Nicotine, Mood and Mental Health

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1. The Papers
2. PubMed Topic Searches
3. Connections
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The Papers (24)

Newest first. Study types on this page — Human trial: 5 · Human observational study: 2 · Review: 8 · Animal study: 8 · Other: 1. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.

Foetal mouth movements: Effects of nicotine

Human observational study, 2021. Researchers used 4D ultrasound scans of unborn babies to see whether mouth movements differed between babies whose mothers did not smoke, smoked lightly, smoked heavily, or used an e-cigarette during pregnancy, with 106 scans at 32 weeks and 87 scans at 36 weeks of pregnancy. The study found no significant differences in how often the babies moved their mouths between the exposure groups at either time point. Mouth movements decreased from 32 to 36 weeks in babies of non-smokers and of e-cigarette users. The authors concluded that because babies' behaviour varies so much, mouth movements alone may not be a good way to compare groups, and several measures of behaviour together are needed to judge how cigarette and e-cigarette exposure affect a baby's developing nervous system.

Froggatt S, Reissland N, Covey J et al. (2021). Foetal mouth movements: Effects of nicotine. Acta Paediatr. — PubMed PMID: 34310742 · doi:10.1111/apa.16042

Nicotine inhibits the VTA-to-amygdala dopamine pathway to promote anxiety

Animal study, 2021. This study in mice looked at how nicotine acts on dopamine brain cells in a region called the ventral tegmental area. Injected nicotine switched on the dopamine cells that send signals to the brain's reward area (the nucleus accumbens), but switched off a separate group that sends signals to the amygdala, a region involved in fear and anxiety. The anxiety-like behavior came from nicotine acting on one type of nicotinic receptor (those containing the beta-2 subunit), and switching the amygdala-bound cells back on prevented nicotine's anxiety-causing effect. The authors suggest these two opposite responses may separately explain why nicotine is rewarding and why it causes anxiety, but the findings are in mice only.

Nguyen C, Mondoloni S, Le Borgne T et al. (2021). Nicotine inhibits the VTA-to-amygdala dopamine pathway to promote anxiety. Neuron. — PubMed PMID: 34242565 · doi:10.1016/j.neuron.2021.06.013

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

Nicotine Self-administration Is Not Increased in the Methylazoxymethanol Acetate Rodent Model of Schizophrenia

Animal study, 2020. People with schizophrenia smoke 4-5 times more often than the general population, and one idea is that they find nicotine more rewarding. This study tested that idea in rats treated to model schizophrenia, letting them give themselves nicotine at a range of doses, in both 1-hour and 23-hour sessions. The model rats and normal rats took the same amount of nicotine, though the model rats worked less for sugar or for rewarding visual signals. The authors conclude that, to the extent this rat model reflects the human disease, finding nicotine more rewarding does not explain the higher smoking rate in schizophrenia. These results come from rats only.

Weeks JJ, Rupprecht LE, Grace AA et al. (2020). Nicotine Self-administration Is Not Increased in the Methylazoxymethanol Acetate Rodent Model of Schizophrenia. Nicotine Tob Res. — PubMed PMID: 30899959 · doi:10.1093/ntr/ntz048

Nicotine effects on cognitive remediation training outcome in people with schizophrenia: A pilot study

Human trial, 2019. This small randomized trial enrolled 25 people with schizophrenia in a 10-week computer-based brain-training program to see whether nicotine taken before sessions would boost the benefits. Twice a week, one group took a nicotine lozenge before training and the other took a placebo lozenge. Overall thinking scores improved over time in both groups with no difference between them, but on reasoning and problem-solving the placebo group improved while the nicotine group did not, which the authors read as nicotine getting in the way of training gains. Neither group's psychiatric symptoms changed, both groups improved on quality-of-life and everyday-functioning measures, and the study found no evidence that nicotine made the training work better.

