Nicotine and Ulcerative Colitis: The Research

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 (41)

Newest first. Study types on this page — Human trial: 14 · Human observational study: 1 · Meta-analysis: 1 · Review: 13 · Animal study: 6 · Cell study: 4 · Other: 2. 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

Nicotine improves DSS-induced colitis by inhibiting NLRP3 and altering gut microbiota

Animal study, 2024. Researchers studied nicotine in mice with DSS-induced colitis (a model for ulcerative colitis) and in cell experiments. Nicotine reduced colitis symptoms, shifted gut bacteria toward more beneficial and fewer harmful species, and blocked assembly of an inflammation-related protein complex called NLRP3, which in turn reduced secretion of the inflammatory signal IL-1β.

Zhang YX, Chi XQ, Li M et al. (2024). Nicotine improves DSS-induced colitis by inhibiting NLRP3 and altering gut microbiota. J Asian Nat Prod Res. — PubMed PMID: 38655696 · doi:10.1080/10286020.2024.2331773

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

Nicotine-induced autophagy via AMPK/mTOR pathway exerts protective effect in colitis mouse model

Animal study, 2020. This study tested nicotine in male mice with colitis caused by a chemical in their drinking water, used as a model of ulcerative colitis. Mice given nicotine had less severe colitis than untreated mice: lower disease scores, less tissue damage in the colon, lower levels of inflammatory signals, and better body weight. Nicotine increased autophagy, the cell's internal clean-up process, through a pathway called AMPK/mTOR. When the researchers blocked autophagy with a drug, most of nicotine's protective effect went away. These results come from mice and cell experiments only, not from people.

Gao Q, Bi P, Luo D et al. (2020). Nicotine-induced autophagy via AMPK/mTOR pathway exerts protective effect in colitis mouse model. Chem Biol Interact. — PubMed PMID: 31926917 · doi:10.1016/j.cbi.2020.108943

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 protects against DSS colitis through regulating microRNA-124 and STAT3

Animal study, 2017. Researchers wanted to know why nicotine seems to help ulcerative colitis, so they studied mice with chemically induced colitis, human colon cells grown in the lab, and immune cells taken from the inflamed colon lining of people with ulcerative colitis. Nicotine raised the level of a small regulatory molecule called microRNA-124 and blocked an inflammation switch called STAT3. When the researchers lowered microRNA-124 or blocked STAT3 in other ways, most of nicotine's protective effect in the mice and cells disappeared. The protective effect was shown only in mice and in cells, not in patients, and the authors suggest that the microRNA-124 and STAT3 pathway could be a target for future ulcerative colitis treatments.

Qin Z, Wan JJ, Sun Y et al. (2017). Nicotine protects against DSS colitis through regulating microRNA-124 and STAT3. J Mol Med (Berl). — PubMed PMID: 27709266 · doi:10.1007/s00109-016-1473-5

Novel insights on the effect of nicotine in a murine colitis model

Animal study, 2013. This study used mice with colitis, a bowel inflammation that researchers trigger with a chemical as a model of ulcerative colitis. It tested nicotine given in different ways, and also cotinine, the main substance the body makes when it breaks nicotine down. Low doses of nicotine given by mouth reduced disease severity, tissue damage and the inflammatory signal TNF-alpha in the colon, but high oral doses did not. Long-term nicotine given under the skin or by a slow-release pump did not have this effect, and cotinine by mouth had no significant effect. These results are only in mice, and they suggest that the dose and the way nicotine is given strongly affect whether it protects the colon.

AlSharari SD, Akbarali HI, Abdullah RA et al. (2013). Novel insights on the effect of nicotine in a murine colitis model. J Pharmacol Exp Ther. — PubMed PMID: 23115221 · doi:10.1124/jpet.112.198796

Review article: Ulcerative colitis, smoking and nicotine therapy

Review, 2012. This review looked at published research on smoking, nicotine and ulcerative colitis. Ulcerative colitis is less common in smokers, and smokers who already have the disease tend to have milder disease than ex-smokers and nonsmokers. Evidence is conflicting on whether smokers are hospitalised less, need colon removal less often, or need fewer steroid and immune-suppressing medicines. Nicotine treatment worked to varying degrees in bringing the disease into remission compared with placebo and standard medicines, but side effects were common. The authors conclude that nicotine has limited use as a treatment, perhaps only in selected cases of acute disease that has not responded to standard treatment, and they question whether nicotine is really the part of smoking that changes risk and inflammation.

