When most people think of nicotine, they think of smoking cigarettes or other tobacco products. Since tobacco products are linked to various types of cancer (e.g. lung cancer from smoking), many people assume that nicotine is inherently evil. While nicotine is considered one of the most addictive drugs, there isn’t significant evidence supporting the idea that it causes cancer.
While cancer is commonly associated with nicotine due to the fact that nicotine is in cigarettes, this is mostly due to tobacco as well as the upwards of 7,000 chemicals added to these products. When used in the form of a standalone patch, a person is capable of attaining a psychological “buzz” or cognitive enhancement from nicotine, without the dangerous toxins associated with smoking cigarettes.
For this reason, many people resort to smoking cigarettes or even just using nicotine patches as a way to remain calm and focused during cognitively demanding tasks. Nicotine is considered a nootropic and can be used as a “smart drug” to maximize cognitive capacity, plus some evidence suggests that it may act as a neuroprotective agent. Examples of tasks that people have found benefit from using nicotine include: solving complex mathematical equations, taking exams, and technical writing.
What is nicotine? + How it works.
Nicotine is considered a parasympathetic alkaloid derived from nightshade plants (Solanaceae). It acts as a stimulant drug, speeding up activity in the central nervous system and brain, giving people increased physical and mental energy. It functions by stimulating the nAChR or “nicotinic acetylcholine receptors” as an agonist, meaning it binds to that receptor and elicits a physiological response associated with that receptor.
There are a couple of exceptions to its nicotinic acetylcholine receptor agonism, specifically at the Alpha-9 and Alpha-10 nAChR receptors, where it functions as an antagonist. As a result of agonism at the nAChR receptors, nicotine increases stimulatory neurotransmitters including dopamine. When inhaled as smoke, a monoamine oxidase inhibition effect can be observed as a result of harman and norharman.
Therefore levels of dopamine, norepinephrine, and serotonin all increase as a result of nicotine usage. Furthermore, nicotine stimulates the sympathetic nervous system, leading to a release of epinephrine (adrenaline).Upon inhalation of nicotine, it passes through the blood-brain barrier within 20 seconds. Due to the stimulatory effects and favorable alterations in neurotransmission as a result of nicotine ingestion, many people use it as their drug of choice.
Unfortunately, this lucrative boost in neurotransmitters like dopamine is likely also responsible for its addictive properties.
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC526783/
- Source: http://www.ncbi.nlm.nih.gov/books/NBK53018/
Hidden Benefits of Nicotine on the Brain
Although nicotine in tobacco is responsible for the cancer, illness, and mortality of millions of people, when used in its pure form, it may hold significant therapeutic value. These benefits have been documented since the early 1990s and research continues to unveil new therapeutic potential.
ADHD: There is evidence dating back to the 1990s suggesting that nicotine may be useful for treating various symptoms of ADHD (attention-deficit hyperactivity disorder). A placebo-controlled, double blind experiment was conducted in 1996 with 17 adults (6 smokers and 1l nonsmokers) all of whom either had referrals for ADHD or were diagnosed by standard DSM-IV criteria. The 11 smokers ceased from smoking for one night and were given 21 mg per day of a transdermal nicotine patch for 4.5 hours in the morning.
The nonsmokers were administered 7 mg per day of a transdermal nicotine patch for 4.5 hours in the morning. Researchers administered either an “active” patch containing nicotine or a “placebo” patch containing nothing. It was documented that nicotine significantly improved measures on the Clinical Global Impressions (CGI) scale due to the fact that nicotine increased vigor (as recorded by a Profile of Mood States (POMS) test.
Furthermore, nicotine reduced reaction time on a Continuous Performance Test (CPT), and significantly reduced a measure of inattention. Researchers from this study concluded that nicotine deserves further therapeutic investigation for its potential to treat symptoms of ADHD. Research from 2001 compared nicotine’s effect with that of a placebo and methylphenidate (Ritalin) in treating attentional deficits.
A small study of 40 participants demonstrated that administration of nicotine improved performance on an objective computerized attention task and reduced ADHD. A case report documented in 2008 highlighted the fact that an adult diagnosed with ADHD with comorbid anxiety and depression, responded well to transdermal nicotine patches. While the researchers discuss a potential placebo effect, they also speculate that nicotine agonists may be effective new treatments for ADHD.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8741955
- Source: http://www.ncbi.nlm.nih.gov/pubmed/11519638
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2446482/
Antidepressant: Nicotine has been well-documented as eliciting antidepressant effects in both humans and animals. Nicotine’s mechanism of action on nicotinic acetylcholine receptors is believed to affect neural pathways involved in a person’s mood, resulting in changes after ingestion. In part, nicotine’s effect on the nAChR receptors may help reduce stress, while simultaneously improving mood.
