Nicotine. You’ve probably heard a lot about this demonized substance, and unless you’re deep into the world of nootropics, it’s always in the context of smoking.
But is nicotine something you should be afraid of, or is it a powerful and underrated nootropic?
Let’s dive into the research.
What Is Nicotine?
Nicotine is an alkaloid; a class of naturally occurring organic compounds produced by plants, containing basic nitrogen atoms (1). Nicotine is found in abundance in tobacco leaves – although it can also be found in smaller doses in other members of the nightshade family, such as tomatoes or potatoes. Nicotine is known for its action as a Central Nervous System (CNS) stimulant, similar in many ways to drugs such as cocaine and amphetamines such as Adderall.
While this category also includes beloved daily-used Methylxanthines (aka caffeine in coffee, theobromine in chocolate and theophylline in tea), nicotine holds the title of the 2nd most abused substance after alcohol – the main representative of CNS depressants (2).
Nicotine, being a highly lipid-soluble molecule, can easily cross the blood-brain barrier, a membrane separating the CNS from systemic circulation (3), and find its way into the brain. This causes the characteristically satisfying effects of smoking such as euphoria, relaxation, and much more which we are going to analyze.
Fundamentals Of Neurophysiology
Our nervous system is divided into:
- The Central Nervous System (CNS)
- The peripheral Nervous System (PNS).
The PNS is further divided into the Somatic Nervous System (SoNS), and the Autonomic Nervous System (ANS).
The SoNS includes all the nerves that we can voluntarily control, such as those in our fingers, while the ANS includes everything else that is mandatory for bodily functions and survival but aren’t under our voluntary control, such as our heart rate, arterial pressure, and breathing.
SANS is responsible for the “Fight or Flight“ response – the neuronal and biochemical changes in our body needed to deal with a threat like an attack from a stranger on the street or a predator in the wild (4).
Immediately your heart beats faster, your pupils dilate, your breathing is noticeably more frequent and the majority of the vessels in your body constrict except the ones supplying blood to your muscles. In parallel, the bodily functions which are not useful in a fight or flight situation, slow down. These functions include digestion, urination, and sexual function.
This is why men have a difficult time getting an erection when they‘re stressed because the sympathetic nervous system takes over. On the other hand, the process of ejaculation is under the control of the SANS, so being extra nervous will likely mess with an erection but also lead to premature ejaculation.
To the contrary, the PANS promotes the “Rest and Digest” state. This includes increased salivation, gastrointestinal and sexual function, lower metabolism, and basically everything to maintain an energy-saving mode when the body doesn’t have to deal with stressful situations (5).
Nicotine’s Mechanism Of Action
After nicotine is consumed, it makes its way through the central nervous system and interacts with the brain’s nicotinic acetylcholine receptors (nAChRs).
Even though nicotine is not produced by our body, it is such a potent agonist of these receptors which neuroscientists named the receptors after. The nicotinic receptors are found in the autonomic ganglia, adrenal medulla, neuromuscular junctions, and of course, in our brain (6).
The nicotinic receptors are cholinergic receptors, meaning they respond to acetylcholine. Acetylcholine is one of the most important neurotransmitters, binding to muscarinic receptors, where nicotine has no affinity.
After nicotine binds to the nicotinic presynaptic receptors, it acts as an agonist and activates these receptors, leading to a significant release of many neurotransmitters including dopamine, gamma-aminobutyric acid (GABA), and even catecholamines from the adrenal medulla like adrenalin. This causes systemic effects in the body and mind.
The release of these neurotransmitters, and primarily of dopamine in brain areas like the Nucleus Accumbens, results in the rewarding and pleasurable effects of nicotine. Whereas this strong neural signal in other primary brain areas plays a significant role in cognitive function and alertness.
There is something interesting about nicotine – in low to medium doses it is a stimulant, but in higher doses, this is reversed and nicotine has a depressive-sedative effect. This phenomenon is known as “Nesbitt’s paradox”, (7) having gotten its name from the doctor who first described it. In doses over 60 mg nicotine dampens neuronal activity leading to respiratory paralysis and eventually death (8).
Uses
Nicotine’s clinical use so far is limited to helping patients quit smoking. A dermal patch or gum is typically used with a low dose of around 4mg of nicotine. This is approximately 2-3x the amount of nicotine contained in one cigarette. This method increases the chances of successfully quitting smoking by 50–60% (9). In the last year, the use of an inhaler has been preferred by an increasing amount of smokers who aim to quit. However, this method carries a few risks – some caused by the rapid absorption of nicotine through millions of lung alveoli (10).
