Nicotine and Multiple Sclerosis: The Research

Smoking raises the risk of multiple sclerosis while Scandinavian snus users show lower risk, which points away from nicotine and toward smoke, and animal studies of nicotine in experimental autoimmune encephalomyelitis report less brain inflammation. This page collects the published research on nicotine and multiple sclerosis, each paper 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

  1. The Papers
  2. PubMed Topic Searches
  3. Connections
  4. Featured Videos

The Papers (18)

Newest first. Study types on this page — Human trial: 2 · Human observational study: 2 · Meta-analysis: 2 · Review: 6 · Animal study: 4 · Cell study: 1 · Chemistry / laboratory method: 1. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.

Evaluation of high-nicotine oral products shows potential to reduce tobacco-related harm by offering satisfying alternatives

Human trial, 2025. This randomised crossover study in Sweden tested three high-strength nicotine pouches (14 mg, 16 mg and 20 mg of nicotine per pouch) against a tobacco snus pouch (16.6 mg) in 27 adults who already used snus or nicotine pouches. The 20 mg pouch delivered the most nicotine into the blood. All four products reduced the urge to use nicotine by similar amounts. Users generally rated the nicotine pouches better than the snus for satisfaction and reward, all products were well tolerated in the short term with no serious adverse events, and the authors concluded that such pouches may help reduce tobacco-related harm for adult smokers.

Chapman F, Morrissey R, McDermott S et al. (2025). Evaluation of high-nicotine oral products shows potential to reduce tobacco-related harm by offering satisfying alternatives. Sci Rep. — PubMed PMID: 41044396 · doi:10.1038/s41598-025-21812-x

Oral adverse event reporting in smoking cessation trials using non-combustible nicotine products: A quality assessment

Review, 2025. Researchers looked at 36 randomized trials in adult smokers that tested nicotine products that are not burned, such as nicotine replacement therapy, e-cigarettes, heated tobacco and smokeless tobacco. They checked how well these trials reported side effects in the mouth, using an adapted harms-reporting checklist. On average the trials met about half of the checklist items (a mean score of 0.52). Only 14% defined what counted as a mouth side effect and 17% measured how severe it was, and reporting did not clearly improve over time. The authors conclude that mouth side effects in these trials are reported in a limited and inconsistent way, and they propose recommendations for better reporting.

La Rosa GRM, Del Giovane C, Minozzi S et al. (2025). Oral adverse event reporting in smoking cessation trials using non-combustible nicotine products: A quality assessment. J Dent. — PubMed PMID: 40858203 · doi:10.1016/j.jdent.2025.106057

Oral health effects of non‑combustible nicotine products: a systematic review and network meta‑analysis of randomized controlled trials

Meta-analysis, 2025. This systematic review and network meta-analysis pooled randomized controlled trials in adult smokers to compare mouth-related side effects of nicotine products that are not burned, such as nicotine replacement gum and mouth spray, e-cigarettes and snus. Of 36 trials included, 21 were combined in the main analysis, and most comparisons with placebo showed no significant difference in mouth side effects. Compared with standard of care, nicotine gum was linked to higher odds of mouth ulcers (canker sores) (OR 2.36), and higher odds of mouth irritation were seen with e-cigarettes (OR 4.06), nicotine mouth spray (OR 4.36), nicotine gum (OR 4.25) and snus (OR 13.56). The authors concluded these products appear generally well tolerated, but the certainty of the evidence was low to very low, and they called for better reporting of mouth side effects in future trials.

La Rosa GRM, Del Giovane C, Minozzi S et al. (2025). Oral health effects of non‑combustible nicotine products: a systematic review and network meta‑analysis of randomized controlled trials. J Dent. — PubMed PMID: 40518041 · doi:10.1016/j.jdent.2025.105910

Demyelination in the medial prefrontal cortex by withdrawal from chronic nicotine causes impaired cognitive memory

Animal study, 2024. This study looked at why memory can get worse when nicotine is stopped after long-term use. In laboratory animals withdrawn from chronic nicotine, the researchers found poorer recognition memory and motor skills. They also found loss of the myelin coating around nerve fibres in the medial prefrontal cortex, a front part of the brain, but not in two reward-related areas, and the worse the myelin loss, the worse the memory. A drug that restores myelin, clemastine, improved the memory problem but not the motor problem, and nicotine directly reduced myelin-making by myelin-forming brain cells. These results come from animals and cells only.

