For the past few months I’ve been experimenting with nicotine as a nootropic. A nootropic substance is one that improves cognitive function without any harmful effects, and ideally is non addictive and non habit forming. A lot of nootropics do not have hard science backing them up. Nicotine is one of the very few that has scientific literature showing general cognitive benefits.

Is it addictive?

Cigarette smoke contains over 5,000 compounds, but in popular discourse nicotine gets all the attention as the ‘thing that makes cigarettes addictive’. The widespread belief that nicotine alone causes cigarettes to be addictive is due to an influential 640 page report entitled “ The Health Consequences of Smoking: Nicotine Addiction ” that was released in 1988 by the U.S. Surgeon General. The report leads with the summary statement that “Nicotine is the drug in tobacco that causes addiction”, and goes on to suggest that nicotine is similar in its level of addictiveness to heroin. Today this report is viewed as flawed, because it drew on studies of tobacco use to establish the addictiveness of nicotine, rather than studies on nicotine in isolation. In the intervening years, marketing hype around nicotine replacement products for smoking cessation has kept the focus on nicotine as ‘the solution’ to getting cigarette users to stop smoking. More recently, people have promoted E-cigs as a path to smoking secession, an idea which remains very controversial, [ref, ref] but is promising from a harm reduction perspective.[ref, ref] Because they deliver nicotine quickly to the brain, e-cigs are one of the most addictive methods of nicotine delivery.

A large meta-analysis found that nicotine replacement products (NRP) increased the likelihood of quitting smoking by 50-70%[ref]. However, the base rate for being able to quit cigarettes during any multi-month program remains low (~5 %??), and the number of people who are able to quit after NRP program is likewise low (~10-20%)[ref]. These stubbornly low rates of success have lead some researchers to wonder if something else is making cigarettes addictive. Recent research suggests that the addictiveness of cigarettes may be due to an interaction between MAOIs (which are found in tobacco smoke) and nicotine. Gwern’s writeup contains much more discussion and extensive references on this point.

In response to the focus on nicotine as the cause of smoking’s addictiveness, Frenk and Dar wrote a 241 page monograph, “ A Critique of Nicotine Addiction ” (2002). As Gwern notes, the authors generally overstate their case by trying to argue that nicotine is not addictive at all. The general consensus is that nicotine is addictive.

Animals, including rats and squirrel monkeys, will self administer nicotine. Nicotine addiction appears to occur through the dopamine system – killing the dopaminergenic neurons in animal models leads to a cessation of self-administration. Interestingly, the dose-response curve of nicotine quickly flattens out in rats — ie. they will quickly self limit how much they are taking. This is in contrast to drugs such as cocaine or amphetamines. Nicotine intake in humans usually lies in a narrow range , between 2-30 mg per day.

The addictiveness of nicotine is modulated by the intensity and duration of nicotine exposure. In general with addictive substances, the more quickly it is delivered, the more dopamine and reward substances are produced. The brain contains mechanisms for for tolerance/habituation, to prevent too many reward compounds from being produced, but when nicotine is delivered quickly, the brain just doesn’t have the time to develop tolerance. Another reason that fast delivery (ie. through vaping / smoking) is more addictive than other methods of intake is that it easier for you brain to associate the reward to the act of smoking / inhaling. Nicotine enters the brain only 10-20 seconds after a person takes a draw from a cigarette. Finally, nicotine receptors sensitize and desensitize fairly quickly.



Optimal dosing and delivery method for nootropic benefit

A cigarette administers about 2 mg of absorbed nicotine. As a nootropic, limiting to 1-2mg a day is recommended.

Delivery methods: risk for addictiveness from highest to lowest:

Vaping Nasal nasal spray Nicotine inhaler Nicotine mouth spray Chewing gum (when properly taken) Lozenges (when properly taken, do not chew) Nicotine patches [these administer nicotine over hours, resulting in significantly lower chance of addiction than all the above, but on the flip side some users report not seeing as much cognitive benefits]

One study of nicotine gum users concluded “Among long-term users (>/=90 days), 20% attributed their use to addiction… Combining the results of Studies 1 and 2 with other data suggests very few gum users develop dependence on the gum.” [ref] Nicotine gum / lozenges should not be consumed quickly, the packaging recommends ‘parking’ the gum/lozenge under your lip and letting it sit there for a while.

