Up in Smoke
The trade-offs of using nicotine as a cognitive enhancer
Nicotine may well be a drug with a thousand faces.
Any good MBA knows that product diversification is central to growing a business. Sure you can inhale nicotine through the smoke of a cigarette, cigar, pipe, or hookah, but for a less conspicuous option, chewing tobacco, snus, dip, and snuff are also available. Big Tobacco would be remiss to leave out those tech-obsessed millennials and Gen Zs. For them, rechargeable e-cigarettes and colorful vapes provide the hit. (“E-cigarettes” and “vapes” interchangeably refer to the same nicotine delivery device.)
The next big thing for nicotine is moving beyond tobacco altogether. Nicotine gums, lozenges, pouches, and toothpicks are now commonly being used as cognitive enhancers or “nootropics.”
We likely have two men to thank for nicotine’s big comeback.
The first is Peter Attia, M.D., a physician focused on longevity whose health advice and insights I otherwise respect. Listeners to his podcast The Drive tend to closely ape his every practice and rush to purchase any supplement he mentions. Although Attia stops short of formally endorsing the use of nicotine, he has spoken openly about his use of nicotine gum and lozenges as a cognitive enhancer over the last ten years. In a recent video he recorded while exercising, Attia even wore a hat prominently sporting the Marlboro logo (he was tone deaf to criticism about the hat, which he stated was commemorative and therefore somehow tolerable).
The second source has likely had an even stronger effect: Andrew Huberman, Ph.D., an associate professor of neurobiology at Stanford University School of Medicine, whose podcast Huberman Lab claims to be the “#1 health podcast in the world.” He discusses numerous topics in science, often with the goal of optimizing various facets of life.
You can easily identify an avid listener of Huberman’s if “dopamine detox,” “cold exposure,” and “physiologic sigh” pop up in conversation. You may also hear ashwagandha, rhodiola, and tongkat ali described as essential life-giving supplements given the high praises sung by a certain mountebank.
A September 2022 Huberman Lab episode addressed nicotine’s effects on the brain and body. Although several methods to stop smoking or vaping were discussed, Huberman could not stop himself from extolling the virtues of nicotine.
[Nicotine] is an excellent tool for enhancing cognitive ability. And of course that triggers my mind to return to the anecdote about my Nobel prize-winning colleague who ingests nicotine by way of nicotine containing gum in order to increase levels of cognitive focus …
Right now, it appears that provided the dosages [of nicotine] are kept reasonable, and we'll talk about what reasonable means a little later, and the frequency is kept relatively low, so not relying on these things constantly, there may in fact be some benefit to ingesting nicotine from time to time, provided that you are not still developing your brain.
Drs. Attia and Huberman are undoubtedly correct: nicotine can greatly improve alertness, attention, and mood, all of which seem to be in short supply in modern-day society. Additionally, the utility of nicotine in treating Parkinson’s disease, depression, and ulcerative colitis is currently being investigated.
As economists love to remind us, however, there is no such thing as a free lunch.
Despite avoiding the myriad ills of tobacco, using nicotine still carries significant risk of psychological and physical addiction as well as the possibility of developing vascular dysfunction and metabolic syndrome.
Moreover, there is a strong argument that the use of non-tobacco nicotine may function as a gateway to other forms of nicotine delivery, including vapes and good ol’ combustible cigarettes.
Nicotine Dependence: a Dance with the Devil
Nicotine replacement therapy (NRT) was first approved for tobacco cessation by the Food and Drug Administration (FDA) in 1984. Since then, NRTs have been shown to increase the rate of smoking cessation by about 50 to 60 per cent. Nicorette, which sells nicotine-based gum and lozenges, and Nicoderm, which sells nicotine patches, are now practically household names.
These brands now have steep competition. Several start-ups are vying for the scores of new customers created by Huberman et al. Lucy Goods and Rogue advertise “nicotine adventures” and “nicotine on demand,” respectively, aiming to make clear that their nicotine products are not your grandfather’s Camels nor your mother’s tacky Nicorette.
As one’s goal is generally not to trade one addiction for another, traditional NRT manufacturers recommend their products are only used for about three months. Individuals who need to use these products for longer than twelve weeks are asked to consult with a healthcare provider.
This is a rare finding in capitalism: a company advising their consumers to stop using their product after a certain amount of time. It runs counter to the very basis of the profit motive.
Those nicotine start-ups, no doubt driven by that same profit motive, proffer no such restrictions on their websites. Lucy Goods instead advertises their products for adults “who take their everyday routines seriously but aren’t satisfied with everyday solutions.” Their 4mg or 6mg strength gum “is more likely to satisfy if you have an everyday nicotine routine.”
To be blunt, an “everyday nicotine routine” is an addiction.
Look no further than Huberman’s acolytes to learn about the severity of nicotine dependence. In one thread addressing the use of nicotine as a nootropic on the Huberman Lab subreddit, these glowing testimonies were recorded:
If you're not addicted already please god don't get into it.
