Nicotine, Mood and Mental Health

Table of Contents

1. Research at a Glance
2. The Papers
3. PubMed Topic Searches
4. More Nicotine Research
5. Connections
6. Featured Videos

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.

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The Papers (39)

Newest first. Study types on this page — Human trial: 5 · Human observational study: 3 · Review: 10 · Animal study: 20 · Other: 1. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.

Psychological distress, perceived psychological reward, and nicotine dependence among young people

Human observational study, 2026. This online survey studied young people in the United States, aged 14 to 25, who had recently started using e-cigarettes. It looked at how psychological distress (symptoms of anxiety and depression) related to nicotine dependence. It also asked whether the rewarding feelings people reported after vaping, such as feeling calmer, less irritable, more awake, better able to concentrate or less hungry, helped explain that link. Distress was directly linked to nicotine dependence, and part of the link ran through these rewarding feelings. Because everyone was surveyed only once, the authors say the results show associations, not cause and effect.

Figueroa W, Ferketich AK, Breitborde N et al. (2026). Psychological distress, perceived psychological reward, and nicotine dependence among young people. Drug Alcohol Depend. — PubMed PMID: 42826656 · doi:10.1016/j.drugalcdep.2026.113378

Tobacco Use Disorder and Co-Occurring Mental Health Conditions: Considerations for Future DSM

Review, 2026. This is a commentary, not a new study. It looks at how the psychiatric diagnostic manual (DSM) handles tobacco use disorder, which is dependence on tobacco and its nicotine, in people who also have mental health conditions. The authors note that these people smoke nearly 40% of the cigarettes smoked in the United States, and that nicotine withdrawal symptoms can look like anxiety, depression and bipolar disorder. They argue that the next edition of the manual should give more guidance on telling these conditions apart, on the causes they may share, and on routine screening and treatment for tobacco use as part of mental health care.

Kelly MM, Karekla M, Heffner JL (2026). Tobacco Use Disorder and Co-Occurring Mental Health Conditions: Considerations for Future DSM. J Nerv Ment Dis. — PubMed PMID: 42806843 · doi:10.1097/NMD.0000000000001877

Ionotropic Glutamate Receptor Function in Interpeduncular Nucleus Is Modulated by Nicotine Exposure

Animal study, 2025. This study in rats looked at a brain circuit (from the medial habenula to the interpeduncular nucleus) that is involved in mood, anxiety, and the unpleasant feelings of nicotine withdrawal. Researchers found specific glutamate receptors in this brain area and showed that in rats who had previously self-administered nicotine, these receptors responded less strongly to glutamate signaling. Applying nicotine directly to brain tissue from rats that had never been exposed to nicotine produced the same reduced response, suggesting nicotine itself can blunt this signaling pathway, which may contribute to the unpleasant feelings during nicotine withdrawal.

Yan Y, Tucker BR, Tapp AE et al. (2025). Ionotropic Glutamate Receptor Function in Interpeduncular Nucleus Is Modulated by Nicotine Exposure. eNeuro. — PubMed PMID: 41253496 · doi:10.1523/ENEURO.0052-25.2025

Kynurenine 3-monooxygenase deficiency induces depression-like behavior via enhanced antagonism of α7 nicotinic acetylcholine receptors by kynurenic acid

Animal study, 2021. In a mouse study, mice lacking the KMO enzyme built up a kynurenine pathway chemical called kynurenic acid in the brain's prefrontal cortex, and this was linked to depression-like behavior (more activity, less social interaction, and longer immobility in a swim test). These mice also had higher levels of a receptor nicotine normally acts on (the α7 nicotinic receptor). Giving nicotine blocked the increased activity, reduced social interaction, and prolonged immobility in these mice, though it did not change their sucrose preference. Blocking that same receptor reversed nicotine's effect on social interaction and immobility, showing nicotine's effect worked through that receptor.

