Nicotine and Ulcerative Colitis: The Research

Ulcerative colitis is unusual among inflammatory diseases in being less common in smokers and often flaring after people quit, which led to randomised trials of nicotine patches, enemas and capsules. This page collects the published research on nicotine and ulcerative colitis and the related bowel research, 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.

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  1. The Papers
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The Papers (23)

Newest first. Study types on this page — Human trial: 6 · Human observational study: 1 · Meta-analysis: 2 · Review: 11 · Animal study: 2 · Other: 1. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.

Nicotine is an Immunosuppressant: Implications for Women's Health and Disease

Review, 2024. This review looks at research suggesting that nicotine, the main addictive chemical in tobacco products, can calm or suppress the immune system, and at what that may mean for women's health. The authors say the evidence is mixed. Nicotine may help in some diseases, such as ulcerative colitis, but nicotine use is also a risk factor for some diseases that affect women more often, and the reasons for these links are mostly unclear. They note that little is known about how nicotine's effects on the immune system play out during menopause, a time of increased inflammation, and about its effects on conditions such as Alzheimer's disease and HIV infection in women. Whatever the possible benefits, the authors conclude that quitting nicotine should be a priority in women's medical care, and they call for more research on how nicotine use, the immune system and disease are linked in women.

White AM, Craig AJ, Richie DL et al. (2024). Nicotine is an Immunosuppressant: Implications for Women's Health and Disease. J Neuroimmunol. — PubMed PMID: 39461120 · doi:10.1016/j.jneuroim.2024.578468

Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm

Other, 2020. This paper puts forward a hypothesis; it is not a study. Severe COVID-19 can set off a 'cytokine storm', in which the immune system releases too many inflammatory signals. The authors suggest nicotine might calm that storm, because it switches on a type of nicotinic receptor (α7) that is part of the body's own anti-inflammation pathway, and they note nicotine is already used in ulcerative colitis to reduce inflammation. They point to early clinical reports from China suggesting smokers were statistically less likely to be hospitalized, and they propose nicotine as a possible treatment for severely ill patients, but they did not test it in patients, animals or cells.

Gonzalez-Rubio J, Navarro-Lopez C, Lopez-Najera E et al. (2020). Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm. Front Immunol. — PubMed PMID: 32595653 · doi:10.3389/fimmu.2020.01359

Precision nicotine metabolism-informed care for smoking cessation in Crohn's disease: A pilot study

Human observational study, 2020. Researchers surveyed 1098 patients at an inflammatory bowel disease center and found that 13% of those with Crohn's disease smoked. They then followed 32 smokers with Crohn's disease in a quit-smoking trial. In one group, the quit-smoking medicine was chosen using each person's nicotine metabolite ratio, a measure of how fast the body breaks down nicotine: people were classed as normal or slow metabolizers and offered either nicotine replacement therapy or the drug varenicline. Satisfaction was high (85%). People in the matched-care group chose the medicine that fit their metabolism result more often than people given usual care (100% vs. 64%). Six of the 16 patients prescribed varenicline (37.5%) stopped taking it because of side effects.

Scoville EA, Tindle HA, Wells QS et al. (2020). Precision nicotine metabolism-informed care for smoking cessation in Crohn's disease: A pilot study. PLoS One. — PubMed PMID: 32214373 · doi:10.1371/journal.pone.0230656

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

Nicotine suppresses hyperexcitability of colonic sensory neurons and visceral hypersensivity in mouse model of colonic inflammation

Animal study, 2012. Researchers studied mice with gut inflammation caused by a chemical to see whether nicotine calms overactive pain-sensing nerve cells serving the colon. Those nerve cells stayed overactive for at least 3 weeks, even after the visible signs of inflammation faded. Low-dose nicotine applied to the nerve cells in a dish brought the repeated firing down to a single signal, and nicotine injected under the skin of the mice (2 mg/kg twice a day) reduced the nerve overactivity and the mice's pain responses in the belly. The authors suggest this effect works through nicotinic receptors on nerve cells, but the results come only from mice and isolated mouse nerve cells, not people.