Besides that, another application of nicotine is as a pesticide (11, 12). This is based on the toxic effect of nicotine on small animals, fungi, and pests. According to this research, the applications of nicotine in our everyday life seem to be restricted.
Nicotine As A Nootropic
Keep in mind that so many people choose to smoke as a lifestyle, even though data strongly supports its destructive effects on almost every part and organ of our body.
But even though nicotine consumed through smoking has many bad effects, nicotine itself also has positive ones (especially for the brain).
It has numerous positive effects on the smoker (at least temporarily); nicotine feels good, it relaxes you, it increases your focus, and may help you think better.
But is nicotine powerful enough to be considered a nootropic?
Nicotine Improves Short And Long-Term Memory
One of the most interesting findings is nicotine’s effect on memory. Numerous studies have indicated that taking nicotine can help you memorize things better and even enhance your long-term memory.
Human studies have shown that nicotine strongly affects attention, fine motor skills, working memory, and episodic memory.
Nicotine affects ‘spike-timing-dependent-potentiation’, which is a process that drives changes in the integrity of neuron cell connections. Studies have also shown that nicotine excites various ‘interneurons’ inside the prefrontal cortex – interneurons being where neuronal signals travel through (13).
Naturally, because nicotine has been shown to improve memory and overall cognition, it has been studied in individuals who are experiencing neurodegeneration. Alzheimer’s disease is a great example. Amyloid plaques are the primary driver of neuron death in Alzheimer’s disease. These plaques drive the gradual deficit in one’s cognitive performance with time.
Multiple studies show that nicotine can improve memory, attention, and general cognition in people suffering from Alzheimer’s disease. Some studies suggest that nicotine inhibits the development of amyloid plaque formation, but the research is still in its early stages on this specific matter (14), (15).
This sounds amazing and it is. But the question remains, can nicotine be used as a first-line treatment for these patients who don’t really have anything else to help them?
We simply don’t know.
In saying that, the current findings in studies that have been carried out do show potential to alleviate age-related cognitive disease, which is exciting!
Nicotine Improves Concentration And Cognition
Nicotine can markedly boost your concentration and cognitive skills (16). You’ve probably noticed smokers light a cigarette when they need to deal with a mentally demanding problem, and data supports this.
Nicotine has been shown to increase concentration and working memory. These changes occur because nicotine activates nicotinic acetylcholine receptors in the brain – primarily in the prefrontal cortex. The prefrontal cortex is an area of the brain responsible for higher thinking and executive function.
Two areas of the brain which relate to the cognitive effects of nicotine include:
- Prefrontal cortex
- Hippocampus
So why does nicotine improve these areas of the brain?
This may be due to nicotine improving signal-to-noise ratios, or facilitating synaptic plasticity, in specific neural circuits (17).
Topographic imaging studies have helped researchers to identify regions of the brain which nicotine activates.
These studies are conducted by using magnetic resonance imaging (fMRI).
In one study, researchers provided two groups of participants a task that requires a high level of attention to successfully complete. One group were smokers, and the other group was non-smokers. Results from fMRIV scans showed that smokers had a significantly higher activity level in areas of the brain required to focus on the task which they were completing (18).
Nicotine Improves Attention
Several studies have indicated that nicotine can improve attention in patients suffering from ADHD. ADHD, formally known as Attention Deficit Hyperactivity Disorder, is a mental disorder typically diagnosed at a young age and characterized by difficulty in paying attention (19). Even though the medical treatment of ADHD is based on other stimulatory drugs like Methylphenidate (Ritalin) and Amphetamines (Adderall), studies have shown that nicotine can increase the attention of these patients and furthermore improve other ADHD symptoms like anxiety and mood disorders (20).
Interestingly, in a double-blind study, nicotine was shown to improve attention in healthy adults. Specifically, nicotine was shown to decrease the number of omission errors during testing, and decrease the variance in “hit reaction time” which is used as a measure of attentiveness (21) (22).
Nicotine Can Enhance Your Intelligence 
Okay. This sounds far-fetched, but nicotine could very well increase intelligence, at least in the short term. Despite the fact that I’m skeptical about this one, there are a couple of studies claiming that nicotine can increase your overall intelligence.
For example, in some research, volunteers who were allowed to smoke before completing an IQ test scored higher than the group which didn’t have this privilege.