Mori Y, Mouri A, Kunisawa K et al. (2021). Kynurenine 3-monooxygenase deficiency induces depression-like behavior via enhanced antagonism of α7 nicotinic acetylcholine receptors by kynurenic acid. Behav Brain Res. — PubMed PMID: 33607168 · doi:10.1016/j.bbr.2021.113191

Opposing effects of acute and repeated nicotine exposure on boldness in zebrafish

Animal study, 2020. Researchers gave zebrafish different doses and schedules of nicotine and measured 'boldness' by seeing how willing they were to approach a new object. A single dose of nicotine (short exposure to a high dose, or one hour of a low dose) made the fish bolder and more willing to explore. But after a low dose was repeated daily for 21 days, the fish became less bold. After repeated exposure stopped for two days (withdrawal), the fish also moved less.

Dean R, Duperreault E, Newton D et al. (2020). Opposing effects of acute and repeated nicotine exposure on boldness in zebrafish. Sci Rep. — PubMed PMID: 32444782 · doi:10.1038/s41598-020-65382-6

Fishing for a deeper understanding of nicotine effects using zebrafish behavioural models

Review, 2020. This review discusses using zebrafish as a model to study nicotine's behavioral effects, since long-term neurological effects and mechanisms of nicotine addiction are still not fully understood. It summarizes prior zebrafish research on how nicotine affects anxiety, learning and memory, addiction-related behavior, and social behaviors, and argues zebrafish offer a useful platform for studying nicotine's effects on the brain and for drug-addiction research.

Wronikowska O, Michalak A, Skalicka-Woźniak K et al. (2020). Fishing for a deeper understanding of nicotine effects using zebrafish behavioural models. Prog Neuropsychopharmacol Biol Psychiatry. — PubMed PMID: 31783041 · doi:10.1016/j.pnpbp.2019.109826

Cognitive rigidity and BDNF-mediated frontostriatal glutamate neuroadaptations during spontaneous nicotine withdrawal

Animal study, 2020. In mice given nicotine daily for 14 days and then withdrawn, researchers tested cognitive flexibility (the ability to switch strategies when rules changed). Mice withdrawing from nicotine needed more attempts to learn a new strategy and made more errors, with higher-dose mice making a distinct type of error unrelated to anxiety. Withdrawal also raised a brain growth factor (BDNF) in one brain region while lowering it in another, and changed how that factor affected brain signaling chemistry in different brain areas, suggesting these brain changes may underlie the thinking difficulties seen during withdrawal.

Cole RD, Zimmerman M, Matchanova A et al. (2020). Cognitive rigidity and BDNF-mediated frontostriatal glutamate neuroadaptations during spontaneous nicotine withdrawal. Neuropsychopharmacology. — PubMed PMID: 31752015 · doi:10.1038/s41386-019-0574-6

The modulatory role of nicotine on cognitive and non-cognitive functions

Review, 2019. This review looks at how nicotine affects thinking and other brain functions in both people and animals, including reward, addiction, learning and memory, anxiety, pain, body weight and body temperature. Nicotine works by switching on nicotinic acetylcholine receptors, which are found throughout the nervous system. The authors explain that the brain's dopamine reward system, along with areas such as the hippocampus and amygdala, carries many of these effects. They also describe how other brain chemical systems, including opioid, glutamate, cannabinoid, GABA, serotonin and nitric oxide signaling, help shape nicotine's effects.

Zarrindast MR, Khakpai F (2019). The modulatory role of nicotine on cognitive and non-cognitive functions. Brain Res. — PubMed PMID: 30529105 · doi:10.1016/j.brainres.2018.12.002

Nicotinic receptors mediate stress-nicotine detrimental interplay via dopamine cells' activity

Animal study, 2018. In mice, nicotine exposure increased sensitivity to stress, a key risk factor for mood disorders, by causing lasting changes in dopamine neurons. The effect depended on remodeling of nicotinic receptors: blocking one type of nicotinic receptor (beta2) prevented these stress-related brain changes from developing, blocking another type (alpha7) prevented them from being expressed as behavior, and deliberately activating alpha7 receptors in a specific brain region reproduced the harmful stress effects. The study identifies alpha7 nicotinic receptors as a possible target for future treatments of stress-related psychiatric conditions.

