Thread by @NoahRyanCo

The conclusive guide to Nicotine

Used correctly, this plant compound can give you better memory, focus, and attenuate learning

Used improperly, It can cause ED & Hair loss

What it is, how to use it, and how its different than tobacco:

Before diving into the pharmacology of nicotine we first need to make distinctions

Nicotine ≠ Tobacco

Nicotine is a psychoactive alkaloid found in most nightshades. Tomatoes, eggplants, potatoes, bell peppers etc.

Although it's most abundant in tobacco (also a nightshade)

Like caffeine, nicotine is a natural pesticide. It’s technically a neurotoxin.

The same properties that make it toxic to small pests make it stimulating & addictive to humans.

Tobacco has been used as a medicine & stimulant for the last 2,000 years. It was first isolated in 1828 by a German doctor & chemist & has been demonized ever sense.

But nicotine’s benefits are too pervasive to ignore.

All discussions & distinctions regarding nicotine & tobacco must be made in isolation.

I’ve always been drawn to nicotine.

Not from an addiction standpoint but from a “hey maybe this demonized molecule isn’t as bad for you as they say it is” standpoint

Most great historical thinkers were nicotine fiends

Philosophers with their pipes, Generals with their cigars. Anybody who used their brain used nicotine. Its historical significance rivals caffeine.

The unsung hero of cultural & societal development

There’s a reason nicotine’s so popular. It makes you smarter, sharper, focused, & alert.

It alleviates pain & treats depression (just google any of these + nicotine & you’ll find plenty of studies)

Neurologically speaking, nicotine improves:

• Learning & memory
• Information processing
• Cognitive flexibility (task switching)
• Mood
• Neuroprotection
• Fine motor skills
• IQ

It’s both a stimulant and a nootropic. It stimulates the adrenal glands to release adrenaline, but also improves cognitive performance.

So no, nicotine's not just a meme. It's efficacious.

It’s special in that it’s the fastest acting cognitive enhancer out there. It passes the blood brain barrier (BBB) almost immediately.

It reaches peak brain concentration within 10-20 seconds & has a half-life of only 2 hours.

But there’s a catch

Like most substances, nicotine's benefits happen in a window. Too much nicotine & you’ll notice negative effects.

Most of nicotine’s benefits come from one unique mechanism: Nicotine lights up your nicotinic acetylcholine receptors (nAChRs)

It binds to these receptors like acetylcholine but stays around significantly longer.

The cholinergic system is essential for memory, learning, and focus. The dopaminergic system is great for motivation, but if you want to improve cognition don’t neglect the cholinergic system

Most of these nACh receptors are located pre-synaptically.

Their activation modulates the release of other neurotransmitters like dopamine, serotonin, glutamine, GABA, and norepinephrine.

This is what makes nicotine paradoxical.

It’s wide array of neurotransmitter activity. It can calm you down when you’re anxious & give you energy when you’re fatigued.

This is also why it has different effects on different people (all depending on their existing neurochemistry)

Typically when receptors are exposed to excess amounts of activity, they downregulate

It seems as if nicotine exposure actually UPregulates nAChRs through “Enhanced Intracellular Maturation”.

Nicotine by this theory actually results in more nACh receptors on the cell surface.

This is one of the reasons you get withdrawals: It acclimates to elevated nAChR activity & establishes that as the new “normal”.

Increased cholinergic receptor sensitivity has also been linked with depression, so something to consider (cholinergic hypothesis of depression)

Like all neurotransmitters, having too much or too little is equally undesirable. I believe that most people today have choline deficiencies, especially those with ADHD-like symptoms

Choline is the dietary vitamin that creates acetylcholine neurotransmitters. If you notice a major boost from nicotine, you might be choline deficient.

Test this theory out by supplementing with a choline source (egg yolks or CDP-Choline)

NICOTINE VS TOBACCO

Nicotine is to tobacco as caffeine is to coffee. It a single psychoactive alkaloid that is part of a larger compound. You cannot conflate the two.