- Brain waves
- Monoamine oxidase inhibition
- Regional activation (Symmetry)
There are a number of ways by which nicotine may facilitate an antidepressant response in humans. A myriad of nicotine-induced changes such as: altered brain waves, neurotransmitter levels and receptor density changes, different regions becoming active in the brain, as well as increased CNS stimulation – may contribute to the antidepressant effect. Those with depression are often “understimulated” and nicotine exposure may increase their stimulation.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22743591
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15610943
- Source: http://www.ncbi.nlm.nih.gov/pubmed/9746444
Anxiolytic: It is known that nicotine also can decrease levels of anxiety in humans and animals. The way nicotine reduces anxiety is thought to be a result of its ability to modify neural pathways that are heavily responsive to stress and anxiety. That said, the anxiolytic properties of nicotine are difficult to pinpoint, and may be chalked up to a variety of factors.
Nicotine is known to increase alpha waves, or brain waves associated with relaxation – which may help combat feelings of anxiety. Additionally, it has subtle effects as a monoamine oxidase inhibitor, leading to decreased breakdown of “feel good” and relaxation-inducing neurotransmitters like dopamine, serotonin, and norepinephrine.
It is important to note that not everyone experiences an anxiolytic effect from nicotine, in fact the substance may provoke anxiety in a certain subset of the population. For most people though, nicotine acts within the lateral septum, dorsal raphe nuclei, mesolimbic dopamine system, and hippocampus to decrease anxiety.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12151749
Brain waves: Oddly enough, nicotine is capable of significantly changing the electrical activity within your brain. Most people during a waking state have predominantly beta brain waves – these are associated with stress and alertness. However, one study hooked EEGs (electroencephalographs) up to tobacco smokers and determined how their brain waves were affected.
It seemed as though tobacco smoking produced significant increases in alpha waves. These increases were noted as being “bilateral” or occurring across both hemispheres of the brain. While it may seem counterintuitive that nicotine may increase alpha waves due to its stimulatory effects, the stimulation is primarily upon the brainstem reticular activating system.
This means that nicotine can put people in a state of creative alertness as alpha waves are associated with creativity. Among those with depression, it is thought that asymmetry in frontal and posterior cortical regions are responsible for the low mood. Transdermal nicotine administration was found to increase bilateral alpha waves rather than solely affecting one hemisphere of the brain.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19765621
Cognitive enhancement: Nicotine has been well-documented for its ability to enhance cognitive function and overall performance. Research published in 2001 highlighted the fact that transdermal nicotine administration in the form of “patches” treated a certain cognitive impairments associated with Alzheimer’s disease, schizophrenia, as well as attention-deficit hyperactivity disorder (ADHD). Studies conducted on animal models have shown that nicotine significantly boosts working memory with chronic exposure.
- Episodic memory
- Long-term memory
- Processing speed
- Social cognition
- Working memory
It is believed that nicotine’s ability to enhance cognition may partially result from its stimulation of both the Alpha-4-Beta-2 (A4B2) and Alpha-7 nicotinic receptors. The A4B2 receptor is specifically involved in learning, while the Alpha-7 receptor is primarily involved in long-term memory processes. Researchers have long speculated that novel nicotinic agents should enhance cognitive function in healthy individuals and improve performance among those with impairment.
The NIDA (National Institute on Drug Abuse) was the first to demonstrate that nicotine enhances activation of the parietal cortex, which directly contributes to improvements in attention. They discovered this by comparing brain activity during a “sustained attention task” (rapid-visual information processing) with a lesser demanding “sensorimotor control task.” Researchers discovered that nicotine significantly boosted activation in the occipital cortex during both tasks.
Furthermore, nicotine also increased activity in the parietal cortex during the “sustained attention task,” leading to enhanced performance. Studies dating back to the 1990s demonstrate that nicotine improves attention in a variety of tasks, improves working and long-term memory, and attentional capacity.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/11230877
- Source: http://www.ncbi.nlm.nih.gov/pubmed/1579636
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23474015
Neurodegenerative diseases: There is mounting evidence to suggest that nicotine may not only prevent development of various neurodegenerative diseases (e.g. dementia), but it may help treat symptoms among those that are already suffering from neurodegeneration. A study published in the year 2000 suggested that nicotinic receptors should be studied for their influence on CNS functions, specifically related to Alzheimer’s and Parkinson’s disease.