Morel C, Fernandez SP, Pantouli F et al. (2018). Nicotinic receptors mediate stress-nicotine detrimental interplay via dopamine cells' activity. Mol Psychiatry. — PubMed PMID: 29155800 · doi:10.1038/mp.2017.145

Reduction of anxiety sensitivity in relation to nicotine withdrawal symptoms during smoking cessation: an examination among successful quitters

Human observational study, 2018. Researchers followed 29 adult smokers who successfully quit and stayed abstinent, tracking how much their anxiety sensitivity changed and how their nicotine withdrawal symptoms progressed over the first two weeks of quitting. After accounting for factors like gender, treatment type, use of nicotine replacement therapy, nicotine dependence, alcohol problems, and starting anxiety levels, people whose anxiety sensitivity dropped more also saw their withdrawal symptoms fade faster. The authors suggest that targeting anxiety sensitivity directly might help manage withdrawal symptoms during a quit attempt.

Bakhshaie J, Zvolensky MJ, Langdon KJ et al. (2018). Reduction of anxiety sensitivity in relation to nicotine withdrawal symptoms during smoking cessation: an examination among successful quitters. Cogn Behav Ther. — PubMed PMID: 29130427 · doi:10.1080/16506073.2017.1395907

Nicotine-Derived Compounds as Therapeutic Tools Against Post-Traumatic Stress Disorder

Review, 2015. This review looks at cotinine, the main substance the body makes when it breaks down nicotine, as a possible treatment for post-traumatic stress disorder (PTSD). The authors note that in mouse models of PTSD, cotinine reduced anxiety-like and depression-like behavior and helped the mice unlearn fear responses, an effect that depended on a nicotine receptor in the brain called the alpha-7 nicotinic receptor. They describe how cotinine switches on signaling pathways linked to this receptor that support the brain's ability to rewire itself. The authors put forward the idea that cotinine might ease PTSD symptoms in this way, but the evidence they describe comes from animal studies, not from people.

Barreto GE, Yarkov A, Avila-Rodriguez M et al. (2015). Nicotine-Derived Compounds as Therapeutic Tools Against Post-Traumatic Stress Disorder. Curr Pharm Des. — PubMed PMID: 26166610 · doi:10.2174/1381612821666150710145250

Anxiogenic-like effects of chronic nicotine exposure in zebrafish

Animal study, 2015. Adult zebrafish were exposed to nicotine in their water (1-2 mg/L) for 4 days. This chronic exposure slightly increased shoaling behavior (fish grouping together) but did not change baseline cortisol levels. The fish also showed strong anxiety-like behavior in a standard tank-based behavioral test, a pattern the researchers say generally matches what has been seen with chronic nicotine in clinical and rodent studies.

Stewart AM, Grossman L, Collier AD et al. (2015). Anxiogenic-like effects of chronic nicotine exposure in zebrafish. Pharmacol Biochem Behav. — PubMed PMID: 25643654 · doi:10.1016/j.pbb.2015.01.016

Differential associations between components of anxiety sensitivity and smoking-related characteristics

Human observational study, 2015. This study surveyed 314 adult smokers (32% female, average age 44) who smoked at least 10 cigarettes a day, looking at how different types of anxiety sensitivity relate to smoking habits. People who feared the mental effects of anxiety had more trouble staying smoke-free and expected smoking to relieve negative feelings and withdrawal; those who feared social judgment expected smoking to bring positive feelings; and those who feared physical anxiety symptoms reported stronger withdrawal symptoms during past quit attempts.

Guillot CR, Zvolensky MJ, Leventhal AM (2015). Differential associations between components of anxiety sensitivity and smoking-related characteristics. Addict Behav. — PubMed PMID: 25218070 · doi:10.1016/j.addbeh.2014.08.004

Acute nicotine delays extinction of contextual fear in mice

Animal study, 2014. Mice were trained to fear a specific environment through a mild foot-shock paired with sound, then given either a single nicotine dose or saline before being re-exposed to that environment without the shock, a process that normally lets fear fade over time. Mice given nicotine took longer for their fear response (freezing in place) to fade when back in the context where the shock happened, compared to mice given saline. Nicotine had no effect on fear tied to the sound cue itself or to freezing in a brand-new, unfamiliar environment.