Huang B, Chen Z, Huang F et al. (2024). Demyelination in the medial prefrontal cortex by withdrawal from chronic nicotine causes impaired cognitive memory. Prog Neuropsychopharmacol Biol Psychiatry. — PubMed PMID: 38036034 · doi:10.1016/j.pnpbp.2023.110901

Can alternative nicotine products put the final nail in the smoking coffin?

Review, 2022. This review compared smoking rates in countries where many people use other nicotine products, such as e-cigarettes, heated tobacco and snus, with smoking rates in neighboring countries where these products are less common. The data showed that countries with high use of these products have reached lower smoking rates. The authors suggest that these products may help bring smoking rates down faster than traditional tobacco-control measures that focus only on prevention and quitting.

Fagerström K (2022). Can alternative nicotine products put the final nail in the smoking coffin?. Harm Reduct J. — PubMed PMID: 36456941 · doi:10.1186/s12954-022-00722-5

The effect of nicotine-containing products and fetal sex on placenta-associated circulating midpregnancy biomarkers

Human observational study, 2022. Researchers measured two blood markers of placental health (PlGF and sFlt-1) at 16 to 22 weeks of pregnancy in 2603 Scandinavian women. For 2278 of them, questionnaires recorded their nicotine use, either smoking or snus (moist oral tobacco). Women currently using snus had lower PlGF levels than women who had never used it, and the size of this link depended on the baby's sex. Snus use before or around conception was linked to lower PlGF only in pregnancies with a male fetus, while smoking was not significantly linked to any of the markers. The authors conclude that snus, which users often see as safe, seems to affect placental health in mid-pregnancy differently depending on the baby's sex.

Sundet BK, Kreyberg I, Staff AC et al. (2022). The effect of nicotine-containing products and fetal sex on placenta-associated circulating midpregnancy biomarkers. Biol Sex Differ. — PubMed PMID: 35841068 · doi:10.1186/s13293-022-00443-1

Prenatal nicotine exposure was associated with long-term impact on the cardiovascular system and regulation-Review

Review, 2021. This structured review looked at 34 original studies on nicotine exposure before birth, from any form of nicotine use during pregnancy, and its long-term effects on children's hearts and blood vessels. Together the studies covered 172,696 subjects, from fetuses up to age 19. The reviewers found convincing evidence that children exposed to nicotine before birth had problems with the automatic nervous control of the heart and circulation, and higher blood pressure. Some results conflicted, and some studies may have misclassified who was exposed. The authors concluded that no period, dose or nicotine product was safe during pregnancy and that women should avoid nicotine when planning a pregnancy.

Nordenstam F (2021). Prenatal nicotine exposure was associated with long-term impact on the cardiovascular system and regulation-Review. Acta Paediatr. — PubMed PMID: 33982809 · doi:10.1111/apa.15914

An approach for the extract generation and toxicological assessment of tobacco-free 'modern' oral nicotine pouches

Cell study, 2020. Researchers developed a simple way to soak tobacco-free nicotine pouches in cell culture liquid, giving extracts with a consistent nicotine level that can be tested on cells in the lab. They tested these extracts, along with extracts from a reference snus product and a reference cigarette, on human gum cells and human lung cells, checking cell survival, cell health, oxidative stress and DNA damage. The cigarette extract harmed the cells in most tests, the snus extract had minimal to moderate effects, and the nicotine pouch extract showed little or no effect in any test. These results come only from cells in a dish, and the authors say studies of real-world use and clinical studies in people are still needed.

E B, N E, S B et al. (2020). An approach for the extract generation and toxicological assessment of tobacco-free 'modern' oral nicotine pouches. Food Chem Toxicol. — PubMed PMID: 32998027 · doi:10.1016/j.fct.2020.111713

Maternal use of nicotine products and breastfeeding 3 months postpartum

Human observational study, 2020. This Scandinavian study followed 1837 mothers and used questionnaires during pregnancy and at 3 months after birth to see how many used nicotine products while breastfeeding. At 3 months, 5.6% of the women used snus (a moist oral tobacco), smoked, or did both. Among women who breastfed only, 3.7% used nicotine. The odds of nicotine use were about 2.3 times higher in women who partly breastfed and about 4.6 times higher in women who did not breastfeed. Women who used snus or smoked before or during pregnancy were significantly more likely to use nicotine while breastfeeding.