Abdrakhmanova GR, Kang M, Imad Damaj M et al. (2012). Nicotine suppresses hyperexcitability of colonic sensory neurons and visceral hypersensivity in mouse model of colonic inflammation. Am J Physiol Gastrointest Liver Physiol. — PubMed PMID: 22241859 · doi:10.1152/ajpgi.00411.2011

Exploitation of the nicotinic anti-inflammatory pathway for the treatment of epithelial inflammatory diseases

Review, 2006. This review looks at how the nervous system helps control inflammation through a natural pathway. In this pathway, the body's own messenger chemical, acetylcholine, acts on a nicotine-sensitive receptor called the alpha7 nicotinic receptor. Nicotine also switches this receptor on, and it has been studied as a treatment for inflammation of the gut lining, but the authors say it is still debated whether it works for inflammatory bowel disease. They conclude that more research on this pathway is needed to develop better, more targeted treatments for inflammatory conditions such as gum disease, psoriasis, sarcoidosis and ulcerative colitis.

Scott DA, Martin M (2006). Exploitation of the nicotinic anti-inflammatory pathway for the treatment of epithelial inflammatory diseases. World J Gastroenterol. — PubMed PMID: 17167832 · doi:10.3748/wjg.v12.i46.7451

Mechanisms of disease: nicotine--a review of its actions in the context of gastrointestinal disease

Review, 2005. This review looks at how nicotine may act in digestive diseases that are linked to smoking. The authors note that smoking raises the risk of Crohn's disease and peptic ulcer disease and worsens their course. In ulcerative colitis, smoking lowers the risk and can make the disease milder. The review describes nicotine's complex effects on the brain and nervous system, the digestive tract and the immune system, and says these effects likely combine with other factors, such as genes, to shape how these diseases turn out.

Thomas GA, Rhodes J, Ingram JR (2005). Mechanisms of disease: nicotine--a review of its actions in the context of gastrointestinal disease. Nat Clin Pract Gastroenterol Hepatol. — PubMed PMID: 16355159 · doi:10.1038/ncpgasthep0316

A randomized trial of nicotine enemas for active ulcerative colitis

Human trial, 2005. Researchers tested whether nicotine given as an enema helps people with active ulcerative colitis. In this randomized, double-blind study, 104 patients received either 6-mg nicotine enemas or placebo enemas for 6 weeks and kept taking their usual colitis medicines. Remission happened in 14 of 52 patients (27%) on nicotine and 14 of 43 patients (33%) on placebo, so nicotine did no better than placebo. The enemas were well tolerated, and only 1 patient stopped because of a side effect (abdominal pain), but the authors concluded they did not work for active ulcerative colitis.

Ingram JR, Thomas GA, Rhodes J et al. (2005). A randomized trial of nicotine enemas for active ulcerative colitis. Clin Gastroenterol Hepatol. — PubMed PMID: 16271342 · doi:10.1016/s1542-3565(05)00849-9

Transdermal nicotine for induction of remission in ulcerative colitis

Meta-analysis, 2004. This review pooled randomized trials that tested a nicotine skin patch (15 to 25 mg per day) in people with active mild to moderate ulcerative colitis. In two trials comparing the patch with a placebo, 19 of 71 patients on nicotine reached remission after four to six weeks, compared with 9 of 70 on placebo. The patch did no better than standard treatment with oral prednisone or mesalamine, and across all five studies there was no significant overall benefit. Patients on nicotine were significantly more likely to have side effects and to stop treatment because of them, and the authors say these side effects limit its use for some patients.