Tobacco has its own unique benefits & downsides (with medicinal & spiritual significance)

A lot of the esoteric benefits of nicotine (anti-parasitic, anti-v1ral, pro-DHT) come from the tobacco plant itself, not nicotine in isolation.

First of all, smoking anything will put your body in an inflammatory state.

It releases reactive oxidative species that rob you of vitamin C & E, as well as deplete collagen.

An exceptionally toxic form of mold called aflatoxin B-1 grows rampantly when tobacco is cured. This is also why chewing tobacco is linked with face cancer

If you’re looking to minimize side effects & get full cognitive benefits, opt for isolated nicotine over tobacco.

Smoking cigs, even organic, will cause more damage to your skin, lungs, mouth & overall inflammatory state significantly more than nicotine alone.

It’s also nearly impossible to get the minuscule doses desirable for cognitive enhancement.

Cigarettes have higher addiction potential because of the habitual & ritualistic nature of ripping a heater. The roll, the light, the draw, the inhale, the hand-to-mouth synergy.

The action is addictive of itself, further reinforced by nicotine.

If addiction is a concern, patches are the least habit-forming. They’re also the most accurate when it comes to dosing.

NICOTINE & DOPAMINE

Nicotine releases dopamine in the nucleus accumbens (part of brain’s reward system) AND the pre-frontal cortex (executive function headquarters). This is what makes it not only pleasurable in & of itself but also reinforces accomplishment-driven behavior.

NICOTINE & BRAIN NETWORKS

Nicotine has profound effects not encompassed by its cholinergic properties: modulating the Default Mode Network & enhancing alpha brain waves

Your default mode network is essentially the part of your brain responsible for daydreaming, rumination, mental wandering, & worry

It’s what enables you to think about the past & the future. It’s what gives you theory of mind & the experiential self.

The default mode network is what gives you sense of self. It’s also a cause of a lot of unnecessary worry: what happened, whats going to happen, what other people think about you.

This network is great. It’s what makes humans such complex thinkers.

BUT when it goes unchecked you get caught up in these ruminating thoughts & worries.

Nicotine dampens this network & enhances the salience network

It’s by this mechanism that nicotine quells overthinking. It can help you get out of your head on focus on the task at hand.

It also increases alpha waves. Think of this as the “meditating monk” wavelength. A mental state where you are both relaxed & alert of your surroundings.

This is the exact goal of meditation & psychedelics: to disrupt the DFM & increase alpha brain waves.

ADRENALINE RELEASE:

Nicotine releases a hormone (CRH) which releases another hormone (ACTH) which releases adrenaline from the adrenal glands. Hence the fight-or-flight response of nicotine:

• Heightened senses
• Release of energy stores
• Elevated blood pressure

NICOTINE IS NEUROPROTECTIVE

Smokers have significantly less cases of neurodegenerative diseases like Alzheimers & Dementia, even in spite of the inflammatory nature of cigarettes (this is likely why smokers still get ALS)

A few neuroprotective mechanisms at play here:

1. nAChR Activation
2. Reduction in brain inflammation
3. Reduction of beta-amyloid plaque
4. BDNF stimulation
5. Mitochondrial protection

Most of these benefits stem from nicotine’s activation of the nicotinic acetylcholine receptors (nAChRs).

Funny enough, the leading Alzheimers drug is nearly identical in mechanism to nicotine (Donepezil)

NICOTINE & IQ

Nicotine has shown to improve performance on standard IQ tests. Studies on long-term cigarette smokers has shown tobacco to diminish IQ.

This is likely due to the pro-inflammatory/ROS inducing nature of smoking

The short-term IQ boost likely comes from nicotine’s ability to increase neural communication efficiency in parts of the brain responsible for cognition & problem solving

APPETITE SUPPRESSION & FAT LOSS

Nicotine activates pro-opiomelanocortin (POMC) neurons. These neurons are crucial for regulating bodyweight, homeostasis, and appetite.

Nicotine influences the melanocortin system (the one we all rave about in regards to sun exposure) & subsequently makes us less hungry.

