Nicotine: A Powerful Nootropic, but at What Cost?

Nicotine clearly enhances cognitive function ¹, but the long-term health effects of nicotine use are less well known. This post is a cost-benefit analysis of nicotine use for nootropic purposes.

By definition, a nootropic cannot cause significant harm. Thus even classifying nicotine as a nootropic presupposes its safety.

The acute cognitive enhancing effects of nicotine are robust and well-documented. I’ve used sublingual nicotine myself with good results.

Nicotine may also decrease the risk of developing Parkinson’s disease [ref]. But what about the consequences of chronic nicotine use?

It's possible that nicotine might provide a short-term boost but have negative effects down the line. Even worse, because nicotine can acutely improve memory, it might mask the negative effects that accrue from long-term consumption.

That's precisely why the negative effects of nicotine require clarification.

Addictiveness of Pure Nicotine

The long-term health effects of habitual nicotine use are controversial.

What is not controversial is that nicotine replacement (via vaporizer, transdermal patch, gum or lozenge) is a safer alternative to cigarette smoking and is an extremely effective harm reduction strategy for ex-smokers.

It's important to recognize the distinction between nicotine and tobacco. Nicotine is a parasympathomimetic alkaloid and nicotinic acetylcholine receptor agonist.

Tobacco is a mixture of thousands of compounds, many of which are carcinogenic, cardiotoxic, teratogenic or all three. To better appreciate this distinction, I recommend reading a great article about nicotine (and the nootropic properties of nicotine) on Gwern.net.

It is frequently claimed that nicotine is as addictive as heroin, when in fact what is meant is that tobacco is as addictive as heroin. In animal models, it is notoriously difficult to induce nicotine dependence or addiction. Monoamine oxidase (MAO) inhibitors, which are present in tobacco smoke (e.g., continine), have been reported to potentiate the addictive potential of nicotine. This may be one factor that accounts for the disparity in the addictiveness of pure nicotine verses tobacco.

In the two tables below, we will consider both the health benefits of nicotine and its deleterious effects. The scientific literature is very polarized about the impact of nicotine on health. On the one hand, neuroscientists have argued that nicotine is the only substance in existence that reliably enhances working memory and general cognitive performance.

Nicotine may also mitigate the risk of neurodegenerative disease (referred to in the literature as the “smoker’s paradox“). Also, nicotine ameliorates symptoms of Alzheimer’s disease and is tentatively an effective treatment for depression.

(Brief aside: the relationship between nicotine and depression is a little murky. On the one hand, nicotine has been noted to reverse some of the cognitive deficits associated with depression. On the other hand, tobacco smoking is linked to suicide and depression. The direction of causality is not clear: are individuals with depression predisposed to smoke, or does smoking itself exacerbate depression? Since nicotine is a cholinergic drug and excess acetylcholine signaling is also linked to depression, it’s certainly possible that nicotine might worsen depression.)

Nicotine Safety & Negative Effects

Nicotine may decrease hippocampal neurogenesis (the birth of new neurons in the brain). This population of neurons play an important role in resilience to depression as well as learning and memory.

• Effects of nicotine on neurogenesis and plasticity of hippocampal neurons [2005]

Nicotine may similarly impair synaptic plasticity in a dose-dependent fashion. (Synaptic plasticity refers to the ability of synapses to strengthen or weaken over time, in response to increases or decreases in their activity.)

Finally, studies have also reported that nicotine adversely affects the cardiovascular system by enhancing sympathetic tone, inducing vasoconstriction, increasing blood pressure, and heart contractility. (The sympathetic nervous system is what is responsible for the fight-or-flight response).

These negative effects of nicotine on the heart (cardiotoxicity) are also controversial. For example, researchers reported that “nicotine is not a significant risk factor for cardiovascular events” (ref), and is safe to use even in high-risk populations like patients with coronary artery disease (ref).

Other Ill Health Effects of Nicotine

• Mechanisms for nicotine in the development and progression of gastrointestinal cancers [2012]

Nicotine may decrease insulin sensitivity.

• Long-term use of nicotine gum is associated with hyperinsulinemia and insulin resistance [1996]
• Activation of AMPKα2 in adipocytes is essential for nicotine-induced insulin resistance in vivo [2015]

Nicotine may impair neuroprotection.

• Oral contraceptives and nicotine synergistically exacerbate cerebral ischemic injury in the female brain [2013]
• Nicotine appears to decrease the neuroprotective role of estrogen in both sexes (see Examine.com entry section 11.2) and New evidence of mitochondria dysfunction in the female Alzheimer’s disease brain: deficiency of estrogen receptor-β [2012] as hypothetical concern.
• Nicotine pre-exposure reduces stroke-induced glucose transporter-1 activity at the blood-brain barrier in mice [2015]

Nicotine may be bad for the renal organ system (kidneys).

• Nicotine signaling and progression of chronic kidney disease in smokers [2013]

Nicotine may have carcinogenic effects:

• Nicotine appears to have carcinogenic metabolites produced in human saliva. Adequate Vitamin C is suggested to counteract. ref1 ref2
• α5-nAChR modulates nicotine-induced cell migration and invasion in A549 lung cancer cells [2015]
• Nicotine upregulates microRNA-21 and promotes TGF-β-dependent epithelial-mesenchymal transition of esophageal cancer cells [2014]
• Nicotine induces tumor growth and chemoresistance through activation of PI3K/Akt/mTOR pathway in bladder cancer [2015]
• Role of vitamin C and selenium in attenuation of nicotine induced oxidative stress, P53 and Bcl2 expression in adult rat spleen [2014]

Nootropic Effects of Nicotine

Harmful Effects of Nicotine On Brain Function

My Verdict on Nicotine

I’ve used nicotine with good results. It’s one of the few nootropics that tangibly improves my working memory.

However, there are some serious trade-offs with nicotine. My attitude toward nicotine is analogous to how I view phenibut. Both should be used sparingly, and chronic, daily use should be avoided.

From a brain health perspective, most of the negative effects of nicotine are on the developing brain. (Your brain is technically still developing until the end of adolescence, around age 25). But on the other hand, nicotine has a protective effect against Parkinson’s disease and has some anti-dementia properties as well. The cost/benefit ratio for nicotine gets favorable the older you are.

Despite the negative effects of nicotine, I'll continue to use it on a bi-weekly basis for a boost in lucidity.

Appendix

Are Vape Pens Bad For You?

It is generally believed that vaping poses no substantial risk to one’s health. A recent study published in the May 2015 edition of Addiction reported that e-cigarettes generate high levels of aldehydes only in “dry puff” conditions.

Aldehydes are toxic organic compounds that can be emitted by electronic cigarettes due to thermal decomposition of liquid components. One of the primary arguments that vaping is unhealthy was based on the deleterious effects of aldehydes. Until now, the functional significance or relevance of true exposure to aldehydes from vaping has remained unclear. This study clarifies the issue, finding that significant levels of aldehydes are only emitted in special circumstances – during dry puffs.