Nicotine, the Brain and Memory

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1. The Papers
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The Papers (29)

Newest first. Study types on this page — Human trial: 4 · Review: 19 · Animal study: 5 · Cell study: 1. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.

Nicotine on the developing brain

Review, 2023. This review gathers research in people and in laboratory animals on how nicotine affects the brain when exposure happens during pregnancy or the teenage years, periods when the brain is still developing and especially easy to change. The authors report that nicotine exposure in these windows harms heart and breathing function, learning and memory, decision-making and planning skills, and the brain's reward circuits. They also describe effects that last into adulthood, including lasting changes to how genes are switched on that can be passed to later generations. The authors note that non-smoked nicotine products are widely used by pregnant women and teenagers because people wrongly believe they are safe.

Castro EM, Lotfipour S, Leslie FM (2023). Nicotine on the developing brain. Pharmacol Res. — PubMed PMID: 36868366 · doi:10.1016/j.phrs.2023.106716

Unique, long-term effects of nicotine on adolescent brain

Review, 2020. This review looked at research on how nicotine affects the brain during the teenage years, a period when brain systems for motivation and thinking are still developing, and compared effects by age and sex. Animal studies show that nicotine has unique effects on the adolescent brain, both short-term and long-term, including effects on reward, aversion, thinking and emotion. Experiments like these cannot be done in people, but a growing body of observational research in humans suggests similar effects across species. The authors conclude there is substantial evidence for a long-term negative impact of teenage nicotine exposure on the brain and behavior, and call for long-term follow-up of teen and young adult e-cigarette users.

Leslie FM (2020). Unique, long-term effects of nicotine on adolescent brain. Pharmacol Biochem Behav. — PubMed PMID: 32738256 · doi:10.1016/j.pbb.2020.173010

Attention-enhancing effects of propranolol and synergistic effects with nicotine

Human trial, 2020. This randomized trial tested nicotine (a 7 mg/24 h skin patch) and the blood-pressure drug propranolol (40 mg by mouth), alone and together, in 26 nonsmokers. Each person had four test days: double placebo, nicotine only, propranolol only, and both drugs, followed by attention tests. Neither drug alone changed hit rate on a sustained-attention task, but together they worked synergistically to reduce the drop in performance over time. Propranolol by itself improved accuracy and reaction time on a change-detection task and raised self-reported vigor, which was the opposite of what the researchers expected; they concluded that nicotine's release of noradrenaline, acting on beta receptors, appeared to limit nicotine's performance-enhancing effects.

Hahn B, Olmstead CK, Yuille MB et al. (2020). Attention-enhancing effects of propranolol and synergistic effects with nicotine. Cogn Affect Behav Neurosci. — PubMed PMID: 32405757 · doi:10.3758/s13415-020-00794-5

Neuropeptide CART prevents memory loss attributed to withdrawal of nicotine following chronic treatment in mice

Animal study, 2019. This study was done only in mice. It looked at why stopping nicotine after long-term use causes memory problems. Mice given nicotine for 49 days did as well as usual on an object-recognition memory test. Eight hours after the nicotine was stopped their memory dropped sharply, and it was fully back by 24 hours. Levels of CART, a brain peptide that supports memory, fell in the memory centre of the brain (the hippocampus) at 8 hours and rose strongly by 24 hours. Giving CART directly into the hippocampus prevented the memory loss at 8 hours, and blocking CART slowed the recovery at 24 hours. The researchers also found nicotinic receptors of the α7 type on these CART nerve cells, which suggests nicotine-related signals reach them directly.

Borkar CD, Sagarkar S, Sakharkar AJ et al. (2019). Neuropeptide CART prevents memory loss attributed to withdrawal of nicotine following chronic treatment in mice. Addict Biol. — PubMed PMID: 29193459 · doi:10.1111/adb.12579

Cognitive Effects of Nicotine: Recent Progress

Review, 2018. This review looks at recent research on how nicotine affects thinking and memory, drawing on both animal studies and human studies. It reports that nicotine can sharpen attention, working memory, fine motor skills and memory for events, and that specific parts of the brain's nicotine receptors (the alpha4, beta2 and alpha7 subunits) are involved in these effects. The authors suggest these effects on thinking may help explain why people start and keep smoking, especially people who already have problems with attention or memory. Because poor thinking skills before quitting predict going back to smoking, they suggest that treatments aimed at improving thinking skills might help people quit tobacco.