Kutlu MG, Gould TJ (2014). Acute nicotine delays extinction of contextual fear in mice. Behav Brain Res. — PubMed PMID: 24487010 · doi:10.1016/j.bbr.2014.01.031

Repeated transcranial direct current stimulation prevents abnormal behaviors associated with abstinence from chronic nicotine consumption

Animal study, 2014. Mice were given repeated brain stimulation (tDCS) over five days. In mice not exposed to nicotine, the stimulation had antidepressant-like effects, improved working memory, and reduced the animals' preference for nicotine. In mice that had been chronically given nicotine, the same stimulation reversed depression-like behavior and the nicotine-seeking behavior that abstinence caused.

Pedron S, Monnin J, Haffen E et al. (2014). Repeated transcranial direct current stimulation prevents abnormal behaviors associated with abstinence from chronic nicotine consumption. Neuropsychopharmacology. — PubMed PMID: 24154668 · doi:10.1038/npp.2013.298

Cognition as a therapeutic target in late-life depression: potential for nicotinic therapeutics

Review, 2013. This review looks at late-life depression, which affects both mood and thinking in older adults. The authors note that antidepressants help some patients but often do not bring thinking skills back to the level of older adults without depression. They propose a treatment model that uses nicotinic stimulation alongside antidepressant treatment, to improve thinking and possibly make the antidepressant work better. They say some drugs that act on specific nicotinic receptors have improved thinking in earlier studies, but little is known about their effect in depressed older patients, so this model is a proposal that has not been tested.

Zurkovsky L, Taylor WD, Newhouse PA (2013). Cognition as a therapeutic target in late-life depression: potential for nicotinic therapeutics. Biochem Pharmacol. — PubMed PMID: 23933385 · doi:10.1016/j.bcp.2013.07.032

Involvement of rat dopaminergic system of nucleus accumbens in nicotine-induced anxiogenic-like behaviors

Animal study, 2012. Male rats had nicotine injected directly into a brain region called the central amygdala, and researchers tested anxiety-like behavior using a maze with open and closed arms. This nicotine injection reduced the time rats spent in the open arms, suggesting an anxiety-increasing effect. The study found this effect involved dopamine D1 and D2 receptors in a nearby brain region (the nucleus accumbens shell), since blocking dopamine signaling there with specific drugs reduced the anxiety-like behavior caused by nicotine.

Zarrindast MR, Khalifeh S, Rezayof A et al. (2012). Involvement of rat dopaminergic system of nucleus accumbens in nicotine-induced anxiogenic-like behaviors. Brain Res. — PubMed PMID: 22595749 · doi:10.1016/j.brainres.2012.04.036

Brain regions mediating α3β4 nicotinic antagonist effects of 18-MC on nicotine self-administration

Animal study, 2011. Rats that could self-administer nicotine were given a drug called 18-MC, which blocks a specific type of nicotine receptor (alpha3beta4), either throughout the body or injected directly into particular brain regions. Putting 18-MC into the medial habenula, the basolateral amygdala, or the dorsolateral tegmentum reduced how much nicotine the rats gave themselves, while putting it into the interpeduncular nucleus actually increased nicotine self-administration, and injecting it into the ventral tegmental area had no effect. The results suggest 18-MC lowers nicotine-seeking behavior in rats by acting on nicotine receptors in some brain areas, while a different brain area may be involved in reducing unpleasant or low-mood effects of nicotine withdrawal.