Hahn B, Shrieves ME, Yuille MB et al. (2019). Nicotine effects on cognitive remediation training outcome in people with schizophrenia: A pilot study. Psychiatry Res. — PubMed PMID: 31437659 · doi:10.1016/j.psychres.2019.112498

Alterations in NMDAR-mediated signaling within the laterodorsal tegmental nucleus are associated with prenatal nicotine exposure

Animal study, 2019. This animal study looked at how nicotine exposure before birth changes a brainstem area called the laterodorsal tegmental nucleus. This area helps control brain regions involved in reward, attention and behavior. After prenatal nicotine exposure, the researchers found changes in a type of glutamate receptor (the NMDA receptor). The changes went in opposite directions in large, likely acetylcholine-releasing nerve cells and in small, likely inhibitory nerve cells, and the small cells had more 'silent' connections. The authors suggest these changes could weaken this area's signals to its target brain regions and may help explain the behavioral problems linked to smoking during pregnancy. The results come from animals only.

Polli FS, Kohlmeier KA (2019). Alterations in NMDAR-mediated signaling within the laterodorsal tegmental nucleus are associated with prenatal nicotine exposure. Neuropharmacology. — PubMed PMID: 31437434 · doi:10.1016/j.neuropharm.2019.107744

Modeling nicotine regulation: A review of studies in smokers with mental health conditions

Review, 2018. This review looks at studies of smokers with mental health conditions who were switched to cigarettes with very low nicotine content. People with these conditions lose about 15 years of life compared with non-smokers without them, and two-thirds of that loss is put down to smoking. In randomized, double-blind studies, these smokers cut down how many cigarettes they smoked, with little or no effect on withdrawal, psychiatric symptoms or compensatory smoking. Some studies found that lowering nicotine worsened performance on thinking tests in smokers with schizophrenia, and giving nicotine replacement at the same time offset this.

Tidey JW, Davis DR, Miller ME et al. (2018). Modeling nicotine regulation: A review of studies in smokers with mental health conditions. Prev Med. — PubMed PMID: 30343684 · doi:10.1016/j.ypmed.2018.07.003

Prenatal Nicotine Exposure Impairs Executive Control Signals in Medial Prefrontal Cortex

Animal study, 2016. This study looked at rats whose mothers were given nicotine during pregnancy. The researchers recorded single brain cells in the medial prefrontal cortex, a front part of the brain involved in self-control, while the rats did a task that required them to stop a movement they had already started. The nicotine-exposed rats moved faster, made more early responses and were less able to stop on 'stop' trials. Their brain cells also carried weaker signals about response direction and about conflict between choices. The authors conclude that nicotine exposure before birth made the rats impulsive. This finding comes from rats only.

Bryden DW, Burton AC, Barnett BR et al. (2016). Prenatal Nicotine Exposure Impairs Executive Control Signals in Medial Prefrontal Cortex. Neuropsychopharmacology. — PubMed PMID: 26189451 · doi:10.1038/npp.2015.197

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

Chronic nicotine improves short-term memory selectively in a G72 mouse model of schizophrenia

Animal study, 2014. Researchers gave nicotine or salt water for a long period through small pumps placed under the skin. They tested two groups of mice: ordinary mice and mice genetically engineered to carry a gene linked to schizophrenia risk. In the engineered mice, long-term nicotine restored impaired sensory filtering, working memory and social recognition, but it made long-term spatial learning worse. In ordinary mice, nicotine disrupted thinking performance. The nicotine also changed the number of certain nicotine receptors in the brain, especially one receptor type in the hippocampus, a memory area; the authors suggest this may explain the effect, but these results come only from mice.

