Nicotine is highly addictive, but some scientists think we need to distinguish between the effects of nicotine and the effects of cigarettes. Smoking is certainly a killer, but how does nicotine affect the body and why are some researchers interested in it? Read on to find out.
Disclaimer: As a medication, nicotine replacement therapy can help people stop smoking. However, we are not recommending the general use of nicotine by writing this post. If you want to quit smoking, talk to your healthcare provider about the best options available for you. Stop-smoking programs should also include counseling and additional support. The aim of this post is to summarize some data from the scientific literature for purely informational purposes.
What is Nicotine?
Nicotine is an addictive substance that naturally occurs as a liquid alkaloid in many plants of the nightshade family. Tomatoes, potatoes, eggplant, and tobacco all contain nicotine .
Nicotine is what gets people addicted to cigarettes. Scientists view it as the initial trigger, though it plays a minor role in causing smoking-induced diseases like cancer, heart disease, and lung disease. These diseases result from exposure to toxins in tobacco smoke .
Tobacco and tobacco smoke contain a dangerous mixture of thousands of chemicals [2, 3].
But simply put, people would probably never inhale cigarette smoke if it wasn’t for nicotine. Nicotine is what gets people hooked – and it’s what keeps them hooked [2, 3].
According to a recent scientific review, cigarette smoking remains a leading cause of preventable disease and premature death in the United States and other countries. Lifelong smokers have about a 50% chance of dying prematurely from a complication of smoking .
Addiction & Getting Help
According to the FDA, using any tobacco product that contains nicotine can lead to nicotine addiction .
The following products all contain nicotine:
- Smokeless tobacco (used by other means than smoking)
- Hookah tobacco
- Most e-cigarettes
Having these dangers in mind, we highly advise against smoking or using tobacco. If you are a smoker, seek professional help as soon as possible. Stopping smoking is among the most important things you can do to improve your health and longevity.
Additionally, no e-cigarette has yet been approved as a cessation device or a modified risk tobacco product, which are products that present lower health risks to people compared to existing products. More research is needed to understand the effects of e-cigarettes on addicted adult smokers .
Nicotine Replacement Therapy
When used appropriately, nicotine replacement therapy can help people stop smoking. It poses the lowest risk to health among all nicotine-containing products. Nicotine replacement therapy is available :
- By prescription as oral inhalers and nasal sprays
- Over-the-counter for adults age 18 and over as skin patches, lozenges, and gum
Consult your doctor or pharmacist for any questions about using these products for smoking cessation
People have the best chance of success when they are ready to commit to the decision to quit. Smoking cessation programs usually also include counseling, behavioral therapy, and support.
Why Study Nicotine?
This section summarizes the existing experimental human, animals and cell-based research on nicotine and nicotine-related targets. The aim of the existing research is to guide further investigational efforts.
Scientists are interested in nicotine because it helps them understand the pathways of reward and addiction in the brain. They are also studying so-called nicotine receptors, to which many substances aside from nicotine can bind to.
Some researchers are examining the effects of special nicotine formulations on cognition. On the other hand, certain drug companies are interested in various nicotine-related compounds. These nicotine-like compounds are undergoing early trials for ADHD, schizophrenia, and as anti-smoking pills.
Despite ongoing research efforts, no nicotine-related drugs are on the market yet since their benefits and risks have not been established in large-scale trials.
Research on nicotine-related pathways and compounds is still in the early stages. The studies listed below should not be interpreted as supportive of any health effect.
Mechanism of Action
Scientists suspect that other compounds in tobacco interact with nicotine and act as monoamine oxidase inhibitors (MAOI). In one rat study, this likely increased the animals’ motivation to self-administer nicotine. The authors hypothesize that this mechanism may underlie the intense reinforcing properties of cigarette smoking that lead to addiction [4, 5].
Additionally, MAOIs prevent the breakdown of neurotransmitters like dopamine, serotonin, and norepinephrine in certain areas of the brain, increasing their levels.
Nicotine activates nicotinic acetylcholine receptors. Cells studies suggest that acutely, it mimics the effects of acetylcholine in the brain. Chronically, however, it may have the opposite effects. Researchers believe that long-term nicotine may cause long-lasting changes in the nervous system by, in part, disabling nicotinic cholinergic signaling .
Nicotinic acetylcholine receptors are found in different brain regions, including the thalamus, occipital cortex, and cerebellum. Nicotine can act on various subsets of nicotinic receptors, including alpha-4, beta-2, and alpha-7, the exact effects of which are an area of research [7, 8].