McGrath J, McDonald JW, Macdonald JK (2004). Transdermal nicotine for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. — PubMed PMID: 15495126 · doi:10.1002/14651858.CD004722.pub2

The pharmacological actions of nicotine on the gastrointestinal tract

Review, 2004. This review looks at research on how nicotine, a major component of cigarette smoke, affects the stomach and intestines. The authors report that nicotine seems to worsen the factors that cause stomach ulcers and to weaken the stomach's natural defenses, slowing ulcer healing. They also report that nicotine and its breakdown products can damage DNA and may help start and promote cancers of the digestive tract by changing how cells grow, die and form new blood vessels, though they say more molecular research is needed. In contrast, they note that clinical trials have shown promising results for nicotine as an add-on treatment for ulcerative colitis, and that more clinical studies are needed to establish its value for this disease.

Wu WK, Cho CH (2004). The pharmacological actions of nicotine on the gastrointestinal tract. J Pharmacol Sci. — PubMed PMID: 15107574 · doi:10.1254/jphs.94.348

Smoking and nicotine in inflammatory bowel disease: good or bad for cytokines?

Review, 1998. This review looks at how smoking and nicotine affect the two main types of inflammatory bowel disease, with a focus on immune signalling molecules called cytokines. The paper notes that smoking appears to help ulcerative colitis but harm Crohn's disease, and that nicotine given through a skin patch had effects in ulcerative colitis similar to smoking. On that basis, nicotine was seen as a possible starting point for developing new drugs for flare-ups of ulcerative colitis that do not respond to corticosteroids. The review covers short-term nicotine use in ulcerative colitis.

Zijlstra FJ (1998). Smoking and nicotine in inflammatory bowel disease: good or bad for cytokines?. Mediators Inflamm. — PubMed PMID: 9705601 · doi:10.1080/09629359891072

A meta-analysis to assess the incidence of adverse effects associated with the transdermal nicotine patch

Meta-analysis, 1998. This study combined results from 35 clinical trials to see how often people using a nicotine skin patch had side effects, comparing 5501 patients on the patch with 3752 patients on a placebo patch. Most trials were testing the patch as an aid to quitting smoking, and the patch clearly helped people stay off cigarettes. Serious heart and circulation problems such as heart attack, stroke, fast or irregular heartbeat and chest pain were rare, and they were not more common in the patch groups than in the placebo groups. Some minor side effects were clearly more common with the patch, especially sleep problems, nausea or vomiting, skin irritation where the patch was worn, and breathing-related symptoms. Nausea and vomiting seemed least common when the patch dose was gradually lowered, and the authors say very large studies would be needed to judge any effect on serious but rare outcomes.

Greenland S, Satterfield MH, Lanes SF (1998). A meta-analysis to assess the incidence of adverse effects associated with the transdermal nicotine patch. Drug Saf. — PubMed PMID: 9565740 · doi:10.2165/00002018-199818040-00005

Nicotine enemas for active ulcerative colitis--a pilot study

Human trial, 1997. This small open pilot study tested nightly enemas containing 6 mg of nicotine for 4 weeks in 22 non-smokers with active ulcerative colitis, who kept taking their usual colitis medicines. Of the 17 patients who finished the month, 16 improved their symptom score, 12 had less urgency and fewer stools, 10 had better scope and biopsy results, and 3 went into full remission; of 6 patients who continued for a second month, 5 improved further and 2 reached full remission. The enemas caused few side-effects, but there was no comparison group, and the authors say controlled studies are needed.

Green JT, Thomas GA, Rhodes J et al. (1997). Nicotine enemas for active ulcerative colitis--a pilot study. Aliment Pharmacol Ther. — PubMed PMID: 9354193 · doi:10.1046/j.1365-2036.1997.00220.x

Pharmacokinetics of nicotine tartrate after single-dose liquid enema, oral, and intravenous administration

Human trial, 1997. Ulcerative colitis mostly affects nonsmokers, and nicotine skin patches can help it but often cause side effects. So researchers tested how much nicotine reaches the blood when given as a liquid enema into the bowel. Thirty healthy volunteers received nicotine as one of four liquid enema types or as a drink, and each person also received a smaller dose into a vein at a separate visit. Only about 15 to 25 percent of the enema doses reached the bloodstream, similar to the 20 percent from the drink and far below the vein dose, and both the enema and the drink were well tolerated. Blood nicotine levels did not predict side effects, and the authors suggest testing nicotine enemas in patients with left-sided ulcerative colitis, because delivering nicotine directly to the colon might limit its side effects elsewhere in the body.