- Alzheimer’s: Some studies have suggested that smokers tend to experience Alzheimer’s disease at reduced rates compared to non-smokers. There is some controversy associated with these studies, but it could be that stimulation of the nAChR may prevent age-related decline associated with Alzheimer’s.
- Parkinson’s: There is some evidence to support the idea that nicotine may improve both cognitive performance and motor abilities among individuals with Parkinson’s. Additionally, it is thought that nicotine is capable of increasing processing speed for complex tasks.
As an example, these researchers highlighted nicotinic agonists like ABT-418 due to the fact that it improves both verbal acquisition and retention, while simultaneously decreases information errors. Researchers speculate that nicotinic agonists will be used as an adjunct treatment for those with neurodegenerative diseases.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/10812945
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12446934
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17147565
- Source: http://www.ncbi.nlm.nih.gov/pubmed/9303280
Neuroprotective agent: Evidence has been suggesting since the 1990s that nicotine may protect the brain from neurodegenerative diseases like Parkinson’s and Alzheimer’s. Whether it actually is capable of preventing neurodegeneration is subject to significant debate. Even if it doesn’t fully protect against neurodegenerative diseases, it likely has neuroprotective properties.
A few theories emerged in 1996 pertaining to the mechanisms by which nicotine may prevent neurodegeneration. These mechanisms included: reducing estrogen levels, altering production of prostaglandin, and stimulation of nicotinic acetylcholine receptors in the CNS. The theory that most believe is responsible is that of nAChR (nicotinic acetylcholine receptor) stimulation.
In 1997, it was reported that among individuals with neurodegenerative diseases, there appears to be a significant reductions in the total volume of nicotinic acetylcholine receptors. Since smoking is the most popular modality of nicotine ingestion, and smokers tend to have decreased incidences of Parkinson’s disease, it should be speculated that nicotine may be neuroprotective, or at least neuroprotective for certain individuals.
A report from 2012 suggests that nicotine administration in animals protects their brain from damage in the nigrostriatal area, a dopaminergic pathway that connects the striatum with the substantia nigra. Another mechanism by which nicotine may protect the brain is by activating intracellular transduction pathways by altering calcium signaling.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8746297
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22693036
Neurotransmitter increases: Nicotine is known to affect a variety of neurotransmitters including: dopamine, serotonin, norepinephrine, and epinephrine. Being a nicotinic acetylcholine receptor agonist, nicotine mimics the effects of acetylcholine in the brain. The alterations made to the brain by nicotine ingestion makes it an appealing drug for many individuals, including those with: ADHD, anxiety, depression, and schizophrenia.
Nicotine is known to possess dopaminergic properties, increasing dopmaine levels in the brain, which lead to improved cognitive function. It is also known to increase serotonin levels via its ability to act as a monoamine oxidase inhibitor. Monoamine oxidase inhibition essentially prevents the enzymatic breakdown of neurotransmitters like dopamine, serotonin, and norepinephrine – leading to increases in their endogenous levels.
Although it is unknown as to whether long-term nicotine usage is associated with diminishing returns or a “tolerance” to the effects of the neurotransmitter changes, short-term and moderate-term usage clearly elevate their levels. This may lead to mood improvements, superior cognition, and better overall functionality.
Performance enhancement: Many people use nicotine as a performance enhancing drug, whether it be cognitively, physically, or a combination of both. While caffeine remains the most widely-used performance enhancing agent, nicotine is thought to be the second. Professional athletes may use nicotine as a way to increase level of arousal so that it’s within an optimal range, without going overboard; according to the Yerkes-Dodson Law, too much stimulation compromises performance.
- Alerting attention
- Fine motor skills
- Orienting attention
- Response accuracy
- Response time
One meta-analysis analyzed all placebo-controlled, double-blind studies from 1994 to 2008 regarding nicotine and performance. A total of 41 studies fit the necessary criteria as determined by researchers in that they were double-blind, placebo-controlled, and analyzed nicotine’s effect on human performance. They noted enhanced performance in domains of: memory (working and episodic), alerting attention (accuracy, response, and orienting), and motor abilities.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/20414766
Relaxation: Many smokers claim that having a cigarette “relaxes” them. To those that are aware of the stimulatory properties of nicotine, this may sound like nonsense. However, nicotine appears to provide calming effects in a number of ways, including via modification of neurotransmitter levels, particularly dopamine and serotonin.
Additionally it has also been shown that smoking cigarettes increases bilateral alpha waves – brain waves associated with relaxation. That said, research from the 1980s suggests that part of the relaxation-induction as a result of nicotine ingestion is due to the fact that a symptom of nicotine discontinuation is anxiety. By continuing to smoke, the anxiety is lessened and smokers claim to feel more relaxed.