Some investigators suggest that nicotine can also indirectly increase dopamine in parts of the brain, which also likely causes reinforcing effects and dependance [9, 10].
Areas of Research
Experts and scientists agree that although nicotine may not clearly be a carcinogenic substance, it may be a “tumor promoter” or a compound with “angiogenic properties” [11, 12].
Angiogenesis is the process of new blood vessel growth. So-called pathological angiogenesis is what may contribute to cancer and heart disease, according to some studies [11, 12].
According to other recent studies, nicotine may affect several important steps in the development of cancer. Scientists have suggested that it may increase the likelihood of cancer worsening and recurrence .
These findings have discouraged any kind of research with nicotine and nicotine-related compounds.
On the other hand, the growth of new blood vessels and red blood cells might be beneficial in some specific cases, such as wound healing and stroke recovery. In this sense, some scientists have compared the double-edged effects of nicotine pathways to IGF-1 [14, 15].
The unresolved question, however, is whether the potential benefits of experimental nicotine-related compounds can outweigh their potential dangers. We don’t have any definitive answers yet, but future clinical trials should provide us with some clues .
Addiction & Withdrawal
It’s a well-known fact that nicotine is addictive. Quitting tobacco/smoking can lead to withdrawal syndrome 4-24 hours after stopping .
Withdrawal symptoms may include strong cravings, increased appetite, sleep disturbances, gastrointestinal problems, anxiety, anger, frustration, depression, irritability, and restlessness. Symptoms usually subside within 3-4 weeks .
Many complex brain pathways are involved in establishing and maintaining nicotine addiction and tolerance. Nicotinic cholinergic receptors that are initially activated start becoming less sensitive. Scientists say that this process of desensitization leads to tolerance and dependence .
Desensitization is also likely what triggers withdrawal symptoms and cravings when people try to quit. According to this theory, the main biological reason long-term smokers continue using cigarettes is to avoid the unpleasant process of withdrawal .
Some scientists suggest that whole short-term use of nicotine can have anti-anxiety and antidepressant effects, which may be why some people “self-medicate,” but that chronic use can increase anxiety and depression .
Some studies suggest that nicotine may be a promoter of increased capillary blood vessel growth. Cigarettes contain various chemicals that cause smoking-induced diseases like cancer, heart disease, and lung disease. In cells, nicotine has been shown to increase tumor growth in colon, pancreas, breast, larynx, and lung cancer cell types [2, 18, 19, 20, 21, 22].
Some scientists suspect that nicotine may increase the progression and growth of tumors initiated by tobacco carcinogens. Mice treated with nicotine had a nearly 40% higher tumor recurrence after initial tumors were successfully removed. These effects were not explored in humans due to safety concerns and the addictive properties of nicotine .
Brain Development in Adolescents
Scientists found that nicotine impairs the prefrontal cortex – a part of the brain implicated in planning complex cognitive behavior and decision making – in adolescent users 
Cigarette smoking and/or nicotine ingestion could impair the development of the prefrontal cortex region of the brain in users under the age of 25 .
According to some studies, nicotine use during adolescence increases the risk of cognitive impairment later in life .
Adolescent nicotine use has been associated with a later risk of developing mental and behavioral problems such as depression, agoraphobia, panic disorder, and antisocial personality disorder .
Scientists are also investigating the effects of nicotine on estrogen and inflammation in the brain .
Risk of H.Pylori
Limited research suggests that H. pylori infection is more common in smokers and eradication therapy less effective. Researchers consider that nicotine may increase the toxin activity of H. pylori in the stomach .
Wakefulness & Motivation
Research suggests that nicotine can significantly change electrical activity in the brain [26, 27].
Nicotine is known to have stimulant and arousing effects. Limited imaging studies suggest that these effects may be caused by increased alpha(2) and beta brainwaves [26, 27].
Acutely, nicotine activated orexin in rats. It’s unknown whether it affects orexin in humans .
Transdermal nicotine replacement therapy increased task-based brain activity in areas associated with visual attention, arousal, and motor activation. The authors explained that their findings may help explain both its addictive properties and therapeutic potential .
Imaging studies suggest that nicotine increases activity in the following regions of the brain: parietal cortex, thalamus, caudate, and occipital cortex .
Memory & Fine Motor Skills
One aspect of nicotine withdrawal is difficulty concentrating. Scientists proposed that nicotine’s cognition-increasing effect is one of the reasons why people start smoking and go on to maintain tobacco dependence. According to some studies, smokers report that the “perceived cognitive benefits of nicotine” are among the reasons they smoke.