Zins BJ, Sandborn WJ, Mays DC et al. (1997). Pharmacokinetics of nicotine tartrate after single-dose liquid enema, oral, and intravenous administration. J Clin Pharmacol. — PubMed PMID: 9156375 · doi:10.1002/j.1552-4604.1997.tb04320.x

Transdermal nicotine for mildly to moderately active ulcerative colitis. A randomized, double-blind, placebo-controlled trial

Human trial, 1997. This randomized, double-blind trial tested a nicotine skin patch against a placebo patch in 64 non-smoking adults with mild to moderate ulcerative colitis that was still active despite their usual medication. After 4 weeks, 12 of 31 people on the nicotine patch (39%) had clinical improvement, compared with 3 of 33 on placebo (9%). Four people on nicotine stopped treatment because of side effects: skin irritation where the patch was worn (2), nausea (1) and acute pancreatitis (1). The authors concluded that nicotine patches at the highest dose each person could tolerate, up to 22 mg a day, controlled the symptoms of mild to moderate ulcerative colitis over 4 weeks.

Sandborn WJ, Tremaine WJ, Offord KP et al. (1997). Transdermal nicotine for mildly to moderately active ulcerative colitis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. — PubMed PMID: 9054280 · doi:10.7326/0003-4819-126-5-199703010-00004

Nicotine: does it have a role in the treatment of ulcerative colitis?

Review, 1997. This review looked at published research on ulcerative colitis, a long-term inflammatory bowel disease, with a focus on the link between not smoking and the disease and on clinical trials that tested nicotine as a treatment. The authors report that trials suggested nicotine added to standard medicines may improve symptoms in some patients, but nicotine on its own could not be recommended. Patients in the trials often tolerated nicotine poorly and had trouble staying on it long term because of its significant side effects. The authors concluded that the results were disappointing overall, that nicotine cannot be recommended as an add-on or stand-alone treatment, and that more research is needed.

Slyk MP, Frazee LA (1997). Nicotine: does it have a role in the treatment of ulcerative colitis?. Am J Ther. — PubMed PMID: 10423604

Does nicotine have beneficial effects in the treatment of certain diseases?

Review, 1996. This 1996 review looks at why smokers seem less likely to develop ulcerative colitis, Alzheimer's disease and Parkinson's disease, and suggests that nicotine itself may be responsible for this effect. The author explains that nicotine acts on nicotinic receptors in the brain, which are reduced in Alzheimer's and Parkinson's disease, and that these receptors also affect dopamine, a brain chemical involved in Parkinson's disease and Tourette's syndrome. The review says pure nicotine has no known cancer-causing properties and can be given through skin patches or tablets, but it also notes that nicotine has many harmful side effects and that no one should be encouraged to smoke. It concludes that nicotine may have some medical value, or at least may be useful for developing future drugs.

Birtwistle J, Hall K (1996). Does nicotine have beneficial effects in the treatment of certain diseases?. Br J Nurs. — PubMed PMID: 9006184 · doi:10.12968/bjon.1996.5.19.1195

Pilot trial of nicotine patches as an alternative to corticosteroids in ulcerative colitis

Human trial, 1996. This small pilot study tested nicotine skin patches (15 mg a day for 4 weeks) in 10 people with ulcerative colitis. All 10 were having a mild to moderate flare while taking mesalazine, and all had tolerated steroid treatment poorly in the past. In 7 of the 10 patients, the flare went into remission, and the improvement lasted up to 3 months after the patches were stopped. Where endoscopy and tissue samples were done, they confirmed the improvement. The authors suggest nicotine patches may be an alternative to steroids for some patients with mild to moderate flares, but they say it is not known how nicotine works here.