My personal observations

I got the idea to take nicotine as a nootropic after reading an interview with Oxford transhumanist philosopher Nick Bostrom. When asked if he has ever taken any cognitive enhancers, he said he experimented with nicotine gum. In his book Superintelligence he also mentions that nicotine gum helped him write the book.

I have developed a somewhat more nuanced view on addiction. Firstly, if one goes to the level of biochemistry and neurotransmitters, one can draw important distinctions between ‘addiction’, ‘habit’, and ‘dependence’. For instance, SSRIs carry a large dependence but are technically not addictive in the same way that hard drugs are. Technically, addiction can be distinguished from mere habit by the activation of particular reward circuitry in the brain that involves a compound called ‘delta FOS-b’, among other things. But for the purpose of this discussion, we will consider ‘addiction’ to just mean habit and dependence that is really hard to break. An important point when considering nootropics is to understand that addiction, construed in the general sense, is not necessarily a bad thing. For instance, many of us find that the benefits of caffeine outweigh the dependence it entails. The same may hold for more extreme nootropics that are known to be addictive, such as modafinil. As another example, many people find SSRIs and other psychiatric medications useful even though they have a very large dependence. Moving outside the realm of things you ingest, someone might be ‘addicted’ to video games, but video games can provide a good cognitive workout and even facilitate social interaction in some individuals. There are may examples of addictive things that can be net beneficial on one’s health and wellbeing – sex, exercise endorphins, eating healthy, etc. Of course, balance is key, and one must be mindful of the downside – withdrawal symptoms when one does not get their ‘fix’.

Personally, I took nicotine gum at the level of 2 mg / day from January – April, and 1 mg / day from May – June (a single cigarette contains about 2 mg of nicotine). I started noticing dependency after a few weeks of use. I did not take the entire dose at once, I chewed nicotine gum strategically through the day 3-4 times a day, often taking the gum out of my mouth and putting it back in the wrapper. The effects of nicotine are immediately apparent. The withdrawal symptoms are very subtle – there were days where I forgot to take nicotine where I didn’t notice any detrimental effects. The withdrawal became apparent when I tried to do something that requires focus or attention before taking my dose for the day. It was if I had run into a ‘block’ that prevented my mind from functioning at the level I wanted. In my view, the level of dependence feels like a caffeine dependence at the level of 2 mg / day, but more subtle. Additionally, from what I have read, when it comes to quitting, the withdrawal from nicotine can be really protracted (ie a week or longer), while withdrawal effects from caffeine generally only last a few days.

The main problem I’ve had with nicotine is forgetting to bring it with me somewhere, having anxiety about not having it on hand and then having trouble focusing on some cognitively demanding task. It is unclear to me how much of my difficulty came from psychosomatic effects vs actual withdrawal symptoms, however.

While overall taking nicotine on a regular basis has been helpful for me, one should be aware of the dependency downsides and the fact it is harder to ween off than caffeine. However, given that one is dedicated enough, it is possible to ‘taper off’ by simply chewing slightly less each day and for less time.

Some notes on nicotine’s pharmacological effects

Nicotine increases neurotransmitter levels across the board, including catecholamines (dopamine, adrenaline, and nonepinephrine), beta enorphines, seratonin, and even cortisol, the stress hormone, which may not be so good a thing. [ref] See Wikipedia article for detailed refs.

It also increases acetylcholinesterase, the enzyme that breaks down acetylcholine, [ref]

It has a half life of 1-2 hours.

The binding cite with the highest affinity to nicotine is the alpha-4-beta-2-nicotinic receptor. Interestingly, stimulation of this binding site results in increases in human growth hormone secretion.

Nootropic Benefits

Other misc benefits

Risks / things to be aware of

Further reading (and sources with lots more references)