Hambsch B, Keyworth H, Lind J et al. (2014). Chronic nicotine improves short-term memory selectively in a G72 mouse model of schizophrenia. Br J Pharmacol. — PubMed PMID: 24417347 · doi:10.1111/bph.12578

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

Developmental nicotine exposure induced alterations in behavior and glutamate receptor function in hippocampus

Animal study, 2012. Researchers gave pregnant rats nicotine (6 mg/kg/day, infused under the skin) from the third day of pregnancy until birth, then studied the offspring. The young rats exposed to nicotine before birth showed more anxiety-like and depression-like behavior and had poorer spatial memory. In the hippocampus, a brain area important for memory, signaling between nerve cells and the strengthening of their connections (a process linked to learning) were reduced, along with lower levels of several proteins needed for glutamate signaling. These results come from rats only; the authors suggest that nicotine exposure from smoking during pregnancy could cause similar changes in the brain.

Parameshwaran K, Buabeid MA, Karuppagounder SS et al. (2012). Developmental nicotine exposure induced alterations in behavior and glutamate receptor function in hippocampus. Cell Mol Life Sci. — PubMed PMID: 22033836 · doi:10.1007/s00018-011-0805-4

Nicotine withdrawal symptoms in adolescent and adult twins

Human observational study, 2010. Researchers interviewed young people who smoke cigarettes by telephone: 3,112 adult twins in Australia aged 24 to 36 and 702 teenage and young adult twins in Missouri aged 15 to 21. They studied nicotine withdrawal symptoms and how much these depend on genes. About 44% met the criteria for nicotine withdrawal, with no difference between men and women or between age groups. More severe withdrawal was linked to more trouble quitting, heavier smoking, depression, anxiety, conduct problems and alcohol problems. Genes explained about 49% of the differences in withdrawal between people, and each person's own experiences and surroundings explained the other 51%.

Pergadia ML, Agrawal A, Heath AC et al. (2010). Nicotine withdrawal symptoms in adolescent and adult twins. Twin Res Hum Genet. — PubMed PMID: 20707706 · doi:10.1375/twin.13.4.359

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

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

A placebo-controlled trial of bupropion combined with nicotine patch for smoking cessation in schizophrenia

Human trial, 2008. This 10-week double-blind trial included 58 outpatient smokers with schizophrenia. Everyone wore a 21 mg/24 h nicotine patch, and each person also took either bupropion (300 mg/day) or a placebo pill. In the last 4 weeks of the trial, 8 of 29 people (27.6%) on bupropion plus the patch stopped smoking without a break, against 1 of 29 (3.4%) on placebo plus the patch. At 6 months, 4 of 29 (13.8%) versus 0 of 29 had not smoked in the past week, a difference that was not statistically significant. The combination was well tolerated, and neither bupropion nor quitting smoking significantly changed the symptoms of schizophrenia.

George TP, Vessicchio JC, Sacco KA et al. (2008). A placebo-controlled trial of bupropion combined with nicotine patch for smoking cessation in schizophrenia. Biol Psychiatry. — PubMed PMID: 18096137 · doi:10.1016/j.biopsych.2007.11.002

Effects of abstinence from tobacco: valid symptoms and time course

Review, 2007. This review updated a 1990 review on what happens when people stop using tobacco, looking at which symptoms are real signs of tobacco and nicotine withdrawal and how long they last. The author searched more than 3,500 studies published between 1990 and 2004 and used 120 of them, relying on their own judgment to select and interpret the data. Anger, anxiety, depression, difficulty concentrating, impatience, trouble sleeping and restlessness were judged to be real withdrawal symptoms; they peak within the first week and last 2-4 weeks. Constipation, cough, dizziness, more dreaming and mouth ulcers may also come from stopping, while drowsiness, fatigue and several other physical symptoms were judged not to be withdrawal effects.

Hughes JR (2007). Effects of abstinence from tobacco: valid symptoms and time course. Nicotine Tob Res. — PubMed PMID: 17365764 · doi:10.1080/14622200701188919

Hedonic capacity, cigarette craving, and diminished positive mood

Human trial, 2004. Researchers studied 35 smokers who went without nicotine for 48 hours. They wanted to know whether people with a lower capacity to feel pleasure have stronger urges to smoke during early nicotine withdrawal. Smokers with a lower capacity for pleasure had bigger increases in craving 24 hours after stopping. This happened because their positive mood dropped, not because their negative mood rose.