Guslandi M, Tittobello A (1996). Pilot trial of nicotine patches as an alternative to corticosteroids in ulcerative colitis. J Gastroenterol. — PubMed PMID: 8844492 · doi:10.1007/BF02355071

Pharmacology of nicotine: addiction and therapeutics

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

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

Nicotine as a therapeutic drug

Review, 1995. This review looks at whether nicotine itself could be used as a medicine. It finds the strongest evidence is for ulcerative colitis. Whether nicotine helps in Parkinson's or Alzheimer's disease is still unclear, and the authors say more research is needed, including on how safe and well tolerated it is in these diseases. They say nicotine treatment should for now be tried only inside research studies, that no form of tobacco should be used to deliver nicotine, and they urge everyone who uses tobacco to quit.

Westman EC, Levin ED, Rose JE (1995). Nicotine as a therapeutic drug. N C Med J. — PubMed PMID: 7862206

Effect of nicotine on rectal mucus and mucosal eicosanoids

Animal study, 1994. Ulcerative colitis mostly affects non-smokers, so researchers tested how nicotine affects the lining of the rectum in rabbits. Three groups of eight rabbits got nicotine under the skin from a small pump for 14 days, at 0.5, 1.25 or 2 mg/kg/day, and were compared with eight untreated rabbits. In the untreated rabbits, the mucus layer coating the rectum had a median thickness of 36 microns. The lowest dose thinned it to 22 microns, and the highest dose thickened it to 48 microns. Mucus production itself did not change. Nicotine lowered several prostaglandins, which are inflammation-related chemicals, and the lowest dose lowered them most. The authors suggest nicotine might affect colitis through these effects on the bowel's mucus and prostaglandins, but this was shown only in rabbits.

Zijlstra FJ, Srivastava ED, Rhodes M et al. (1994). Effect of nicotine on rectal mucus and mucosal eicosanoids. Gut. — PubMed PMID: 8307477 · doi:10.1136/gut.35.2.247

Transdermal nicotine for active ulcerative colitis

Human trial, 1994. In a randomized, double-blind trial, 72 people with active ulcerative colitis who were already taking their usual medicines wore either a nicotine skin patch or a placebo patch for six weeks; most tolerated doses of 15 to 25 mg per 24 hours. Complete remission occurred in 17 of 35 patients on nicotine compared with 9 of 37 on placebo, and the nicotine group also had better overall and tissue-level grades of colitis, 1.6 fewer stools a day, less abdominal pain and less urgency. Side effects were more common with nicotine (23 patients versus 11), most often nausea, lightheadedness, headache and sleep disturbance. The authors concluded that adding a nicotine patch to standard maintenance therapy improves symptoms of ulcerative colitis.

Pullan RD, Rhodes J, Ganesh S et al. (1994). Transdermal nicotine for active ulcerative colitis. N Engl J Med. — PubMed PMID: 8114833 · doi:10.1056/NEJM199403243301202

Beneficial effects of nicotine

Review, 1991. This 1991 review looks at what pure nicotine, apart from tobacco, does in the body. Nicotine attaches to nicotinic receptors throughout the body, which triggers the release of several brain chemical messengers, especially catecholamines and serotonin. The author lists possible effects of long-term use: reinforcing effects that can drive continued use, lower body weight, better performance, and possible protection against Parkinson's disease, Tourette's disease, Alzheimer's disease, ulcerative colitis and sleep apnea. The paper notes that nicotine in tobacco causes illness and death in millions of people, that these effects vary greatly in how reliable they are, and that this justifies further research into possible medical uses.

Jarvik ME (1991). Beneficial effects of nicotine. Br J Addict. — PubMed PMID: 1859921 · doi:10.1111/j.1360-0443.1991.tb01810.x

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