I tried to use nicotine as a nootropic and intended to have strict limits with using it. I found myself craving more and more and decided I need to stop now before I can’t.
I personally wouldn’t want my worst enemy to pick up a nicotine habit. It can take over your life … the feeling of being on your last pouch and in a place where you don’t know if you’ll be able to get another anytime soon is absolutely terrible … all of it just added stress and anxiety and made me feel so much worse. I feel so much better mentally and physically not being tethered to that stupid drug.
Playing with nicotine is like dancing with the devil.
Don’t do it. You do not want to become a slave to nicotine. The nootropic benefits mean nothing if you are addicted.
The addictive qualities of nicotine are so severe that the U.S. Surgeon General deems it comparable to heroin and cocaine.
At present, there is no research regarding how many individuals who use nicotine as a nootropic are interested in quitting and struggle to do so. By way of comparison, close to 70 per cent of cigarette smokers want to stop using tobacco but only about 10 per cent are successful in quitting over a one-year span.
If nicotine is initiated as a nootropic, used habitually, and there is eventual desire to cease usage, these data and brief anecdotes suggest it will be particularly difficult to quit.
Nicotine and Cardiovascular Health
In This is How You Will Die, I explored how chronically elevated blood pressure contributes to the formation of atherosclerotic plaques, which lead to heart attacks, strokes, dementia, and kidney disease.
Acutely, nicotine raises systolic blood pressure (the “top number”) by about 5-10 points, an effect that persists for 90 minutes or longer and likely ceases around 120 minutes.
There is currently little evidence regarding the effects of long-term nicotine use on blood pressure among nicotine-naïve individuals. Some of the only research suggests there is no change in blood pressure after using NRTs for smoking cessation over 45 days, although all participants were former smokers.
Based on anecdotal reports and the quasi-recommendations made by nicotine start-ups, individuals who use nicotine as a nootropic likely do so for longer than six weeks.
Despite the dearth of evidence, I do expect long-term use of nicotine to increase risk of atherosclerotic cardiovascular disease (ASCVD). A short digression into the components of blood pressure is required to understand why.
Conventionally, blood pressure is determined by two factors, cardiac output (CO) and SVR (systemic vascular resistance). In turn, cardiac output (CO) is determined by heart rate (HR) and stroke volume (SV). Formulaically,
BP = CO x SVR
Where CO = HR x SV
SVR refers to the amount of force exerted by the vessels on the blood. One may think of an expanding or contracting water hose: with expansion (or “dilation”), there is less force exerted on the water by the hose; with contraction (or “constriction”), there is more force exerted by the hose.
SV refers to the amount of blood that can be pumped out of the heart into the body with a single heartbeat.
The effect of nicotine to acutely increase systolic blood pressure by 5-10 points stems from both an increase in heart rate (which increases CO, cardiac output) as well as vasoconstriction (increasing SVR, systemic vascular resistance).
If nicotine is used routinely throughout a typical day, one expects blood pressure to remain consistently elevated, mimicking an individual with hypertension at rest. Even with sparing use of nicotine, for instance just two administrations per day, 12 per cent of one’s waking hours are spent in a hypertensive state, assuming they are awake for 16 hours.
Although such granularity likely cannot be modeled in research, it is conceivable that such periodic exposure to the shearing force of elevated blood pressure is sufficient to promote some degree of intimal damage, the forerunner to atherosclerosis.
Separate from any potential effects on blood pressure, nicotine has been shown to alter the ability of blood vessels to dilate effectively and promote adverse vascular remodeling, which each independently increase risk of atherosclerosis.
When nicotine use is paired with other atherogenic conditions, such as chronically high blood sugar and cholesterol levels, the risk of developing atherosclerotic plaques creeps ever higher.
Nicotine and Metabolic Health
Other major contributors to atherosclerosis and overall mortality include poor blood sugar and cholesterol regulation as I also discussed in This is How You Will Die.
Consumption of tobacco has long been acknowledged to blunt appetite and spur weight loss. Experimentally, mice given nicotine decrease body fat as much as 15 to 20 per cent over just 30 days. Cessation of tobacco use, in turn, can cause notable weight gain. NRTs can help to prevent some of this weight gain but do not eliminate it entirely. As such, the use of nicotine on its own should not be deemed a weight loss strategy.
Having normal body weight, which is true of most smokers, is no guarantee that metabolism is not deranged. This is especially true for non-white populations: among Pacific Islanders, the rate of type two diabetes is as high as 18 per cent among those with normal BMI.
Long-term use of nicotine gum has been associated with hyperinsulinemia (a state of chronically elevated insulin due to consistently high blood sugar) and subsequent resistance to insulin, the bedrock of type two diabetes. This relationship explains the observation that while there is weight gain following smoking cessation, there is a decrease in insulin resistance and risk of developing type two diabetes.
