating their transfer between cells.

Interestingly, people with psychiatric problems purchase nearly half of all of the cigarettes in America, and the incidence is especially high among people with depression and schizophrenia. According to Dr. Ed Levin, nicotine researcher at Duke University, it is entirely possible that people with psychiatric problems are more likely to smoke because they are actually self-medicating with nicotine. In in 2012 alone, 16 million adults had at least one major depressive episode, meaning we are potentially talking about a huge population of self-medicating smokers.

At Duke University in 2006, 11 adults with depression were randomly assigned to wear either a nicotine patch or a placebo patch for eight days. Participants answered a 20-item questionnaire called the Center for Epidemiological Studies Depression Scale to measure their depression scores before and after wearing the patch for the duration of the study. Scores on the depression scale were reduced significantly in participants who wore the nicotine patch, but there was no change in those who wore the placebo. Researchers concluded that despite the small sample size, nicotine therapy was significantly associated with reduced depression.

Schizophrenia

Schizophrenia is a chronic, severe and disabling psychiatric brain disorder affecting about 1% of adults in the United States. In a large-scale study of 1,139 male patients with schizophrenia in China, smoking cigarettes was found to be consistently and significantly associated with reduced negative symptoms of schizophrenia.The same study also showed that men with schizophrenia were twice as likely as men without schizophrenia to smoke cigarettes.

Transdermal nicotine patches have also been shown to improve cognitive functioning in schizophrenic patients who do not smoke cigarettes.

Other Potential Therapeutic Benefits

Preliminary research has also supported the notion that subcutaneous nicotine can help to rectify the chemical imbalances implicated ADHD , and help control the involuntary muscle ticks associated with Tourette’s Syndrome. Researchers are also investigating if nicotine can help reduce ‘brain fog’ in patients who receive chemotherapy, if it can help to boost cognitive functioning in adults with Downs Syndrome, and if it can slow the cognitive decline of people with HIV.

New Alternatives to Smoking Cigarettes

Despite the promising benefits of using nicotine for a variety of therapeutic uses, scientists, doctors and researchers in the field are NOT encouraging their patients to smoke cigarettes! Remember, the tobacco in US cigarettes is farmed from irradiated fields and contains a number of known carcinogens. As Dr. Levin of Duke University said in 2007,When we can give people their medicine in a form that doesn’t kill them, it will be real progress.”

People seeking to experience cognitive benefits of nicotine do have some healthier options than smoking cigarettes. While it all started with transdermal patch and nicotine gum in the 1990s, now there are a variety of drugs being developed exactly for this purpose by companies like Targecept and CoMentis, that will probably be brought to market in the next few years. There is also relatively new invention taking the world by storm, the electronic cigarette or vaporizer pen, which allows users to inhale a liquid mixture of nicotine, propylene glycol or glycerol, and flavorings. These devices contain a battery or USB-charged heating element that warms up to vaporize the liquid, which may look clear or like smoke but is actually water vapor.

Are Electronic Cigarettes Less Harmful Than Regular Cigarettes?

Millions of people across the world now use e-cigarettes, and while it is too soon for any longitudinal studies on their effects, many scientific studies published in the last few years suggest that vaporizing nicotine is much less harmful than smoking it in cigarettes. According to one 2013 study that analyzed nicotine vapors from 12 different brands, their level of toxicants was anywhere from 9 to 450 times lower than toxicants found in cigarette smoke. A 2014 literature review entitled Electronic Cigarettes: Fact and Fiction alleges that the toxicity of nicotine vapor is nowhere near that of cigarette smoke, noting that the concentration of toxins in most vapors is below 1/20th of the level of toxicity in cigarettes. While the propylene glycol used to make some nicotine liquids may be an irritant, its toxicity concentration is also low.

In spite of the data clearly showing that e-cigarettes offer a much less harmful form of nicotine delivery than smoking, many organizations (such as the Word Health Organization) have rushed to warn the public of the dangerous of e-cigarettes. Even the city where I reside, Boulder, CO has proposed a ban on the use of vaporized nicotine in centrally located public spaces. If enacted, this policy would fly in the face of a 2014 report published in the International Journal of Environmental Research and Public Health stating that “e-cigarettes, even when used in no-smoking areas, pose no discernable risk to bystanders.”  Boulder CO is known internationally as a mecca for health conscious living, so it seems counter-intuitive for the city to go against science and punish residents who opt for the healthier alternative for their nicotine consumption (learn more on the proposed e-cigarette ban in Boulder, CO).

Bans on the public use of vaporized nicotine become especially problematic in light of the potentially profound benefits that nicotine may offer for many individuals who are suffering from debilitating mental and physical illnesses. Surely the pubic would want to embrace and support vaporized nicotine that does not harm bystanders but does help a citizen manage his Parkinson’s symptoms or treat her depression?

Nicotine Might Look Like The Next Miracle Drug… But More Research Is Needed.

Quite simply, people can be resistant to change and scared of things they do not understand. We are so inundated with the reality that cigarettes kill that perhaps as a society we have been closed off to the notion that in certain cases, nicotine can heal. Again, this isn’t the first time a plant with healing properties has been vilified until science proved its medical benefits. Just think about the 5 million people suffering from Alzheimer’s and the 16 million plus people suffering from depression, not to mention millions more with a host of other conditions that might benefit from nicotine therapy. But is nicotine the next miracle drug? Before we can say yes, we need more longitudinal studies, more clinical trials with larger sample sizes, and more research to determine the best practices for dosing and delivering therapeutic nicotine.