Some studies have linked to it increasing insulin sensitivity & lowering chronic inflammation in diabetics.

So if you’re looking to shed some lbs, Nicotine’s actually quite useful. Not so much if you’re looking to put on muscle.

Not only does it suppress appetite, but it also seems to be linked to increased lipolysis (fat burning). Effects are amplified when used with caffeine

NICOTINE & ADHD

Multiple studies have linked nicotine with improved attentiveness in ADHD patients, so much so that it was used in conjunction with methylphenidate as first line treatment.

It improves, memory, focus, and attention span. It improves short-term memory, information recall, and reaction time.

Essentially all the things you need to be considered “sharp”

I find this highly effective when doing linear tasks, especially ones that require a bit of fast thinking.

Podcasts, sales calls, meetings, especially writing (I’m zynned up right now)

This is why so many people with ADHD (Hunter Types) self-medicate with nicotine.

It’s the perfect amount of cognitive enhancement & sympathetic nervous system activation to get you dialed.

All while suppressing the part of your brain that's getting you distracted in the first place (Default Mode Network)

It'll also have you thinking less about food

NICOTINE & REACTION TIME

Nicotine shortens your reaction time, both for physical & mental tasks. Study subjects have shown to:

• Answer questions faster (& accurately)
• Hit more targets in a dart game
• Get more correct responses on word recognition
• Increase typing speed

This aspect makes it good for reaction-based sports like baseball, but its vasoconstrictive effects outweigh the speed benefits in terms of physical performance

A 4mg dose was shown to decrease HRV in non-smokers. So maybe don’t pop that 6mg zyn before your next jiu jitsu class

NICOTINE & DEPRESSION

If you’ve ever used nicotine, you know the wave of relief it can give you. A few mechanisms at play here:

• Anti-inflammatory effect
• Dopaminergic effect
• Serotonergic effect (sorry peters)
• Neuroprotective effect
• Endogenous opioid release

Nicotine can either be anxiolytic or anxiogenic (decrease or increase anxiety).

Interestingly enough, its anti-depressant/anxiolytic effects are most profound in ADHD adults. Likely due to the poor cholinergic function found in people w/ ADHD-like symptoms

Dampening the network that reminds you of your worries (default mode network) has a significant anti-depressive effect (why mediation is good for depression)

Its also an analgesic good for short-term pain attenuation

Now lets talk negatives:

- It's toxic in large doses (nicotine sickness)
- It increases stomach acid which can exacerbate GERD/ulcers (don’t take on an empty stomach)
- It can dysregulate blood sugar
- It is linked with developmental issues (don’t smoke if pregnant)

Some studies have linked nicotine (the alkaloid itself) to tumor growth, but this is mainly a concern if you have a strong predisposition

Nicotine also increases the release of glutamate, an excitatory neurotransmitter.

BUT nicotine seems to protect against glutamate-induced excitotoxicity by regulating calcium ion influx & reducing excitotoxic damage (it also releases GABA which is inhibitory)

Now lets talk Erectile dysfunction & hair loss (common nicotine side-effects):

Nicotine is a vasoconstrictor, negatively impacting crucial blood flow to ALL of your organs.

There are other compounds found in tobacco that have vasodilatory effects, as well as a unique mechanism from combusting nicotine, but the inflammatory nature of smoking outweighs this

Every one organs needs ample blood flow to get crucial nutrients & oxygen. Less blood flow = suboptimal function.

So if you’re struggling with hair loss, skin issues, or getting it up, think twice about popping another zyn.

HOW TO USE NICOTINE FOR COGNITIVE ENHANCEMENT

Remember, peak cognitive performance happens in a stimulation window. Not too much, not too little. Just right for the task at hand.

Reserve nicotine for when its actually needed:
• Studying
• Working
• Reading
• Writing

This has dual benefits.

It’ll keep your tolerance down, meaning it has better effect when you need it to but your brain will also start associating the presence of nicotine with doing cognitively demanding tasks.

This in & of itself is where a lot of the benefits come from.

