Nicotine, the Brain and Memory
Nicotine acts on the nicotinic acetylcholine receptors that the brain uses for attention and memory, and those receptors are among the first to be lost in Alzheimer's and Parkinson's disease. This page collects the published research on nicotine and cognition, neuroprotection and neurodegenerative disease, from cell studies to human trials, each summarised in plain language with its PubMed record.
This collection is research only: papers found on PubMed, each described as its own abstract reports it. Cell and animal results are labelled as such, and harms are listed beside benefits. It is not medical advice.
Table of Contents
Research at a Glance
What kind of study each paper on this page is, and when the papers were published. Hover over a bar for its count.
The Papers (25)
Newest first. Study types on this page — Human trial: 2 · Review: 15 · Animal study: 8. 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
Acute administration of nicotine does not enhance cognitive functions
Human trial, 2019. Researchers tested whether smoking one cigarette with a nicotine yield of 0.5 mg changes thinking skills in 22 young occasional smokers aged 19 to 29. Each person did tests of attention, working memory and visual-spatial reasoning on two days, two days apart: once before and after smoking a cigarette, and once before and after drinking a glass of water instead. The cigarette had no significant effect on reaction time or accuracy in any of the three areas. The authors say that, at least in young occasional smokers, smoking does not affect thinking, and that smokers' belief that it helps them concentrate is probably a kind of thinking bias.
Grus A, Hromatko I (2019). Acute administration of nicotine does not enhance cognitive functions. Arh Hig Rada Toksikol. — PubMed PMID: 32623864 · doi:10.2478/aiht-2019-70-3257
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
Neuroprotective Effects of Nicotine on Hippocampal Long-Term Potentiation in Brain Disorders
Review, 2018. This review looks at long-term potentiation, a strengthening of connections between brain cells in the hippocampus that is thought to underlie learning and memory. Both its early phase (linked to short-term memory) and its late phase (linked to long-term memory) can be badly reduced in conditions that impair learning and memory. The authors summarize research in which treatment with nicotine restored these reduced forms of long-term potentiation. The abstract does not say whether the studies reviewed were done in animals or in people.
Alkadhi KA (2018). Neuroprotective Effects of Nicotine on Hippocampal Long-Term Potentiation in Brain Disorders. J Pharmacol Exp Ther. — PubMed PMID: 29914875 · doi:10.1124/jpet.118.247841
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
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
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
Heterogeneity across brain regions and neurotransmitter interactions with nicotinic effects on memory function
Review, 2015. This review looks at how the brain's nicotinic receptors, which nicotine acts on, help with memory, and how their role differs between brain areas. In rats, blocking two of the main nicotinic receptor types in memory areas such as the hippocampus, the amygdala and part of the thalamus impaired memory in a maze task, while drugs that activate these receptors improved learning, memory and attention. Blocking both receptor types together did not make the memory loss worse than blocking one alone. The authors also describe a large loss of these receptors in the hippocampus in Alzheimer's disease and abnormal receptor levels in schizophrenia. They note that long-term nicotine exposure, such as from tobacco use, increases the number of these receptors, and that it is still unclear whether activating or desensitizing the receptors is what improves thinking.
Levin ED, Hall BJ, Rezvani AH (2015). Heterogeneity across brain regions and neurotransmitter interactions with nicotinic effects on memory function. Curr Top Behav Neurosci. — PubMed PMID: 25655888 · doi:10.1007/978-3-319-13665-3_4
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
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 exposure during adolescence leads to short- and long-term changes in spike timing-dependent plasticity in rat prefrontal cortex
Animal study, 2012. Researchers gave rats nicotine injections three times a day for 10 days, either in adolescence or in adulthood, and then measured a form of learning-related strengthening of connections between nerve cells (synaptic plasticity) in the prefrontal cortex, a brain area involved in attention and thinking. During and right after nicotine exposure in adolescence, this strengthening was strongly reduced. Five weeks after adolescent exposure it was increased instead, a change not seen in rats given nicotine as adults. The researchers linked these short- and long-term changes to altered signaling through a receptor called mGluR2, and they suggest these changes may explain the attention and thinking problems seen later in life after adolescent nicotine exposure. These results come from rats only.