Nordhagen LS, Kreyberg I, Bains KES et al. (2020). Maternal use of nicotine products and breastfeeding 3 months postpartum. Acta Paediatr. — PubMed PMID: 32274823 · doi:10.1111/apa.15299

Potential effects of using non-combustible tobacco and nicotine products during pregnancy: a systematic review

Review, 2020. This systematic review looked at 21 studies of pregnant women who used smoke-free nicotine products instead of smoking: 12 studies of nicotine replacement therapy, 7 of Swedish snus, 1 of Alaskan iq'mik (a traditional smokeless tobacco) and 1 of e-cigarettes. Each study compared birth outcomes with either no nicotine use or with smoking. Overall, the results suggest that using these products during pregnancy probably raises the risk of some poor birth outcomes, but by less than smoking does. The authors say the research methods are too limited to measure the size of the risk more precisely, and that more studies of the same kind would add little.

Glover M, Phillips CV (2020). Potential effects of using non-combustible tobacco and nicotine products during pregnancy: a systematic review. Harm Reduct J. — PubMed PMID: 32122384 · doi:10.1186/s12954-020-00359-2

Method development and validation of dissolution testing for nicotine release from smokeless tobacco products using flow-through cell apparatus and UPLC-PDA

Chemistry / laboratory method, 2020. Researchers built and validated a laboratory test that measures how quickly nicotine is released from smokeless tobacco into artificial saliva. This was a test-tube study with no people or animals. They used it on several commercial and standard reference products, including a Swedish-style snus pouch, American-style loose moist snuff, loose-leaf chewing tobacco and chopped loose-leaf chewing tobacco. How fast nicotine came out depended on the product's form and cut: snus and loose-leaf released it more slowly than chopped tobacco and loose moist snuff.

Miller JH, Danielson T, Pithawalla YB et al. (2020). Method development and validation of dissolution testing for nicotine release from smokeless tobacco products using flow-through cell apparatus and UPLC-PDA. J Chromatogr B Analyt Technol Biomed Life Sci. — PubMed PMID: 32065955 · doi:10.1016/j.jchromb.2020.122012

Exercise performance increase in smokeless tobacco-user athletes after overnight nicotine abstinence

Human trial, 2019. This randomized trial studied 16 male athletes who regularly use snus, a type of smokeless tobacco. Each athlete did an endurance test to exhaustion twice: once after 12 hours overnight without nicotine, and once in their usual nicotine-satisfied state. Both times they took 1 g of snus (about 8 mg/g of nicotine) 25 minutes before the test. After the night without nicotine, they lasted 13.1% longer (24.1 vs 20.9 minutes); the authors suggest the snus may have relieved withdrawal changes, because going without nicotine had itself raised resting muscle oxygenation by 4% and changed metabolic and heart and circulation measures.

Zandonai T, Tam E, Bruseghini P et al. (2019). Exercise performance increase in smokeless tobacco-user athletes after overnight nicotine abstinence. Scand J Med Sci Sports. — PubMed PMID: 30387193 · doi:10.1111/sms.13333

Small Heat Shock Proteins, Amyloid Fibrils, and Nicotine Stimulate a Common Immune Suppressive Pathway with Implications for Future Therapies

Review, 2019. This review covers research on the alpha-7 nicotinic receptor, the same receptor nicotine acts on, which helps the vagus nerve calm inflammation. The authors describe mouse studies of a small heat shock protein found in multiple sclerosis brain lesions. Mice lacking this protein got sicker in a model of multiple sclerosis, and giving the protein helped in animal models of multiple sclerosis, eye and heart damage from blocked blood flow, and stroke. The protein and similar amyloid fibrils bound to this receptor on immune cells in mice, switching them toward an immune-suppressing state, which the authors suggest could guide future treatments for multiple sclerosis and other disorders.

Rothbard JB, Kurnellas MP, Ousman SS et al. (2019). Small Heat Shock Proteins, Amyloid Fibrils, and Nicotine Stimulate a Common Immune Suppressive Pathway with Implications for Future Therapies. Cold Spring Harb Perspect Med. — PubMed PMID: 30249602 · doi:10.1101/cshperspect.a034223

Nicotine and autoimmunity: The lotus' flower in tobacco

Review, 2018. This review gathers earlier research on how nicotine affects the immune system in autoimmune diseases, including multiple sclerosis, type 1 diabetes, rheumatoid arthritis, sarcoidosis, Behçet's disease and inflammatory bowel diseases. The authors say the findings conflict. Some studies suggest nicotine increases inflammatory signals and makes a type of white blood cell (neutrophils) die and release their contents, which the immune system can then attack as if they were foreign. Other studies suggest nicotine calms inflammation, mainly by binding to the alpha-7 nicotinic receptor, which can increase regulatory T cells and lower inflammatory signals; the authors name addiction and the side effects of each nicotine product sold as the main problems with nicotine.