Given its effects on stomach acid, it isn't always ideal to take on an empty stomach. It'll likely have a stronger effect on catecholamine release (like adrenaline).

So try to wait until you have some food in you for a more balanced buzz

IDEAL DOSAGE

The ideal dosage of nicotine is stated at 1-2mg. But in reality, it’s whatever amount that gives you a slightly noticeable buzz without any side effects.

Keep dosage as low as possible to maintain that “sweet spot” of nAChr activation.

Stop consuming nicotine before you get nauseous, dizzy, weak, or any other unpleasant feelings arise. This is a sign of too much nicotine.

You're just overstimulating your cholinergic receptors + CNS. It’ll ramp up your tolerance to no benefit.

Stop before you get sick.

NICOTINE & SLEEP

Nicotine’s a stimulant. It increases alertness & reduces drowsiness. It also releases catecholamines like adrenaline. It will likely interfere with your sleep.

That being said, it’s also my go-to nighttime stimulant.

As long as I stop 30 minutes before going to bed, I have no issue using nic at night. Some people are more sensitive & can notice stimulating effects 2 hours after dosing (nicotine’s half-life).

HOW TO CONSUME

I use nicotine pouches, but thats mainly preference. Other suitable methods (when using for cognitive enhancement) include:

• Patches
• Lozenges
• Gum
• Nasal spray
• Inhaler

Patches will be the most stable delivery & lowest addiction potential

Anything oral will be less habit-forming than vaping/smoking, but is still ritualistic.

If you’ve never consumed nicotine before, any typical dosage will make you sick. Cigs, gum, lozenges, pouch, etc.

If you’re interested to see how you feel on nicotine, use a 1mg patch. It’ll give you a peek at the sensation without overloading your system. Also least habit-forming, but I’d still use caution if you are worried about addiction

Are Zyns bad for you?

I mainly use zyns. They're convenient & discrete. Zyn pouches contain:

• fillers (maltitol + microcrystalline cellulose)
• stabilizer (hydroxypropyl cellulose)
• pH adjusters (sodium bicarbonate)
• nicotine salt
• flavoring
• acesulfame K (sweetener)

One study found zyn contained low levels of ammonia, chromium, formaldehyde, and nickel.

Some other pouch brands actually had traces of uranium in theirs.

These trace contaminants could be the reason behind the peridontal health concern of pouches. But compared to say chewing tobacco, its much less damaging

Ideal? no. Better than tobacco? yes

ZYN ALTERNATIVE:

I recently found a nicotine gum that uses essential oils & xylitol as opposed to synthetics (@nicnacnaturals)

The Xylitol & essential oils contribute to better oral health as opposed to diminishment by zyns

Get some here:
nicnac.com/?sca_ref=43958…

DOSING & FREQUENCY
If you really want to use nicotine to cognitive enhancement, reserve it for cognitively demanding tasks.

Writing, reading, deep work. This will keep your tolerance low & signal to your brain that the presence of nicotine means focus time.

Benefits will be nominal if used habitually.

It’s best used in a cyclical fashion: 4 weeks on 1 week off.

Using different oral stimuli like chewing gum/toothpicks can be a good way to bridge the gap during your tolerance breaks (I find it almost better than nicotine)

"can nicotine make you worse?"

Yes. Bioindividuality is real.

Just because something works for some guy on twitter does not mean it’ll have the same effect for you.

Nicotine is a horrible match for some people depending on the existing state of their CNS. For some it can cause CNS overstimulation.

too much cholinergic activity + reduced noradrenergic activity can lead to depressive symptoms (nicotine can cause both of these).

I benefit from increased cholinergic activity. It's why I spam egg yolks & Alpha GPC. Choline requirements have the highest variation between individuals out of all nutrients.

People with ADHD/hunter type tendencies seem to benefit from increased choline intake (or nicotine).

NICOTINE SYNERGIES

Caffeine & nicotine have gone hand-in-hand for the last 1,000 years.