Goriounova NA, Mansvelder HD (2012). Nicotine exposure during adolescence leads to short- and long-term changes in spike timing-dependent plasticity in rat prefrontal cortex. J Neurosci. — PubMed PMID: 22855798 · doi:10.1523/JNEUROSCI.5502-11.2012
Prenatal nicotine exposure mouse model showing hyperactivity, reduced cingulate cortex volume, reduced dopamine turnover, and responsiveness to oral methylphenidate treatment
Animal study, 2012. Researchers exposed mice to nicotine before birth and then studied their offspring. Both male and female offspring were hyperactive, mostly during their active dark phase. They also had a smaller cingulate cortex, a brain area involved in attention, and lower dopamine turnover in the frontal cortex. A single oral dose of methylphenidate (0.75 mg/kg), an ADHD medicine, reduced the hyperactivity and raised frontal-cortex dopamine turnover; the same drug given by injection did not. The authors say this mouse model closely resembles ADHD in people, but these results come from mice only.
Zhu J, Zhang X, Xu Y et al. (2012). Prenatal nicotine exposure mouse model showing hyperactivity, reduced cingulate cortex volume, reduced dopamine turnover, and responsiveness to oral methylphenidate treatment. J Neurosci. — PubMed PMID: 22764249 · doi:10.1523/JNEUROSCI.1041-12.2012
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
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
Prenatal nicotine exposure evokes alterations of cell structure in hippocampus and somatosensory cortex
Animal study, 2002. Researchers gave pregnant rats nicotine throughout pregnancy at 2 mg/kg/day, a dose that produces blood nicotine levels similar to those in smokers. They then examined the brains of the young and adolescent offspring. In the hippocampus, a memory centre, brain cells were much smaller, cell layers were thinner and cells were packed more densely. In the sensory cortex there were fewer medium-sized nerve cells and more small cells, and all regions examined had more support (glial) cells. The authors conclude that nicotine exposure before birth disrupts brain cell development and leaves lasting changes in brain regions involved in learning and memory. This result is in rats only.
Roy TS, Seidler FJ, Slotkin TA (2002). Prenatal nicotine exposure evokes alterations of cell structure in hippocampus and somatosensory cortex. J Pharmacol Exp Ther. — PubMed PMID: 11752107 · doi:10.1124/jpet.300.1.124
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
Are the cognitive-enhancing effects of nicotine in the rat with lesions to the forebrain cholinergic projection system mediated by an interaction with the noradrenergic system?
Animal study, 1994. Rats had parts of their brain's acetylcholine or noradrenaline pathways damaged to study memory. Nicotine improved performance on a working-memory maze task in rats with the acetylcholine-pathway damage, but had no effect on a separate reference-memory task. The researchers concluded this memory-boosting effect of nicotine was not due to an interaction with the noradrenaline pathway.
Grigoryan GA, Mitchell SN, Hodges H et al. (1994). Are the cognitive-enhancing effects of nicotine in the rat with lesions to the forebrain cholinergic projection system mediated by an interaction with the noradrenergic system?. Pharmacol Biochem Behav. — PubMed PMID: 7862702 · doi:10.1016/0091-3057(94)90063-9
Scopolamine reversal of nicotine enhanced delayed matching-to-sample performance in monkeys
Animal study, 1993. Five adult monkeys trained on a memory task (delayed matching-to-sample) were given nicotine injections, which improved their performance on the task in a dose-dependent way, and the best dose also helped performance a day later without more nicotine. When the monkeys were pretreated with scopolamine, a drug that blocks acetylcholine receptors, at a low dose, it completely blocked nicotine's memory-boosting effect. The researchers concluded this supports the idea that nicotine's memory benefit works by triggering acetylcholine release and stimulating muscarinic receptors in the brain.
Terry AV, Buccafusco JJ, Jackson WJ (1993). Scopolamine reversal of nicotine enhanced delayed matching-to-sample performance in monkeys. Pharmacol Biochem Behav. — PubMed PMID: 8415832 · doi:10.1016/0091-3057(93)90141-f
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
Nicotine enhances delayed matching-to-sample performance by primates
Animal study, 1988. Researchers gave nicotine to five young adult macaque monkeys trained on a memory task in which they had to remember and match an image after delays of up to 60 seconds. Nicotine reliably improved their performance, by an average of 10% at the longest delay, where remembering was hardest. The benefit disappeared when a drug that blocks nicotinic receptors in the brain was given first, but not when receptors outside the brain were blocked, which suggests the effect works through brain receptors. These results are in monkeys only; a high dose of the brain-receptor blocker on its own clearly worsened memory performance.
Elrod K, Buccafusco JJ, Jackson WJ (1988). Nicotine enhances delayed matching-to-sample performance by primates. Life Sci. — PubMed PMID: 2899825 · doi:10.1016/0024-3205(88)90318-9
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More Nicotine Research
All nicotine research →Every page in the collection, with how many papers each one lists.
Connections
- How Memories Form: Synaptic Plasticity (LTP) — interactive animation
- 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