Tobacco use is also correlated with increased levels of LDL-cholesterol (LDL-C), a major fuel source for atherosclerotic plaques. In animal models, cigarette smoke inhalation and the administration of nicotine in isolation both led to similar increases in LDL-C, suggesting nicotine greatly influences this result.
Smoking cessation can therefore lead to decreases in LDL-C, but this finding was not reproduced in other work.
Taken together, the use of nicotine as a nootropic may contribute to insulin resistance and increase LDL-C, heightening the risk of ASCVD and overall mortality.
Gum as a Gateway
The COVID-19 pandemic saw a concerning rise in tobacco use and cigarette sales while sales for traditional NRTs decreased. Tobacco use in the United States had previously enjoyed a steady decline over the last five decades.
In addition to the nicotine start-ups mentioned above, cigarettes themselves are attempting a re-brand. Hestia, one of the only new cigarette brands approved by the FDA this century, markets its otherwise normal cigs with the help of memes and influencers on social media. One blogger waxed poetic:
“Smoking cigarettes is extremely important and cool … vaping is only acceptable on like airplanes [note: it is actually firmly illegal] or at work … Lately I’ve been smoking Hestia Cigarettes, they’re not avail in NYC yet but I get them shipped special (free!) to me.”
Whereas e-cigarettes originally appeared discreet and mechanical, they have also undergone a re-brand. Vapes are now bubbly, colorful, and ostentatious, adding notable pop to parties and social media posts.
Health experts have compared the juvenile designs of modern vapes to Joe Camel, a 1990s cartoon that promoted smoking to young adults. In 2022, 14 per cent of American middle and high school students used e-cigarettes, favoring fruit and candy flavors in particular. Other work shows that adolescents who utilize vaping for weight loss vape more frequently, a relationship also observed in adults. (No causal relationship between vaping and weight loss has been established.)
Given the relatively recent rise in utilizing nicotine as a nootropic, there exists no research examining whether this use leads to consumption of other forms of nicotine such as vaping or cigarettes. In the absence of this evidence, my argument can only be structured syllogistically with the following premises:
Nicotine, as noted, is extremely addictive. With habitual use, there is likely to be escalation of intake, as larger amounts of the substance are needed to achieve the intended cognitive effect and avoid the effects of withdrawal.
Escalating intake requires more product to be purchased. In economics, the substitution effect holds that consumers will switch to a cheaper alternative of a given product whenever possible.
The cost of 100 pieces of 4mg nicotine gum is about $30 (a total of 400mg of nicotine). Each Elf Bar vape is about $15 and contains roughly 650mg of nicotine.
Limited evidence finds that e-cigarette usage contributes to later initiation of cigarette smoking.
Epidemiologic evidence suggests that nicotine already functions as a gateway to the use of marijuana and cocaine. The contributory molecular pathways affected by nicotine are also well established.
Thus, given that nicotine is addictive, requires escalation of use, and likely functions as a gateway substance, and that cheaper and appealing alternatives to nicotine gums, lozenges, and pouches exist, there is substantial probability that utilizing nicotine as a nootropic will lead to using other forms of nicotine, which in turn enhance risk of morbidity and mortality.
To be clear: there is no such thing as a free lunch.
Java over Gum
I would be remiss to not address the nootropic with the highest rate of addiction in the world: caffeine. Like nicotine, caffeine also amplifies alertness, attention, and mood. Whereas nicotine may increase risk of ASCVD, moderate caffeine use (three to five cups of coffee per day) is associated with lower risk of cardiovascular disease. Even at a sustained dose of about five cups of coffee per day, systolic blood pressure increases only about 2 points on average.
Although consumption of nicotine alone raises health concerns, the mechanism of delivery also carries attendant risks, including the high temperatures of e-cigarettes causing significant lung injury and the various toxins found in cigarettes.
Conversely, the most common delivery device for caffeine, coffee, likely only has health benefits. As stated elegantly by sleep scientist Matt Walker on the Tim Ferriss Show:
Because most people in developed nations are still deficient in whole food dietary intake, the humble coffee bean has been asked to carry the Herculean weight of all of our antioxidant needs. And that’s why drinking coffee has such a strong statistical health signal in the data when you do epidemiological studies. So it’s not the caffeine that’s related to the health benefits, it’s the antioxidants. Case in point, if you look at de-caffeinated coffee, you get many of the same health [benefits].
The presence of these antioxidants likely explains the association between coffee consumption and decreased all-cause mortality.
Given that caffeine and nicotine are both used for nootropic purposes, there exists a clear preference if one’s goal is also to have a long, enjoyable life.
Although this piece was heavy on proscriptions and moralizing, I nonetheless value the autonomy of individuals to make choices they deem best for themselves given careful assessment of the relevant risks and benefits.
Ultimately, one may prefer to use a nicotine product instead of caffeine as a nootropic. I respect this decision so long as the health risks of nicotine and the likelihood of dependence and escalation of use (requiring further expense and possible substitution to more harmful alternatives) are acknowledged and considered.