However, the scientific accuracy of such claims remained unproven until recently. New meta-analyses suggest that nicotine can affect the following areas of cognitive functioning [31, 32]:
- Fine Motor Skills
- Alerting attention – accuracy and response time
- Orienting attention – accuracy and response time
- Short-term memory – accuracy
- Long-term memory – accuracy
- Working memory – accuracy and response time
The authors suggested that nicotine and nicotinic agents should be studies in cognitively impaired populations .
Scientists are investigating the effects of nicotine on attention-related tasks, processing speed, multitasking ability, and vasopressin pathways in clinical and experimental animal studies [33, 34, 7, 35].
However, we are still far from a nicotine-based medication for people with cognitive problems due to efficacy, safety, and addiction concerns.
In low-quality, small-scale studies dating back to the ‘90s, acute nicotine treatment reduced the severity of clinical symptoms and increased attention in patients with ADHD. No proper clinical trials have verified their findings nor have any studies described the effects of chronic nicotine exposure on ADHD [36, 37].
In one case report, a nicotine patch was helpful for an ADHD patient with anxiety and depression who was a recovering ex-smoker and wanted to stay tobacco-free .
Alzheimer’s and Parkinson’s
Controversial studies suggested a link between smoking and lower incidence of Parkinson’s and Alzheimer’s disease. However, these studies dealt only with associations and no cause-and-effect relationship can be established [39, 40].
Additionally, smoking has been linked with both increased and decreased Alzheimer’s risk. Most likely, toxins in cigarette smoke damage blood vessels in the brain and increase the likelihood of Alzheimer’s-like brain changes [39, 40].
Some scientists are further investigating the effects of special nicotine formulations on cognition and motor function in Alzheimer’s, Parkinson’s, and schizophrenia [41, 33, 32, 34, 39].
Early research suggests that, acutely, nicotine may increase processing speed in Parkinson’s patients. Nicotinic agonists are being developed and investigated as potential add-on therapy, but no conclusions can be drawn before large-scale studies are carried out .
In animals, scientists looked at the effects of nicotine on brain damage in dopaminergic pathways typically associated with Parkinson’s. They suggested that nicotine’s stimulation of nAChR (nicotinic acetylcholine receptors) may play a role in preventing age-related and neurodegenerative mental decline. Yet their hypotheses remain unproven [39, 34, 42, 43, 44].
Among the numerous negative health effects of smoking is its so-called interference with ulcerative colitis.
Limited studies have suggested a link between ex-smokers and increased ulcerative colitis risk, as well as between smokers and decreased ulcerative colitis risk. Since smoking is a major worldwide cause of death, the risks of smoking far outweigh any possible benefit in people with ulcerative colitis .
Nonetheless, some scientists think that investigating nicotine as a potentially therapeutic substance in ex-smokers with ulcerative colitis might be worthwhile. On the other hand, high-quality studies have failed to verify most associations between smoking and a less severe ulcerative colitis disease course .
Some researchers label nicotine as an “anti-inflammatory alkaloid.” They believe that nicotine may acutely suppress inflammation by acting on vagal nerve pathways (also known as the cholinergic anti-inflammatory pathway), based on animal studies. The short- and long-term effects of nicotine on inflammation in humans is still unknown [47, 48].
Scientists have explored the effects of nicotine or nicotine agonists on the following pathways in cell culture or animals:
- Cells’ responsiveness to the pro-inflammatory cytokine TNF-α .
- IL-2 (Th1 cytokine) and TNF-α production (in blood cells) .
- IL-1ß and TNF-α concentrations in colonic tissue in mice .
- Nicotinic receptors in rheumatoid arthritis .
- Interacting with bacterial lipopolysaccharides (LPS) via nicotinic receptors (α7 nAChRs) .
- Beta-amyloid accumulation and episodic memory decline .
Limited studies looked at blood cells from smokers. They have suggested that smoking causes irregular cytokine profiles in people with Crohn’s disease, ulcerative colitis, and other inflammatory bowel diseases, possibly due to nicotine .
A liquid enema containing 5 mg nicotine (+ carbomer) per 100 ml has been studied as an add-on to conventional therapy in the treatment of ulcerative colitis. Its safety and efficacy remains unconfirmed .
Scientists are investigating whether nicotine increases acid and pepsin secretions, gut motility and bile secretion . Some studies suggest that nicotine reduces the transit time from ingesting food to bowel movements . Another old study mentions that nicotine delayed emptying of contents in the stomach .