Glick SD, Sell EM, McCallum SE et al. (2011). Brain regions mediating α3β4 nicotinic antagonist effects of 18-MC on nicotine self-administration. Eur J Pharmacol. — PubMed PMID: 21871879 · doi:10.1016/j.ejphar.2011.08.001

Effects of serotonin (5-HT)2 receptor ligands on depression-like behavior during nicotine withdrawal

Animal study, 2010. Researchers studied rats to see whether drugs that act on serotonin 2 receptors could ease depression-like behavior during nicotine withdrawal, measured by how long the rats stayed still in a swimming test. After 5 days of nicotine, rats withdrawn from it stayed still for longer, with the effect at its strongest on day 3 of withdrawal. A drug that blocks the 5-HT2A receptor, drugs that activate the 5-HT2C receptor, and the antidepressant imipramine all shortened this time in the withdrawn rats. One of the drugs may have worked only by making the rats more active in general. These results are only in rats, and the authors suggest such drugs be studied as add-ons to help people quitting smoking with depressed mood.

Zaniewska M, McCreary AC, Wydra K et al. (2010). Effects of serotonin (5-HT)2 receptor ligands on depression-like behavior during nicotine withdrawal. Neuropharmacology. — PubMed PMID: 20153341 · doi:10.1016/j.neuropharm.2010.02.006

Nicotine and extinction of fear conditioning

Animal study, 2010. Mice were trained to fear a sound paired with a mild foot shock, then went through sessions meant to extinguish that fear, with nicotine or saline given before training and/or extinction. Giving nicotine just before extinction sessions helped the fear memory fade faster, including blocking the fear from coming back when mice were moved to a different setting. But giving nicotine during both the original fear training and the extinction sessions had the opposite effect, making the fear harder to extinguish and, in the different-setting test, making the fear more likely to return.

Elias GA, Gulick D, Wilkinson DS et al. (2010). Nicotine and extinction of fear conditioning. Neuroscience. — PubMed PMID: 19931599 · doi:10.1016/j.neuroscience.2009.11.022

Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications

Other, 2009. This is a hypothesis paper, not a new study, about why people with schizophrenia smoke more than people with other serious mental illnesses. The author draws on earlier research suggesting that people with schizophrenia have weak natural signaling through nicotinic receptors in the brain. This disrupts 'sensory gating', the brain's filtering of incoming information, and the author argues that smoking is an attempt to self-medicate this problem with nicotine. The author proposes that nicotine may ease positive symptoms and might ultimately help prevent negative symptoms, and suggests that nicotine delivered in a less toxic form than cigarettes should be studied as a treatment, while noting that smoking harms physical health.

Conway JL (2009). Exogenous nicotine normalises sensory gating in schizophrenia; therapeutic implications. Med Hypotheses. — PubMed PMID: 19328631 · doi:10.1016/j.mehy.2009.02.017

Nicotine (NC)-induced "depressive" behavioral symptoms and effects of antidepressants including cannabinoids (CBs)

Animal study, 2008. This study in mice tested whether repeated nicotine injections (0.3 mg/kg for 4 days) cause depression-like behavior, compared with a standard stress model of being held still for 10 minutes a day. Nicotine increased depression-like behavior in two standard behavioral tests, lasting up to 1 day in one test but only 2 hours in the other. Three antidepressant drugs and two compounds that act on the body's cannabinoid system reduced these behaviors in the first test, but only the two cannabinoid-acting compounds reduced them in the second test. The authors say the results support a risk from repeated nicotine use, and they are from mice only.

Hayase T (2008). Nicotine (NC)-induced "depressive" behavioral symptoms and effects of antidepressants including cannabinoids (CBs). J Toxicol Sci. — PubMed PMID: 19043277 · doi:10.2131/jts.33.555

Spontaneous nicotine withdrawal potentiates the effects of stress in rats

Animal study, 2008. Rats were given nicotine continuously through implanted pumps for several days, then had the nicotine stopped. The rats did not become more easily startled under normal conditions, but when a bright light was used as a stressor, nicotine withdrawal made their startle response to that stressful light much stronger. Using drugs that block nicotine's receptors to trigger withdrawal right away, instead of letting it happen naturally, did not produce this effect. The findings suggest nicotine withdrawal makes animals more reactive to stress rather than causing anxiety on its own.