In studies conducted on rats, it was found that nicotine enhances smooth muscle relaxation. This increase may be similar among humans, although it hasn’t been tested.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/7086634
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25832423
Schizophrenia: Those with schizophrenia often have severe cognitive deficits or impairment. It is widely established that many individuals with schizophrenia self-medicate with nicotine. One reason for such self-medication is that nicotine may help ameliorate the cognitive symptoms of schizophrenia, improving a person’s ability to learn, remember, and function.
Specifically, nicotine is thought to help individuals with schizophrenia by its action on Alpha-4-Beta-2 nicotinic acetylcholine receptors. Rodent studies have shown that agonists of Alpha-4-Beta-2 nACh receptors (i.e. nicotine) improves cognitive impairments in domains of processing speed, visual learning, working memory, and social cognition. Several preliminary human studies have shown benefit from compounds that target the Alpha-4-Beta-2 nACh receptors.
In other words, nicotine helps improve certain symptoms among those with schizophrenia, particularly those related to cognition. Schizophrenia is thought to be a disorder of the dopamine system, leading to chaotic dopaminergic activity. Nicotine is believed to help stabilize or normalize dopaminergic activity, improving overall functionality among those with schizophrenia.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/20109141
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15265251
Tourette’s syndrome: Nicotine may offer some benefits for those with Tourette’s syndrome. Trials documenting the administration of transdermal nicotine as well as nicotine gum were found to enhance the efficacy of neuroleptic drugs in reducing dyskinesia-based symptoms of Tourette’s syndrome. A study conducted over a period of 33 days discovered that transdermal nicotine was superior to a placebo in reducing behavioral symptoms of Tourette’s syndrome when used as an adjunct to the neuroleptic haloperidol.
This effect of reducing behavioral symptoms continued even after the patch had been discontinued for 14 days, and even when the dose of haloperidol was cut in half. A separate review of evidence found that administration of 2 mg nicotine gum or 7 mg nicotine patches enhances the therapeutic properties of neuroleptic drugs. Most findings highlight the beneficial effects of nicotine as an adjunct treatment for those with Tourette’s.
Acute transdermal nicotine administration tends to improve attentional processes and behavioral symptoms in children and adolescents with Tourette’s syndrome. It was also found to reduce complex tics according to self-reports from the patients.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/11681767
- Source: http://www.ncbi.nlm.nih.gov/pubmed/9336013
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15132126
What is the safest source of nicotine?
With nearly any source of nicotine, you run the risk of becoming addicted. Some people (and experts) believe that taking low doses of a transdermal patch, gum, or lozenge may bypass any potential for addiction. Those that inhale the nicotine such as via smoking, an inhaler, or nasal spray may be at a greater risk for addiction. When inhaled, there’s less of a time gap between ingesting nicotine and it passing through the blood-brain barrier.
- Safer: Transdermal patch – It provides consistent delivery at whatever dose you purchase.
- Safe: Gum / Lozenges – Don’t provide as consistent of delivery as the patch, but don’t provide as rapid of delivery as an inhaler.
- Questionable: Inhaler / Nasal Spray – Inhaling nicotine dramatically increases potential for addiction.
- Risky: Tobacco products – These contain carcinogens and are engineered to be as addictive as possible.
Any form of pure nicotine should be considered safer than that found in tobacco products due to the fact that there are thousands of other chemicals within the tobacco products that cause cancer. Additionally, activities like smoking pack a powerful punch by delivering nicotine to the bloodstream within just seconds. Tobacco products also elicit a greater effect of monoamine oxidase inhibition (MAOI) than other modalities of nicotine delivery.
Some individuals that use only transdermal nicotine patches and have never smoked argue that they are less addictive due to the fact that there is no associated ritual and the nicotine isn’t as quickly absorbed as it is via smoking. Proponents of the patch suggest that when taken at low or microdoses, it provides a performance improvement without the risk of addiction or cancer.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8614162
Considering short-term vs. long-term nicotine usage…
It is known that the more frequently you use nicotine, the greater likelihood you will be to continue using nicotine. This is due to the fact that each successive nicotine ingestion strengthens reward centers in the brain that elicit pleasurable effects. Over time, the brain comes to expect nicotine and behaviors related to the ingestion of nicotine become difficult to avoid.
Using pure nicotine over a short-term is known to enhance cognitive function and performance. Over the long-term, it may even protect the brain from various forms of neurodegeneration via its mechanism on nicotinic acetylcholine receptors (nAChRs). That said, many nicotine users have noticed that over the long-term, the effect of nicotine diminishes, requiring greater amounts of nicotine to achieve the same effect.