In one small, low-quality study of women conducted after gynecological surgery, those given access to morphine + nicotine scored their pain lower than women who were given morphine + placebo. We can’t draw any conclusions from a single human study with major design flaws .
Animal research suggests that nicotine suppresses appetite. Researchers are looking at its effects on the following in cells or animals :
- Obesity .
- Hunger, POMC neurons, and melanocortin MC4R receptors .
- Blood sugar balance and insulin sensitivity .
It’s unknown how nicotine affects tissue repair in humans. In mice, low concentrations of topically applied nicotine promoted wound healing [60, 61].
Preclinical research suggests that nicotine increases the growth of tissues and blood vessel capillaries (vasculogenesis and angiogenesis), which has also been linked to cancer risk. On the other hand, scientists are wondering if certain nicotine topical formulations can repair damage to blood vessels and increase blood circulation. More research is needed [18, 14].
Limited data suggests that nicotine might help improve cognitive related symptoms in those suffering from schizophrenia. Its safety and efficacy in this population has not been established .
According to some theories, nicotine is believed to help to stabilize chaotic dopaminergic activity in people with schizophrenia [62, 10].
Additionally, 80% of people with schizophrenia smoke compared to 25% of the general population. It has been proposed that smoking is a form of “self-medication” for people who suffer from schizophrenia .
Some scientists are looking to determine people with schizophrenia are more genetically predisposed to the cognitive effects of nicotine [63, 10, 58].
Several research teams are investigating the effects of nicotine as an add-on to traditional drugs in people with Tourette’s. In a small study, nicotine patches were superior to placebo in reducing behavioral symptoms of Tourette’s syndrome when used in combination with treatment drug haloperidol [64, 65].
Nicotine patches improved attention and behavior in a small study of children and adolescents with Tourette’s syndrome who were also on conventional therapy. Additional large-scale studies are needed to determine the effectiveness and safety of nicotine therapy in this population .
Extremely limited studies have linked cigarette smoking with a lower incidence of:
- Uterine fibroids 
- Canker sores 
- Endometriosis and endometriosis cancer  – nicotinic activators are being explored to treat endometriosis 
- High blood pressure
- Vomiting during pregnancy 
It’s important to remember that these studies looked at associations. They can’t tell us anything about the cause and effect. Smoking is responsible for many chronic diseases and smoking-disease-related deaths. The risks of smoking outweigh any potential benefit, though no health benefits have ever been determined.
Nicotine Replacement Therapy
How to Use
Stop smoking before starting nicotine replacement therapy. Your pharmacy will give you a Patient Information Leaflet that you should read before using nicotine inhalers.
In general, you should insert a cartridge into the mouthpiece and inhale for four 5-minute sessions or continually for about 20 minutes. You can remove the cartridge afterward and throw it away. Clean the mouthpiece with soap and water for the next use.
A minimum of 6 cartridges per day is usually recommended. Do not use more than 16 cartridges per day. The dose you use should be enough to reduce your cigarette cravings .
Contact your doctor or pharmacist if you have any questions about using nicotine replacement therapy.
Self-dosage typically ranges from 0.2-8.0 mg. A middle range is considered to be between 1-4 mg. Most gums and chews contain 2 mg per piece. Nicotine patches come in a selection of higher doses ranging from 5-21 mg, where the nicotine is released over a longer period of time.
Symptoms of Overdose
Nicotine poisoning is dangerous and delivers a biphasic effect – it first acts as a stimulant in the body but rapidly turns into a depressant. Vomiting is the most common symptom of nicotine poisoning and can begin as quickly as 15 minutes after ingestion .
Nicotine may also cause seizures and involuntary muscle twitching, as well as abnormal heart rhythms, a slow heart rate and fluctuating blood pressure .
In high concentrations, nicotine can cause heart failure, muscle paralysis and a buildup of fluid in the lungs’ air passages .
Call 911 if you or anyone you see has overdosed and is experiencing poisoning symptoms such as passing out or trouble breathing. Otherwise, call a poison control center right away.
US residents can call their local poison control center at 1-800-222-1222.
Canada residents can call a provincial poison control center.
Nicotine is lethal if ingested in high enough doses.
An oral dose of 50 to 60 mg of nicotine is enough to kill a 160 lb person .
Nicotine overdose can cause death in as little as an hour .
Nicotine overdose causes the same response in the body as toxic exposure to organophosphate insecticides and nerve agents such as DDT or Sarin gas .
Nicotine behaves the same way in the brain as acetylcholine. In excessive amounts, it will overload synapses and disrupt nerve impulses. Over-stimulation of neurons can cause the destruction of brain tissues .