Valentine G, Sofuoglu M (2018). Cognitive Effects of Nicotine: Recent Progress. Curr Neuropharmacol. — PubMed PMID: 29110618 · doi:10.2174/1570159X15666171103152136

Dorsal-CA1 Hippocampal Neuronal Ensembles Encode Nicotine-Reward Contextual Associations

Animal study, 2017. This study in freely moving mice looked at how a memory area of the brain called the hippocampus links nicotine's rewarding effect to the place where the animal received it. Researchers used live imaging of brain cells while the mice developed a preference for the place where they had been given nicotine. They found that specific groups of nerve cells in one part of the hippocampus (dorsal CA1) came to encode memories that connected nicotine reward with that place. These cell groups were needed for the mice to show the place preference. These results are from mice only.

Xia L, Nygard SK, Sobczak GG et al. (2017). Dorsal-CA1 Hippocampal Neuronal Ensembles Encode Nicotine-Reward Contextual Associations. Cell Rep. — PubMed PMID: 28591584 · doi:10.1016/j.celrep.2017.05.047

Effects of nicotine on response inhibition and interference control

Human trial, 2017. This randomized, double-blind, placebo-controlled study gave 44 healthy adult non-smokers a 7 mg nicotine skin patch and a placebo patch on separate occasions. Each time they completed a set of attention and self-control tasks, including tasks that measure how well a person can stop an action or ignore distractions. On nicotine, people reacted faster on a simple eye-movement task and on correct responses in a sustained-attention task. Nicotine did not improve the ability to stop an action or ignore distractions on any task, and it made distraction worse on one task.

Ettinger U, Faiola E, Kasparbauer AM et al. (2017). Effects of nicotine on response inhibition and interference control. Psychopharmacology (Berl). — PubMed PMID: 28150023 · doi:10.1007/s00213-017-4542-8

Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products

Review, 2017. A group of scientists from several fields reviewed human and animal research on what nicotine does to the body during pregnancy and adolescence. They concluded that nicotine plays a major part in the harms of tobacco exposure before birth. Those harms include weaker lung function, problems processing sound, poorer heart and breathing function in infants, and possibly thinking and behaviour problems later in life. In teenagers, nicotine exposure was linked to weaker working memory and attention, problems processing sound, and more impulsivity and anxiety. Recent animal studies also suggest that nicotine may make later addiction to other drugs more likely. The authors judged the evidence strong enough to call for public health measures that protect pregnant women, children and adolescents from nicotine.

England LJ, Aagaard K, Bloch M et al. (2017). Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products. Neurosci Biobehav Rev. — PubMed PMID: 27890689 · doi:10.1016/j.neubiorev.2016.11.013

Smoking and Cognition

Review, 2016. This review looks at research on how nicotine affects thinking skills such as attention, learning, memory and movement, by acting on nicotine receptors spread widely through the brain. It reports that nicotine can briefly improve some parts of attention and memory in smokers, and that it also relieves the drop in thinking skills smokers have when they go without nicotine. The authors say both effects reward continued use and add strongly to nicotine dependence, while heavy smoking is linked to poorer thinking and mental decline in middle age. They conclude there is not yet enough data to reach firm conclusions, and that future research should study how these effects matter in treatment to help people quit smoking.

Campos MW, Serebrisky D, Castaldelli-Maia JM (2016). Smoking and Cognition. Curr Drug Abuse Rev. — PubMed PMID: 27492358 · doi:10.2174/1874473709666160803101633

Object recognition memory in zebrafish

Animal study, 2016. This study used zebrafish to test recognition memory: the fish were shown two identical objects, then later shown one familiar object and one new object. Unlike rodents, zebrafish spent more time with the familiar object, but this preference disappeared after a 5-minute delay. Giving the fish nicotine in their water (50 mg/L) before showing them the objects brought the preference back, which the authors read as a memory-enhancing effect of low-dose nicotine. These results come from fish only, and the effect showed up only when the objects were a medium size (2 × 5 cm).