Jonkman S, Risbrough VB, Geyer MA et al. (2008). Spontaneous nicotine withdrawal potentiates the effects of stress in rats. Neuropsychopharmacology. — PubMed PMID: 18033237 · doi:10.1038/sj.npp.1301607

The possible contribution of neuronal nicotinic acetylcholine receptors in depression

Review, 2005. This review article discusses how nicotine acts on nicotinic acetylcholine receptors in the brain and examines the long-observed link between smoking and psychiatric conditions, including the finding that quitting smoking is followed by a higher chance of major depression. The authors discuss possible ways nicotine's effects on brain receptors could either worsen or help protect against mood disorders, and raise the idea of new depression treatments based on this receptor system. This is a discussion/review piece rather than a new experiment, so no original data on humans, animals, or cells is reported.

Bertrand D (2005). The possible contribution of neuronal nicotinic acetylcholine receptors in depression. Dialogues Clin Neurosci. — PubMed PMID: 16156379 · doi:10.31887/DCNS.2005.7.3/dbertrand

Novelty reward as a measure of anhedonia

Animal study, 2005. This review discusses research on rats measuring anhedonia (reduced sensitivity to pleasure) using a novel-object place-conditioning test. It reports that withdrawal from chronic nicotine blocked the rats' preference for places associated with novel objects, and this effect was not explained by changes in object interaction, general activity, novelty detection, or learning ability. The authors conclude that nicotine withdrawal directly reduced the rewarding value of novelty in these animals.

Bevins RA, Besheer J (2005). Novelty reward as a measure of anhedonia. Neurosci Biobehav Rev. — PubMed PMID: 15876456 · doi:10.1016/j.neubiorev.2005.03.013

Nicotine treatment of obsessive-compulsive disorder

Human trial, 2004. A patient with obsessive-compulsive disorder (OCD) appeared to improve markedly while using nicotine on their own, so the researchers gave nicotine to four more people with OCD for eight weeks. Everyone knew they were getting nicotine, and there was no comparison group. Four of the five patients improved on the standard OCD symptom scale, and for these four, nicotine chewing gum helped them cope better in stressful situations that usually set off their OCD. Because the study was so small, the authors said a larger, controlled study is needed.

Lundberg S, Carlsson A, Norfeldt P et al. (2004). Nicotine treatment of obsessive-compulsive disorder. Prog Neuropsychopharmacol Biol Psychiatry. — PubMed PMID: 15610934 · doi:10.1016/j.pnpbp.2004.06.014

Smoking and depression

Review, 2004. This review article discusses the two-way relationship between smoking and depression, focusing on nicotine's effects on brain biology as they relate to depression. It notes genetic factors may account for up to 67% of smoking initiation, maintenance and dependence, and that nicotine withdrawal can mimic or trigger depression symptoms.

Paperwalla KN, Levin TT, Weiner J et al. (2004). Smoking and depression. Med Clin North Am. — PubMed PMID: 15464109 · doi:10.1016/j.mcna.2004.06.007

Behavioral and neurochemical vulnerability during adolescence in mice: studies with nicotine

Animal study, 2004. Researchers gave mice access to nicotine in their drinking water during different stages of adolescence, then tested their anxiety and activity levels. Mice that drank nicotine during the middle of adolescence showed changed exploration and anxiety behavior at the time, and two months later their movement patterns in a new environment were disrupted. In a second experiment, nicotine injections had opposite effects on anxiety in adolescent versus adult mice, and in adolescent mice nicotine exposure reduced certain glutamate receptor subunits (AMPA GluR2/3) in brain regions involved in addiction, an effect not seen the same way in adult mice.

Adriani W, Granstrem O, Macri S et al. (2004). Behavioral and neurochemical vulnerability during adolescence in mice: studies with nicotine. Neuropsychopharmacology. — PubMed PMID: 14666123 · doi:10.1038/sj.npp.1300366

Common factors across acute subjective effects of nicotine

Human trial, 2003. Researchers gave 93 people, including current smokers, former smokers and people who had never smoked, nicotine by nasal spray at three doses (0, 10 and 20 micrograms per kilogram of body weight). Each person rated how they felt on 23 scales and on a standard mood questionnaire. The many different feelings clustered into five groups: a 'head rush' (buzzed, lightheaded, jittery), positive mood (comfortable, satisfied, relaxed), negative mood (anger, depression, tension), tiredness and feeling energized. These five groups appeared in smokers and non-smokers alike, but the groups differed in how strongly they felt the head rush, the positive mood and the energy, which the authors suggest may reflect tolerance to nicotine.

