Effects of Nicotine on Cognition
Written by Brett Weiss
October 2019
Many who use nicotine products report that it helps them ‘to focus’ and ‘concentrate.’ Research suggests that they may be onto something in that nicotine improves ‘attention’ and ‘working memory’ with acute dosages. To what degree do these improved cognitive capacities result from avoidance of withdrawal symptoms, which associate with reduced ‘attention’ and ‘working memory?’ Aside from the acute benefits of nicotine usage on cognition, what might happen to the brain with long-term use of nicotine products? The following will entail a review of nicotine use on cognition.
Tobacco use disorder (TUD) accounts for some 435,000 premature deaths per year in the U.S. (Valentine & Sofuoglu, 2018). Still, 19.8% of adults in the US are smokers; and smoking is disproportionately common among people of low socioeconomic status, low educational background, and with psychiatric comorbidities (Valentine & Sofuoglu, 2018). People reporting that nicotine use helps them to ‘stay focused’ stems from avoidance of cognitive deficits and negative effects that come from nicotine withdrawal along with potential short-term cognition enhancing effects. Smoking abstinence gives a subjective experience with difficulty concentrating, reduced attention, and impaired working memory (Valentine & Sofuoglu, 2018).
People with psychiatric disorders have a 70% higher chance of becoming a smoker than the general population (Campos et al., 2016). People with psychiatric disorders also have symptoms that include deficits in attention, working memory impairment, along with response inhibition dysfunction (response inhibition refers to the ability to suppress actions in a given context that interfere with goal-directed behavior) (Valentine & Sofuoglu, 2018). Hence, cognition-enhancing effects of nicotine may especially contribute to higher prevalence of smoking in the population with psychiatric disorders.
With health concerns from nicotine use resulting in premature death and with known highly addictive properties of nicotine, why would people start using nicotine in the first place? The answer to this question may come from possible cognition-enhancing acute effects of exposure to nicotine. Nicotine acts on nicotinic acetylcholine receptors, which have widespread distribution throughout the brain. Nicotinic acetylcholine receptor activation through nicotine affects a wide array of neurotransmitter systems, including norepinephrine, serotonin, and dopamine (Campos et al., 2016). The neurotransmitter systems that nicotine affects have an impact on sensory systems, motor systems, attention, executive function, learning, and memory (Campos et al., 2016). Through actions on nicotinic acetylcholine receptors and subsequent neurotransmitter systems, acute dosages of nicotine confer temporary cognitive improvement in attention, verbal memory, working memory (short-term memory), and executive function in non-smokers (Campos et al., 2016). The initial cognition-enhancing effects along with the rewarding sensations of nicotine use facilitate chronic usage. Chronic usage of nicotine associates with cognitive impairment and decline in middle age (Campos et al., 2016).
Some mechanisms through which researchers believe chronic usage contributes to cognitive impairment and decline include reduced neurogenesis, oxidative damage to biological macromolecules in the brain, and triggering of an inflammatory cascade that leads to many diseases in the central nervous system with memory impairment (Campos et al., 2016). The finding that chronic use of nicotine correlates with suppressed generation of new neurons from the dentate gyrus of the hippocampus (suppressed neurogenesis), means that depression and cognitive impairment may result. New neurons from the hippocampus, a region that plays a pivotal role in learning and memory, contribute to formation of new memories along with structural integrity of the brain. Hence, the totality of effects of suppressed neurogenesis from chronic exposure to nicotine remain unknown.