May Z, Morrill A, Holcombe A et al. (2016). Object recognition memory in zebrafish. Behav Brain Res. — PubMed PMID: 26376244 · doi:10.1016/j.bbr.2015.09.016

Nicotine Administration Attenuates Methamphetamine-Induced Novel Object Recognition Deficits

Animal study, 2015. This study used adolescent and adult male rats to test whether nicotine could reduce memory problems caused by high doses of methamphetamine. The rats drank water containing nicotine for several weeks, either before or after receiving methamphetamine. Nicotine lessened methamphetamine's harm to the rats' ability to recognize a new object, but it did not reverse the damage methamphetamine did to the brain's serotonin system. The researchers found that nicotine increased a type of nicotinic receptor in memory areas of the brain, and they suggest this may be how it protected memory. These results come from rats only.

Vieira-Brock PL, McFadden LM, Nielsen SM et al. (2015). Nicotine Administration Attenuates Methamphetamine-Induced Novel Object Recognition Deficits. Int J Neuropsychopharmacol. — PubMed PMID: 26164716 · doi:10.1093/ijnp/pyv073

Nicotine and the adolescent brain

Review, 2015. This review looks at why the teenage brain responds to nicotine differently from the adult brain, using findings from both laboratory animals and people. The authors explain that the brain areas behind memory, decision-making, reward and emotional control are still being reorganized during adolescence. Nicotinic acetylcholine receptors, which nicotine acts on, help guide that development. The authors report that nicotine from tobacco or e-cigarettes during this period can cause lasting changes in brain signaling and thinking, and they argue it may cause epigenetic changes that make the brain more sensitive to other drugs and to later substance abuse.

Yuan M, Cross SJ, Loughlin SE et al. (2015). Nicotine and the adolescent brain. J Physiol. — PubMed PMID: 26018031 · doi:10.1113/JP270492

Nicotinic receptors, memory, and hippocampus

Review, 2015. This review chapter looks at how nicotine and the nicotinic receptors it acts on affect learning and memory in the hippocampus, a brain region important for memory. It draws on studies that gave nicotine once or over a long period, studies using drugs that switch these receptors on or block them, studies in genetically modified mice, and molecular work. The studies it covers suggest that a single dose of nicotine generally improved hippocampus-dependent learning, while stopping nicotine after long-term use led to memory problems. The authors also report that different types of nicotinic receptors (low-affinity and high-affinity) play different roles in these effects.

Kutlu MG, Gould TJ (2015). Nicotinic receptors, memory, and hippocampus. Curr Top Behav Neurosci. — PubMed PMID: 25655890 · doi:10.1007/978-3-319-13665-3_6

Nicotinic alteration of decision-making

Review, 2015. This review looks at how nicotine changes the way people make decisions in general, including choices that have nothing to do with cigarettes, with a focus on impulsivity and risk-taking. The authors describe how long-term nicotine exposure can reshape brain circuits, which is part of how habits around nicotine use form. They note that the experimental evidence is sparse and often contradictory. The review discusses the role of the brain's nicotinic acetylcholine receptors and their subunits, and links these findings to computer models of attention, valuation and action.

Naudé J, Dongelmans M, Faure P (2015). Nicotinic alteration of decision-making. Neuropharmacology. — PubMed PMID: 25498234 · doi:10.1016/j.neuropharm.2014.11.021

Substance abuse, memory, and post-traumatic stress disorder

Review, 2014. This review looks at research on how three commonly misused drugs, nicotine, cocaine and alcohol, affect learning and memory, and how that matters for post-traumatic stress disorder (PTSD). The authors explain that the effects depend on the drug, on whether it is used once or over a long time, and on whether the person is under the drug's influence while learning or being tested. They describe how these drugs interact with the way fearful memories are formed, strengthened and later unlearned. They conclude that these drugs may play a harmful role in the development, persistence and treatment of PTSD, and may get in the way of PTSD treatment.