Studies have shown this combo to potentiate appetite suppression, fat loss, and cognition + energy

L-Theanine will balance the stimulating effects of nicotine & potentiate alpha brain waves further

Rhodiola is another adaptogen that has a balancing synergy with nicotine

ALCOHOL & NICOTINE

Alcohol & nicotine both impact the reward pathways in your brain. Once you start drinking alcohol, your brain interconnects the process with other feel-good activities (like nicotine). So consumption of one triggers the urge for the other.

Nicotine is a game of diminishing returns. If you let your tolerance run rampant, you’ll end up dysregulating your system & just accumulate side effects.

I use nicotine. but I make a deliberate effort to not overdo it

I avoid habitual consumption methods like vape, as the hand-to-mouth repetition is an addictive behavior in & of itself (ritualized)

I keep dosage as low as possible and deliberately take time off

Most importantly, I use nicotine & don’t let it use me. I only allow myself to consume nicotine if I’m actively focusing, writing, or doing deep work.

At this point, my brain has associated the presence of nicotine with deep focus.

If I were to start using nicotine at will, not only would my tolerance skyrocket, but I’d lose that neural association that says nicotine = focus

pros outweigh cons for me. My lifestyle & diet prioritize circulation and I actively monitor my glutamate/GABA balance

I also take tolerance breaks to mitigate downregulation potential

Remember, the dose makes the poison. There is no such thing as a “good” or “bad” compound. Anything that has a strong biological effect in one area will have similarly strong effects in other, unintended areas.

Nicotine has been something I decide to include in my life because I know my biology. I have the opposite of an addictive personality (thanks to a mutation in my DrD4 gene that impacts my dopaminergic response). I frequently drop nicotine cold turkey with no adverse withdrawals

So in short, smoking cigs won’t make you smarter. Ripping zyns 24/7 will have you performing sub-optimally long-term. If you have an addictive personality, tread with caution

If your johnson stops working, your skin is messed up or your hairline’s receding, nicotine is no bueno

Nicotine is an acute cognitive enhancer, but it’s not necessary.

There are plenty of other compounds that can simulate the same benefits & more without addictive properties.

I do not recommend tobacco, and people who haven’t consumed nicotine shouldn't start now, but I believe its important to have the whole picture on a topic as polarizing as this

This is not medical advice. I'm not condoning nicotine use.

Use the compounds don't let it use you

Thanks for reading, share if you found helpful.

Here are links to the studies I got these claims from:

Nicotine & Parkinsons:

Nicotine & default mode network:

Anti-inflammatory effects of nicotine:

Nicotine & Depression:

Nicotine & Athleticism: medicalnewstoday.com/articles/260354
researchgate.net/publication/49…
…nslational-medicine.biomedcentral.com/articles/10.11…
pubmed.ncbi.nlm.nih.gov/16977477/
ncbi.nlm.nih.gov/pmc/articles/P…

Mechanism of Action:

Nicotine & Bodyweight:

Nicotine & lipolysis:

Nicotine & ADHD:

Nicotine & Memory: tobaccoinaustralia.org.au/chapter-6-addi…
ncbi.nlm.nih.gov/pmc/articles/P…
pubmed.ncbi.nlm.nih.gov/8779941/
pubmed.ncbi.nlm.nih.gov/8741955/
pubmed.ncbi.nlm.nih.gov/20414766/

Nicotine & Reaction Time:

Nicotine & HRV:

Nicotine Potentially carcinogenic:

Nicotine up regulates nicotinic receptors: ir.lib.uwo.ca/cgi/viewconten…
pubmed.ncbi.nlm.nih.gov/21350044/
academic.oup.com/toxsci/article…
ncbi.nlm.nih.gov/pmc/articles/P…

Nicotine increases brain functional network efficiency:

Nicotine & IQ:

Nicotine pouches & Oral health:

ADHD-Depression treatment: gwern.net/doc/nicotine/2…
pubmed.ncbi.nlm.nih.gov/7892431/
ncbi.nlm.nih.gov/pmc/articles/P…
ncbi.nlm.nih.gov/pmc/articles/P…