Cook JW, Spring B, McChargue D et al. (2004). Hedonic capacity, cigarette craving, and diminished positive mood. Nicotine Tob Res. — PubMed PMID: 14982686 · doi:10.1080/14622200310001656849

Cigarette-derived nicotine is not a medicine

Review, 2003. This review looks at whether the nicotine smokers get from cigarettes improves their mood. Smokers do feel calmer and less stressed when they smoke. The author argues that this is only short relief from the withdrawal symptoms that come back between cigarettes, not a real benefit. Studies that followed teenagers who started smoking found they reported more anxiety, stress and depression, and adults who quit reported lasting mood improvements. The review concludes there is no evidence that cigarettes provide medicinal benefits, and much evidence that nicotine dependency increases psychological distress in smokers, with stronger dependency linked to worse moods.

Parrott AC (2003). Cigarette-derived nicotine is not a medicine. World J Biol Psychiatry. — PubMed PMID: 12692774 · doi:10.3109/15622970309167951

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

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

Nicotinic receptor desensitization and sensory gating deficits in schizophrenia

Human trial, 1998. This small double-blind, placebo-controlled study included six people with schizophrenia. It tested whether nicotine receptors in the brain that become less responsive (desensitized) could explain a problem in how these patients filter out repeated sounds, measured with a brain-wave test called P50 gating. After a brief sleep, the patients' sound filtering returned to normal for a short time while they wore a placebo patch, but this improvement was reduced in all six patients while they wore a nicotine skin patch. The researchers concluded that receptor desensitization is responsible for the loss of this sound filtering in schizophrenia.

Griffith JM, O'Neill JE, Petty F et al. (1998). Nicotinic receptor desensitization and sensory gating deficits in schizophrenia. Biol Psychiatry. — PubMed PMID: 9646891 · doi:10.1016/s0006-3223(97)00362-4

Dramatic decreases in brain reward function during nicotine withdrawal

Animal study, 1998. This study in rats looked at what happens in the brain's reward system when animals that had been given nicotine for a long time suddenly stop getting it. During withdrawal, the rats' brain reward function dropped significantly, and this lasted for four days. Giving the rats on long-term nicotine a drug that blocks nicotinic receptors also lowered reward function, and larger doses had a bigger effect. The authors report that the size and length of this drop matched what is seen with other major addictive drugs, and they suggest it may help explain craving, relapse and continued tobacco use in people, though the findings come from animals only.

Epping-Jordan MP, Watkins SS, Koob GF et al. (1998). Dramatic decreases in brain reward function during nicotine withdrawal. Nature. — PubMed PMID: 9590692 · doi:10.1038/30001

Nicotine withdrawal versus other drug withdrawal syndromes: similarities and dissimilarities

Review, 1994. This review compares withdrawal from nicotine with withdrawal from other drugs. Many symptoms are shared, including anxiety, waking during sleep, depression, trouble concentrating, impatience, irritability or anger, and restlessness, while a slower heart rate and weight gain set tobacco withdrawal apart. Nicotine withdrawal may not cause medical problems, but it can last several weeks and be severe in some smokers. Like most drug withdrawals it is time-limited and eases with replacement therapy and gradual reduction, and the authors say it has not been established whether withdrawal plays a major role in going back to smoking.

Hughes JR, Higgins ST, Bickel WK (1994). Nicotine withdrawal versus other drug withdrawal syndromes: similarities and dissimilarities. Addiction. — PubMed PMID: 7841857 · doi:10.1111/j.1360-0443.1994.tb03744.x

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PubMed Topic Searches

1. PubMed: Mood and Mental Health and nicotine (the search this page is built from)

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Connections

• 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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