Of course, we can’t exclude the likelihood that this result may have been due to the impaired concentration of smokers who weren’t allowed to smoke, resulting in them having mild withdrawal symptoms. Nevertheless, the above-mentioned findings demonstrated that nicotine increases the efficiency of neural communication between specific brain areas involved in cognition (23).
Nicotine Reduces Stress And Anxiety While Increasing Alertness
This sounds too good to be true but studies show it clearly. Nicotine increases alertness and can also promote feelings of calmness. Of course, how nicotine affects one’s state of mind is subjective to their own neurobiology. For example, a person who is already anxious may experience beneficial calming effects from nicotine, while someone who is too calm may become increasingly alert and anxious (24). Interestingly, the mood-stabilizing effect of nicotine is more potent in females, where it has been shown that it may provoke males. This proposes a sex–dependant way of action, (25) which partly explains the augmented nicotine addiction that has been observed in women (26).
This brings us to the real question: can we take advantage of nicotine’s wholesome effects or is it better to stay away from it?
Side Effects of Nicotine
Serious Addiction: Despite what many websites may claim, blaming the addiction to smoking, nicotine by itself is extremely addictive. Actually, it is as addictive as heroin – that being its biggest disadvantage. Dopamine, glutamate, and GABA all play an important role in nicotine addiction.
In parallel, tolerance develops – aka the downregulation of nicotinic receptors. This results in a decreased amount of dopamine release and therefore reward, as well as an intense urge for the individual to bring their dopamine levels back to normal by taking more nicotine.
Interestingly, research has shown that nicotine dependence is highly contingent on genetics. Research has shown that subtypes of nicotinic receptors, and other genes involved in cognitive function, play an important role in one’s inclination to be addicted to nicotine. This means that someone may not get addicted but another person will.
Nicotine may have some side effects such as:
- Dizziness
- Stomach discomfort
- Throat or mouth soreness
- Watery eyes or dry mouth
- Headaches
- Bowel disturbances
Nicotine can also lead to anorexia, changes in taste, and allergic reactions (27), (28).
Contraindications
Pay attention to NOT use Nicotine in the following situations:
- Women during pregnancy OR lactation – Nicotine is highly lipid-soluble making it very easy to pass through the placenta and be transferred to the embryo causing birth defects. Nicotine’s teratogenic effect is a major reason why smoking during pregnancy is forbidden.
- People with Peptic Ulcer disease – Nicotine may delay the healing of peptic ulcers.
- Cancer patients – Even though it is clear that nicotine does not cause cancer, there is some data supporting that it can worsen cancer. Nicotine promotes neoangiogenesis, a process essential for tumor growth, so it is not the best idea to promote nicotine use.
- People suffering from hypertension – Nicotine acts on the adrenal medulla and increases the release of catecholamines, which in turn increases vascular tension and the heart rate.
- People who are diabetic – Nicotine can acutely reduce insulin sensitivity.
- People who are allergic to nicotine.
How To Take It
If you decide to use nicotine, it is essential to start with low doses, and ideally try to maintain these doses at around 1 mg. Most nicotine gum products come in 4 mg doses, but this is too high a dose, especially for a newbie. Dermal patches contain a far higher dosage, but they can easily be cut to the right dosage, making it a great choice. We wouldn’t recommend you use a vapor as its side effects aren’t sufficiently understood yet.
It needs to be clear that nicotine should not be used as an everyday nootropic. You should restrict its use to especially demanding occasions, like an important test or meeting, using it no more than once a week.
Exceeding this can result in addiction or tolerance, meaning that normal doses will not do their job anymore, and the brain will demand higher and higher dosages. This is due to the downregulation of nicotinic receptors in the brain.
Dosage adjustments are needed in case of severe renal or hepatic impairment.
At any cost, do NOT take your nicotine by smoking.
Aside from all the well-known negative effects, studies have shown the reduced thickness of the medial orbitofrontal cortex, a structural modulator of cerebral function and cognition, in smokers (29).
This means that in the long term, smoking will lead to cognitive impairment.
Summary
Nicotine promotes the release of various neurotransmitters. This can have beneficial effects, like improving memory, concentration ability, relaxing you, or increasing your alertness, and even making you think faster.
Is nicotine a powerful nootropic? Definitely. Should you use it?
We would suggest not to, unless you really have to and, in that case, always in low doses, not more than a couple of times per week and never ever by smoking.
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