Gomes JP, Watad A, Shoenfeld Y (2018). Nicotine and autoimmunity: The lotus' flower in tobacco. Pharmacol Res. — PubMed PMID: 29051105 · doi:10.1016/j.phrs.2017.10.005

The relationship of snus use to diabetes and allied conditions

Meta-analysis, 2017. Researchers pooled data from 18 studies to test whether people who use Swedish moist snuff, a smokeless tobacco that delivers at least as much nicotine as smoking, have a higher risk of type 2 diabetes. Overall, current, former and ever users of moist snuff did not have a significantly higher risk, either among never smokers or in the whole population, and use was not linked to related problems such as impaired glucose tolerance. However, never smokers with the highest levels of use had a 65% higher risk of diabetes (relative risk 1.65). The authors say the evidence is somewhat limited and more studies are needed to confirm any possible link.

Lee PN, Thornton AJ (2017). The relationship of snus use to diabetes and allied conditions. Regul Toxicol Pharmacol. — PubMed PMID: 29061372 · doi:10.1016/j.yrtph.2017.10.017

Nicotine modulates neurogenesis in the central canal during experimental autoimmune encephalomyelitis

Animal study, 2015. Researchers studied animals with experimental autoimmune encephalomyelitis, a lab model of multiple sclerosis-like disease, to see whether nicotine changes the nerve stem cells in the spinal cord that help with repair. In untreated animals with the disease, the spinal cord's own repair response was limited and delayed, and the cells lining the spinal cord's central canal multiplied less than in healthy animals. Nicotine lowered inflammation in that area, partly restored the multiplication of those lining cells, and increased the number of oligodendrocytes, the cells that make the protective coating around nerves. These results come only from animals, and the authors present them as a new insight into how nicotine eases this disease model.

Gao Z, Nissen JC, Legakis L et al. (2015). Nicotine modulates neurogenesis in the central canal during experimental autoimmune encephalomyelitis. Neuroscience. — PubMed PMID: 25813705 · doi:10.1016/j.neuroscience.2015.03.031

Activation of the cholinergic anti-inflammatory system by nicotine attenuates neuroinflammation via suppression of Th1 and Th17 responses

Animal study, 2009. This study looked at what happens when nicotine switches on a receptor called the alpha7 nicotinic receptor, which sits on immune cells called T cells. In lab experiments with T cells, nicotine lowered T cell multiplication and cut the release of several inflammatory signalling chemicals. It also shifted the cells toward a less inflammatory type, with one controlling protein falling by 50% and another rising by 350%. T cells from mice bred without this receptor did not respond to nicotine. In mice with an MS-like disease of the brain and spinal cord, nicotine injections (2 mg/kg) made the disease less severe and reduced immune cell entry into the nervous system, nerve coating damage and nerve fibre loss. These results come only from cells and mice.

Nizri E, Irony-Tur-Sinai M, Lory O et al. (2009). Activation of the cholinergic anti-inflammatory system by nicotine attenuates neuroinflammation via suppression of Th1 and Th17 responses. J Immunol. — PubMed PMID: 19846875 · doi:10.4049/jimmunol.0902212

Nicotinic attenuation of central nervous system inflammation and autoimmunity

Animal study, 2009. Researchers gave nicotine to mice with a lab-induced disease that resembles multiple sclerosis, in which the immune system attacks myelin, the protective coating around nerves in the brain and spinal cord. Nicotine significantly delayed and weakened the inflammatory and autoimmune attack. Outside the brain and spinal cord, it slowed the multiplication of the immune T cells that attack myelin and changed the chemical signals those cells release; inside the brain and spinal cord, it reduced the numbers of several inflammatory immune cell types and lowered the surface markers those cells use to drive an immune response. These results are only in mice, and the authors suggest nicotinic receptors could point to new treatment approaches for inflammatory and autoimmune disorders, including those affecting the nervous system.

Shi FD, Piao WH, Kuo YP et al. (2009). Nicotinic attenuation of central nervous system inflammation and autoimmunity. J Immunol. — PubMed PMID: 19155522 · doi:10.4049/jimmunol.182.3.1730

Back to Table of Contents

PubMed Topic Searches

  1. PubMed: Multiple Sclerosis and nicotine (the search this page is built from)

Back to Table of Contents

Connections

Back to Table of Contents