In fact, some have suggested that over the long-term, the brain may become reliant on the nicotine to perform, leading to potential deficits when a person is without it. Those that use nicotine and/or products containing nicotine should carefully assess whether the short-term benefits outweigh the potential long-term consequences. The consequences may be especially detrimental for those who begin smoking in adolescence.
Since the brain is not fully developed until about age 25, cigarette smoking and/or nicotine ingestion could impair development of the prefrontal cortex region of the brain. The prefrontal cortex is a region responsible for advanced thinking, problem solving, and organization of thoughts. It is considered the region that gives us control over our older, “reptilian” or instinctual brain.
Unfortunately smoking during adolescence actually increases risk of cognitive impairment later in life. It also significantly increases risk for developing a psychiatric illness such as major depression or anxiety. Years of smoking has also been suggested to cause attentional deficits and is known to create significant molecular changes to the adolescent brain.
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3543069/
- Source: http://www.ncbi.nlm.nih.gov/pubmed/10985354
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12151749
Optimal dosage of nicotine for therapeutic benefit?
There’s no “optimal” dosage of nicotine for each person. For those that take it (or are going to take it), it is recommended to always start with the minimal effective dose. In some cases, a person may not feel a noticeable “buzz” when ingesting nicotine at low doses, and that may be a good thing. The buzz is part of the reason that smoking cigarettes have become so addictive – it changes a person’s brain waves and concentrations of neurochemicals like dopamine.
Whenever considering dosing, it is also important to take into consideration the modality of delivery. Someone that’s smoking the nicotine is more likely to get addicted because the cigarette packs a potent punch of instant delivery through the blood-brain barrier. A patch on the other hand provides a more consistent delivery over an extended period of time.
Most “patches” have equivalencies to number of cigarettes smoked such as 1 patch may provide the same amount of nicotine as 10 cigarettes. To avoid addiction, it should be recommended to pursue the patch with the least total amount of nicotine. This has lead some people to consider cutting the patches, however one should proceed with caution when using this method as to avoid potential leakage.
Weighing the pros and cons of using nicotine…
Those that use any drug, including nicotine should weight the potential benefits with the drawbacks. Nicotine shouldn’t be thought of as a “wonder drug,” yet it also shouldn’t be dismissed as having no potential therapeutic value. Clearly there are problems associated with ingestion of tobacco products, specifically cancer.
In addition to the potential of getting cancer, a person must take into consideration the purchases of those tobacco products. Due to the addictive nature of tobacco products, the associated costs can quickly put a dent in the finances of an individual that is addicted. These costs accumulate over time, leading the average person to spend over $5,000 per year on just cigarettes; add this up over 10 years and that’s $50,000 gone.
While pure forms of nicotine such as transdermal patches may be safer in that they do not contain chemical additives and impurities, they may also become addictive. Although the cognitive enhancement may be beneficial, it is thought that even this effect will gradually subside over a long-term, particularly with chronic nicotine exposure. Furthermore, many people experience unwanted side effects and severe nicotine withdrawal symptoms upon discontinuation.
Does this article suggest that you should start using nicotine?
No, this article was written with the intent of educating people regarding the potential therapeutic value of nicotine. In no way is it meant to encourage or promote the usage of nicotine as a “wonder drug” or a substance that everyone should use. As with any drug or substance, it is important to realize that there’s no biological free lunch, meaning whatever “benefits” you experience from the drug, you’ll also likely experience equally oppositional “drawbacks.”
A majority of neuroscientists and physicians discourage the usage of nicotine, even in the pure form. The usage is discouraged in part because there are no large scale studies analyzing the potential risks and benefits, and there also is still a potential for addiction. If you’d like more information about nicotine, you may want to chat with a physician or even a neuroscientist.
Have you used pure nicotine as a cognitive enhancer or alternative treatment?
It is evident that smoking tobacco and using tobacco products is damaging to a person’s health and should be discouraged. However, there is clear therapeutic potential associated with nicotine that should be considered for future drug development. Perhaps the most interesting avenue of exploration in regards to nicotine is for the treatment of neurodegenerative diseases.
If you have used pure nicotine as a cognitive enhancer or as an alternative treatment, feel free to share your experience in the comments section below. Discuss the type of nicotine that you used, the degree to which it has helped improve your performance or treated a particular condition, as well as the dosage you used. Also mention whether you think you’re addicted to its effect, whether you’ve experienced any side effects, or had a difficult time trying to discontinue it.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/1859921
- Source: http://www.ncbi.nlm.nih.gov/pubmed/9006184