Tipps ME, Raybuck JD, Lattal KM (2014). Substance abuse, memory, and post-traumatic stress disorder. Neurobiol Learn Mem. — PubMed PMID: 24345414 · doi:10.1016/j.nlm.2013.12.002

Neurocognitive endophenotypes in schizophrenia: modulation by nicotinic receptor systems

Review, 2014. This review looks at why people with schizophrenia smoke much more often than the general population, and whether nicotine and the brain's nicotinic acetylcholine receptors help explain it. Thinking and memory problems affect about 80% of patients with schizophrenia, and the authors describe evidence that these patients' nicotinic receptor system does not work normally. Earlier research, including animal and laboratory studies, found that nicotine affects several brain chemical messengers, including dopamine, glutamate and GABA. In patients with schizophrenia, giving nicotine improved reaction time, spatial working memory, sustained attention and sensory gating (the brain's filtering of repeated sounds or signals). These improvements appeared stronger in patients who smoke, and the authors suggest this may help explain why schizophrenia and tobacco dependence so often occur together.

Mackowick KM, Barr MS, Wing VC et al. (2014). Neurocognitive endophenotypes in schizophrenia: modulation by nicotinic receptor systems. Prog Neuropsychopharmacol Biol Psychiatry. — PubMed PMID: 23871750 · doi:10.1016/j.pnpbp.2013.07.010

Nicotine facilitates memory consolidation in perceptual learning

Human trial, 2013. Researchers studied two groups of non-smoking men who learned a visual task in which they had to tell apart different textures on a screen. Right after training, one group chewed tobacco that contained nicotine for one hour, and the other group chewed a similar-tasting substance without nicotine. Brain-wave recordings showed differences in the nicotine group during that hour. When both groups were tested again the next day, both had improved, but the improvement was larger in the nicotine group, which the authors take as a sign that nicotine, acting on the brain's acetylcholine (nicotinic) receptors, helped lock in this kind of learning.

Beer AL, Vartak D, Greenlee MW (2013). Nicotine facilitates memory consolidation in perceptual learning. Neuropharmacology. — PubMed PMID: 22749926 · doi:10.1016/j.neuropharm.2012.06.019

Nicotine withdrawal modulates frontal brain function during an affective Stroop task

Human trial, 2012. Researchers scanned the brains of 17 nicotine-dependent smokers with functional MRI while they did a task that tested focus with upsetting or neutral pictures shown as distractions. Each person was scanned twice: once after 24 hours without smoking and once after smoking as usual. During withdrawal, parts of the front of the brain that handle self-control and attention worked harder during the task. The authors suggest the brain may need extra effort to stay focused during withdrawal, and that the low mood withdrawal brings may get in the way of focus when emotional distractions are present.

Froeliger B, Modlin L, Wang L et al. (2012). Nicotine withdrawal modulates frontal brain function during an affective Stroop task. Psychopharmacology (Berl). — PubMed PMID: 21989805 · doi:10.1007/s00213-011-2522-y

Nicotinic excitatory postsynaptic potentials in hippocampal CA1 interneurons are predominantly mediated by nicotinic receptors that contain α4 and β2 subunits

Cell study, 2011. This laboratory study looked at how the brain's own messenger acetylcholine activates nicotinic receptors on nerve cells in the hippocampus, a brain area involved in memory. The researchers used light-triggered release of acetylcholine and electrical recordings, and found that in a subgroup of inhibitory nerve cells the slow electrical responses came mainly from nicotinic receptors containing α4 and β2 subunits, the type also linked to memory, nicotine withdrawal, and decline in aging and Alzheimer's disease. These responses were largest in one layer of the hippocampus, which suggests the receptors may mainly affect signals arriving from outside the hippocampus. The results come from recordings of nerve cells in the lab, not from people.

Bell KA, Shim H, Chen CK et al. (2011). Nicotinic excitatory postsynaptic potentials in hippocampal CA1 interneurons are predominantly mediated by nicotinic receptors that contain α4 and β2 subunits. Neuropharmacology. — PubMed PMID: 21878344 · doi:10.1016/j.neuropharm.2011.08.024

Cognitive effects of nicotine: genetic moderators

Review, 2010. This review looks at how genes may shape the effects of nicotine on thinking and memory. The authors report that several studies found nicotine improves cognitive performance in both smokers and non-smokers, and that studies in mice lacking certain genes point to beta2 nicotinic receptors as essential for these effects, with alpha7 nicotinic receptors linked to attention and sensory filtering, especially in people with schizophrenia. Variations in dopamine D2 receptor, COMT enzyme and serotonin transporter genes appear to change how strongly people show thinking problems during smoking abstinence, or how much nicotine improves spatial working memory. The authors note that less is known about other dopamine-related genes, and they suggest that cognitive enhancement may contribute to nicotine's addictive actions.