Perkins KA, Jetton C, Keenan J (2003). Common factors across acute subjective effects of nicotine. Nicotine Tob Res. — PubMed PMID: 14668070 · doi:10.1080/14622200310001614629

Prolonged nicotine patch use in quitters with past abstinence-induced depressed mood

Human trial, 2003. This randomized trial included 55 smokers who had felt depressed in earlier attempts to quit. After an initial high-dose nicotine patch phase, one group stayed on a 21 mg nicotine patch for 8 more weeks and the other group followed the usual schedule of tapering the dose down. The group that stayed on the full dose reported less craving, but withdrawal symptoms did not differ, and neither did continuous abstinence or relapse rates. The full-dose group had lower relapse rates only when people who dropped out without relapsing were counted as successes, and the authors suggest any benefit of staying on the full dose may last only as long as the dosing continues.

Pomerleau OF, Pomerleau CS, Marks JL et al. (2003). Prolonged nicotine patch use in quitters with past abstinence-induced depressed mood. J Subst Abuse Treat. — PubMed PMID: 12646326 · doi:10.1016/s0740-5472(02)00320-3

Conditioned anxiety to nicotine

Animal study, 2002. This study in rats tested whether the anxiety caused by a single high dose of nicotine could become linked to the place and situation where the rats experienced it. Rats given nicotine 5 minutes before a social test spent less time interacting with other rats, which the researchers read as a sign of anxiety. A day later, without any nicotine, only rats that had taken the social test after a nicotine injection still showed this anxiety. The anxiety was tied to that specific test and did not carry over to a different anxiety test. Four days of earlier nicotine injections did not stop this learned anxiety from developing, but four weeks of the rats giving themselves nicotine did stop it.

File SE, Cheeta S, Irvine EE et al. (2002). Conditioned anxiety to nicotine. Psychopharmacology (Berl). — PubMed PMID: 12424555 · doi:10.1007/s00213-002-1219-7

Different treatment regimens and the development of tolerance to nicotine's anxiogenic effects

Animal study, 2001. Rats were given nicotine daily by IV injection, under-the-skin injection, or a continuous pump, and tested in a social interaction test used to measure anxiety. After 4 days, nicotine reduced social interaction in all groups, suggesting an anxiety-like effect, while activity levels stayed normal. This anxiety-like effect was still present but milder after 4 weeks, showing the rats built up partial tolerance regardless of which delivery method was used, and peak nicotine blood levels differed a lot between methods without changing how fast tolerance developed. No differences in social interaction appeared when rats were tested drug-free 24 and 72 hours after stopping nicotine.

Irvine EE, Cheeta S, Marshall M et al. (2001). Different treatment regimens and the development of tolerance to nicotine's anxiogenic effects. Pharmacol Biochem Behav. — PubMed PMID: 11526975 · doi:10.1016/s0091-3057(01)00469-5

Tolerance to midazolam's anxiolytic effects after short-term nicotine treatment

Animal study, 2001. Rats were given low-dose nicotine injections for 6 days, then tested with midazolam (an anti-anxiety drug) injected directly into two brain regions. Normally midazolam reduced anxious behavior in a social test, but after the nicotine pre-treatment this calming effect was lost, developing faster than the tolerance that builds up with repeated benzodiazepine use alone. The nicotine treatment also reduced benzodiazepine receptor binding in the hippocampus, which may explain the tolerance in that brain region, while other mechanisms involving serotonin may be at play in a second region.