Nicotine acts on the nicotinic acetylcholine receptors of the brain to facilitate addiction and chronic usage. Nicotinic acetylcholine receptors have five components as pentamers, consisting of combinations of 12 subunits. The subunits consist of α2-α10 and β2-β4, which genes CHRNA2–10 and CHRNB2–4 encode, respectively (Herman & Sofuoglu, 2010). The acetylcholine receptor subunits mediating cognitive effects of nicotine include α2, α3, α4, α5, α7, β2, and β4, with the strongest evidence for involvement of α7 and β2 subunits in cognitive effects (Valentine & Sofuoglu, 2018). Clinically, nicotinic acetylcholine receptors with all five subunits consisting of α7 subunits (homomeric α7 nicotinic acetylcholine receptors) play a role in cognitive deficits in many neuropsychiatric disorders, including Alzheimer’s disease, Parkinson’s disease, autism spectrum disorder, and schizophrenia (Valentine & Sofuoglu, 2018). For instance, α7 nicotinic acetylcholine receptors have been implicated in sensory gating dysfunction in schizophrenia (Valentine & Sofuoglu, 2018). Sensory gating refers to ability to separate meaningful from irrelevant information and may play a role in sensory overload and cognitive deficits seen in schizophrenia. In post-mortem tissue of patients with schizophrenia, researchers have found a reduction in α7 nicotinic acetylcholine receptors in hippocampus (region in brain involved in learning and memory) in comparison to neurotypical individuals (Valentine & Sofuoglu, 2018). Giving pharmaceutical agents that activate α7 nicotinic acetylcholine receptors (agonists) to patients with schizophrenia reverses sensory gating deficits and helps with smoking cessation (Valentine & Sofuoglu, 2018). Accumulating evidence implicates the β2 subunit of nicotinic acetylcholine receptors in cognitive effects of nicotine as mice that lack this subunit (genetically modified knock-out mice) exhibit deficits in working memory, attention, inhibitory control, and behavioral flexibility (Valentine & Sofuoglu, 2018). Mice lacking this subunit do not show memory enhancement (associative memory performance) from nicotine, either (Valentine & Sofuoglu, 2018). Furthermore, medications stimulating α4β2 nicotinic acetylcholine receptors have cognition enhancing effects. One such example, varenicline (also called Chantix), improves learning deficits from nicotine withdrawal and improves cognitive function in humans (Valentine & Sofuoglu, 2018). The effects of nicotine on nicotinic acetylcholine receptors result in effects on cognition through influencing neurotransmitter systems.
The dopamine neurotransmitter system modulates many cognitive functions, such as working memory, attention, and response inhibition (Valentine & Sofuoglu, 2018). The activation of nicotinic acetylcholine receptors in dopaminergic neurons in the brain contribute to the rewarding and cognition enhancing effects of nicotine (Valentine & Sofuoglu, 2018). The precise role through which the dopamine system mediates cognitive effects through nicotine usage has yet to be determined, though.
Nicotine also has major effects on the glutamate neurotransmitter system. Glutamate neurotransmitters play major roles in learning and memory along with neuronal excitation. The medial habenula, a brain structure below the cerebral cortex toward the middle of the brain, produces mostly glutamate (Picciotto & Kenny, 2013). At the same time, it also produces the neurotransmitter acetylcholine which activates nicotinic acetylcholine receptors in nicotine and non-nicotine users. The medial habenula contains some of the highest densities of nicotine binding sites in the brain (Picciotto & Kenny, 2013). Recent studies suggest that nicotinic acetylcholine receptors expressed in the medial habenula regulate addictive actions of nicotine (Picciotto & Kenny, 2013).
The acute cognition-enhancing effects of nicotine facilitates the powerful changes of chronic nicotine usage on brain chemistry and overall health. Through binding to nicotinic acetylcholine receptors throughout the brain to modulating neurotransmitter and sensory systems, nicotine has profound addictive properties. Individuals with psychiatric comorbidities have a much higher chance of turning to nicotine to compensate for potential cognitive impairments. Perhaps researchers need a more detailed and comprehensive understanding of cellular pathways and neurotransmitters systems involved in cognition enhancement from nicotine in order to improve cognition in people without harmful effects of cigarette smoke. Alternatively, perhaps the cellular pathways and neurotransmitter systems involved in nicotine cognition enhancement and addiction are best left unaltered throughout one’s lifetime. Afterall, once disrupted, the cellular pathways and neurotransmitter systems never fully return to their original state! For example, once the dopamine neurotransmitter system undergoes alterations through nicotine use, it never returns to its original, inherited state of attaining balance or homeostasis. In other words, the cognition enhancing benefits of nicotine come with a heavy price with or without the ill effects of tobacco smoke. Understanding the neurochemical pathways involved in nicotine usage will also help in designing pharmaceuticals to help people quit using.
References
Campos MW, Serebrisky D, & Castaldelli-maia JM (2016). “Smoking and Cognition.” Curr Drug Abuse Rev. 9(2): 76–79.
Herman AI & Sofuoglu M (2010). “Cognitive Effects of Nicotine: Genetic Moderators.” Addict Biol. 15(3): 250–265.
Picciotto MR & Kenny PJ (2013). “Molecular Mechanisms Underlying Behaviors Related to Nicotine Addiction.” Cold Spring Harb Perspect Med. 3(1): a012112.
Valentine G & Sofuoglu M (2018). “Cognitive Effects of Nicotine: Recent Progress.” Curr Neuropharmacol. 16(4): 403–414.