Herman AI, Sofuoglu M (2010). Cognitive effects of nicotine: genetic moderators. Addict Biol. — PubMed PMID: 20456288 · doi:10.1111/j.1369-1600.2010.00213.x

Nicotine self-medication of cognitive-attentional processing

Review, 2009. This review looks at research on how nicotine affects thinking and attention, including how it works in the brain and which kinds of tests and study designs best show its effects. Most human studies have looked at how nicotine eases the thinking problems people have during withdrawal, and the authors say it is still debated whether nicotine directly improves thinking. The review discusses the idea that some smokers with thinking difficulties may use nicotine as a form of 'self-medication', which could make quitting harder for them. The authors call for more theory-driven research and for quit-smoking programs designed around this self-medication role in high-risk people.

Evans DE, Drobes DJ (2009). Nicotine self-medication of cognitive-attentional processing. Addict Biol. — PubMed PMID: 18855804 · doi:10.1111/j.1369-1600.2008.00130.x

Cognitive deficits in schizophrenia: focus on neuronal nicotinic acetylcholine receptors and smoking

Review, 2007. This review looks at the thinking problems people with schizophrenia often have, and at why so many of them smoke. It describes nicotinic acetylcholine receptors, the brain receptors that nicotine acts on. It covers how these receptors become less responsive after repeated stimulation and how the brain makes more of them, and how both changes may relate to schizophrenia. The authors look at whether smoking may help with these thinking problems. They also discuss drugs aimed at these receptors as possible future treatments for the thinking problems of schizophrenia.

Ochoa EL, Lasalde-Dominicci J (2007). Cognitive deficits in schizophrenia: focus on neuronal nicotinic acetylcholine receptors and smoking. Cell Mol Neurobiol. — PubMed PMID: 17554626 · doi:10.1007/s10571-007-9149-x

Nicotine-induced changes in neurotransmitter levels in brain areas associated with cognitive function

Animal study, 2004. Researchers gave male rats one injection of nicotine (0.5 mg/kg under the skin). They measured three brain messenger chemicals, dopamine, serotonin and norepinephrine, along with their breakdown products, in five brain areas involved in learning and memory. Nicotine raised dopamine in some of these areas and raised its breakdown products in all of them, and the dopamine changes lasted about 150 minutes. Serotonin and norepinephrine also rose, but for a shorter time. The authors conclude that a single dose of nicotine changes the release and turnover of these chemicals in brain areas linked to thinking and memory, but this was shown only in rats.

Singer S, Rossi S, Verzosa S et al. (2004). Nicotine-induced changes in neurotransmitter levels in brain areas associated with cognitive function. Neurochem Res. — PubMed PMID: 15453274 · doi:10.1023/b:nere.0000035814.45494.15

Smoking during pregnancy: a way to transfer the addiction to the next generation?

Review, 2002. This review looks at how smoking during pregnancy may affect children's brains and behavior later in life. It notes that studies of children whose mothers smoked while pregnant show higher risks of learning and thinking problems, attention deficit/hyperactivity disorder, conduct disorder, adult criminal behavior, and a greater tendency to start smoking and abuse alcohol. The authors explain that nicotine easily crosses the placenta, so the unborn baby is exposed to even higher nicotine levels than the mother. Because nicotinic receptors are already in the baby's brain in the first trimester and help guide brain development, the authors argue that nicotine may act directly on the developing brain for most of pregnancy.

Hellström-Lindahl E, Nordberg A (2002). Smoking during pregnancy: a way to transfer the addiction to the next generation?. Respiration. — PubMed PMID: 12169737 · doi:10.1159/000063261

Cognitive effects of nicotine

Review, 2001. This review looks at research on how nicotine and other substances that act on nicotinic receptors affect thinking skills. The authors report that nicotine has been found to improve performance on attention and memory tasks. They also report that clinical studies using nicotine skin patches showed benefits for thinking problems linked to Alzheimer's disease, schizophrenia and attention-deficit/hyperactivity disorder (ADHD). In animal studies, the improvement in working memory lasted with long-term exposure, and two types of nicotinic receptors in the hippocampus, a memory area of the brain, were found to be key to these effects.