Irvine EE, Cheeta S, Lovelock C et al. (2001). Tolerance to midazolam's anxiolytic effects after short-term nicotine treatment. Neuropharmacology. — PubMed PMID: 11311899 · doi:10.1016/s0028-3908(00)00211-2

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

Nicotine patch and paroxetine for smoking cessation

Human trial, 2000. 224 smokers trying to quit were randomly assigned to a nicotine patch plus either a placebo pill, 20 mg paroxetine, or 40 mg paroxetine for 8-9 weeks. Quit rates at 4, 10, and 26 weeks were not significantly different between the three groups overall, but the combined patch-plus-paroxetine treatment reduced craving and depression symptoms more than the patch alone. Among people who actually took their medication as prescribed, those on paroxetine had notably higher quit rates at 4 weeks than those on placebo.

Killen JD, Fortmann SP, Schatzberg AF et al. (2000). Nicotine patch and paroxetine for smoking cessation. J Consult Clin Psychol. — PubMed PMID: 11068974

Nicotine addiction

Review, 1999. This review article describes nicotine as the substance that keeps people addicted to tobacco. Nicotine works on nicotinic receptors in the nervous system. These receptors come in many different types and locations, which accounts for the many effects tobacco users experience. The authors report that nicotine addiction is more common and more severe in people with a history of major depression, schizophrenia, or alcohol or other drug problems. They note that a cigarette delivers nicotine to the brain quickly and in fairly high amounts, which makes repeated use more likely. Addiction severity can be measured with standard questionnaires, but these predict poorly how hard it will be for a person to stop using tobacco.

Benowitz NL (1999). Nicotine addiction. Prim Care. — PubMed PMID: 10436290 · doi:10.1016/s0095-4543(05)70120-2

Antidepressant effects of nicotine in an animal model of depression

Animal study, 1999. This study used a rat strain bred as a model of depression (Flinders Sensitive Line rats) and compared it with a control strain. The rats received nicotine (0.4 mg/kg by injection under the skin) either once or daily for 14 days. Nicotine improved the depression-model rats' performance on a forced swim test, a common animal test of depression-like behavior, but did not change the control rats' performance, and this effect was separate from any change in how much the rats moved around. The depression-model rats also had more of one type of nicotinic receptor (alpha4beta2) in several brain areas, which the authors say points to these receptors playing a role in depression-like traits; these results come from rats only.

Tizabi Y, Overstreet DH, Rezvani AH et al. (1999). Antidepressant effects of nicotine in an animal model of depression. Psychopharmacology (Berl). — PubMed PMID: 10102772 · doi:10.1007/s002130050879

Nicotine: abused substance and therapeutic agent

Review, 1998. This is a review discussing nicotine, the main addictive chemical in tobacco. It describes how nicotine can affect mood and thinking in ways that help explain why smokers keep smoking, though the paper notes effects on mood have been reported to go both ways. It also discusses epidemiological and experimental findings suggesting smoking, nicotine, or both might protect against certain diseases, and raises the idea that nicotine or related compounds might someday be used as a treatment to study how the brain works.

Le Houezec J (1998). Nicotine: abused substance and therapeutic agent. J Psychiatry Neurosci. — PubMed PMID: 9549250

Nicotine effects on adults with attention-deficit/hyperactivity disorder

Human trial, 1996. This was a double-blind, placebo-controlled study of nicotine skin patches in 17 adults with ADHD (6 smokers, 11 nonsmokers). A single dose of nicotine improved overall clinical ratings and vigor, and it sped up and steadied reaction time on an attention test; it also improved accuracy on a time-estimation task. Because the benefits showed up in nonsmokers too, the researchers concluded the effects were not simply relief from nicotine withdrawal, and they called for further clinical trials of nicotine in ADHD.

Levin ED, Conners CK, Sparrow E et al. (1996). Nicotine effects on adults with attention-deficit/hyperactivity disorder. Psychopharmacology (Berl). — PubMed PMID: 8741955 · doi:10.1007/BF02246281

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Connections

• Serotonin, Mood & SSRIs — interactive animation
• Nicotine: The Research
• The Nicotine Patch, animated
• Nicotinic Acetylcholine Receptors
• Cigarette Smoke — what burnt tobacco adds that nicotine alone does not
• Brain and Memory
• 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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