Rezvani AH, Levin ED (2001). Cognitive effects of nicotine. Biol Psychiatry. — PubMed PMID: 11230877 · doi:10.1016/s0006-3223(00)01094-5

Nicotine and brain disorders

Review, 2000. This review looks at the nicotinic receptors in the brain, the docking sites that nicotine acts on. It explains that these receptors matter for memory and thinking, and that they play a part in several brain disorders: Parkinson's disease, Alzheimer's disease, Tourette's syndrome, schizophrenia, depression and attention deficit disorder. The authors write that clinical studies of these same conditions found nicotine had beneficial effects, both as a treatment and as a way to help prevent them. It is a summary of earlier research, not a new study, and the abstract gives no patient numbers.

Mihailescu S, Drucker-Colín R (2000). Nicotine and brain disorders. Acta Pharmacol Sin. — PubMed PMID: 11263271

Pharmacology of nicotine: addiction and therapeutics

Review, 1996. This review describes how nicotine works in the body, both as the substance that keeps people addicted to tobacco and as a medicine to help people quit smoking. Nicotine acts on nicotinic receptors in the nervous system, and its effects depend on how fast and by what route it is taken and on tolerance; a few people have been described who break down nicotine unusually slowly and make little cotinine. The authors note that nicotine affects most organ systems, but its contribution to smoking-related disease is still unclear. At the time, nicotine medicines were available as a gum, a skin patch and a nasal spray for quitting smoking, and nicotine was being studied for ulcerative colitis, Alzheimer's disease, Parkinson's disease, Tourette's syndrome, sleep apnea and attention deficit disorder.

Benowitz NL (1996). Pharmacology of nicotine: addiction and therapeutics. Annu Rev Pharmacol Toxicol. — PubMed PMID: 8725403 · doi:10.1146/annurev.pa.36.040196.003121

Nicotine as a cognitive enhancer

Review, 1992. This 1992 review looks at research on whether nicotine affects thinking skills. The authors report that in healthy volunteers, nicotine improved attention on many kinds of tasks and improved both short-term and longer-term memory. They also report that it improved attention in patients with probable Alzheimer's disease. Some of the memory effects may come from better attention, but others appear to come from the brain storing new memories more firmly, because nicotine still helped when it was given after the learning task.

Warburton DM (1992). Nicotine as a cognitive enhancer. Prog Neuropsychopharmacol Biol Psychiatry. — PubMed PMID: 1579636 · doi:10.1016/0278-5846(92)90069-q

Basic and clinical psychopharmacology of nicotine

Review, 1991. This review looks at how nicotine acts on the body, especially the brain, and what earlier studies found about its effects on thinking and performance in people. Studies have reported better attention, learning, reaction time and problem solving after nicotine, but the authors say most of these results are inconclusive because of problems with how the studies were designed. It is unclear whether the improvement after smoking comes from nicotine acting directly on the brain or from relief of withdrawal symptoms, and it is not known whether people become tolerant to these effects. The authors conclude that several mental processes are involved, not just arousal, and that nicotine's main effects may differ from person to person.

Le Houezec J, Benowitz NL (1991). Basic and clinical psychopharmacology of nicotine. Clin Chest Med. — PubMed PMID: 1747987

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PubMed Topic Searches

1. PubMed: Brain and Memory and nicotine (the search this page is built from)

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Connections

• Nicotine: The Research
• Dr. Bryan Ardis on this subject — his claims, presented on their own pages and kept separate from this research collection
• The Nicotine Patch, animated
• Nicotinic Acetylcholine Receptors
• Cigarette Smoke — what burnt tobacco adds that nicotine alone does not
• Mood and Mental Health
• Inflammation and Immunity
• Cancer Research
• Heart and Blood Vessels
• Metabolism and Weight
• Addiction and Withdrawal
• Patches, Gum and Delivery
• Toxicity and Safety

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