Lunney PC, Leong RW (2012). Review article: Ulcerative colitis, smoking and nicotine therapy. Aliment Pharmacol Ther. — PubMed PMID: 23072629 · doi:10.1111/apt.12086

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

Anti-inflammatory effects of nicotine in obesity and ulcerative colitis

Review, 2011. This review pulls together existing research on how nicotine may calm inflammation, focusing on obesity and ulcerative colitis. It reports that smokers get ulcerative colitis less often than non-smokers, and that this protective effect seems to work through a nerve-to-immune signaling route that depends on a nicotine receptor called alpha7, found on immune cells. In genetically obese mice and in mice made obese by diet, nicotine improved blood sugar control and insulin sensitivity and reduced inflammation in fat tissue; these obesity results are from animals only. The authors suggest that drugs acting selectively on the alpha7 receptor could be a promising way to treat inflammation in obesity and ulcerative colitis, but they caution that nicotine acts on several types of receptors on the same cell, so its effects may not come from alpha7 alone.

Lakhan SE, Kirchgessner A (2011). Anti-inflammatory effects of nicotine in obesity and ulcerative colitis. J Transl Med. — PubMed PMID: 21810260 · doi:10.1186/1479-5876-9-129

Nicotinic modulation of innate immune pathways via α7 nicotinic acetylcholine receptor

Review, 2010. This review looks at how nicotine affects the body's first-line immune defenses by acting on one type of nicotine receptor, called alpha-7, which is found on both nerve cells and immune cells. The authors summarize evidence that nicotine calms inflammation in several cell types and may help protect nerve cells in diseases linked to inflammation, such as Alzheimer's and Parkinson's disease. They note that nicotine has been tried in clinical trials for some inflammatory diseases, such as ulcerative colitis, but that how it works is still largely unknown. The authors say that understanding this mechanism may help in developing new medicines for infections and nerve-degenerating diseases.

Cui WY, Li MD (2010). Nicotinic modulation of innate immune pathways via α7 nicotinic acetylcholine receptor. J Neuroimmune Pharmacol. — PubMed PMID: 20387124 · doi:10.1007/s11481-010-9210-2

(E)-metanicotine hemigalactarate (TC-2403-12) inhibits IL-8 production in cells of the inflamed mucosa

Cell study, 2007. Researchers tested a nicotine-derived compound called TC-2403-12 on human immune and gut lining cells grown in the lab, including monocytes, granulocytes, colon epithelial cells, and an intestinal cell line. In monocytes, the compound cut production of the inflammatory signal IL-8 to 30% of untreated levels, worked best when cells were exposed for 24 hours beforehand, and this reduction was not caused by cell death or by blocking a specific inflammation pathway (NF-kappaB). IL-8 also tended to decrease in granulocytes and colon epithelial cells, though not in the intestinal cell line tested. No toxic effects were seen at the doses used in these cell experiments.

Spoettl T, Paetzel C, Herfarth H et al. (2007). (E)-metanicotine hemigalactarate (TC-2403-12) inhibits IL-8 production in cells of the inflamed mucosa. Int J Colorectal Dis. — PubMed PMID: 16715250 · doi:10.1007/s00384-006-0135-4

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

Effect of smoking and transdermal nicotine on colonic nicotinic acetylcholine receptors in ulcerative colitis

Human observational study, 2003. Researchers looked for nicotinic acetylcholine receptors, the receptors that nicotine acts on, in the lining of the lower bowel. They examined rectal tissue samples from 55 people without ulcerative colitis and 62 people with inactive ulcerative colitis, both smokers and non-smokers. They also took samples before and after 6 months of treatment from 43 non-smokers with ulcerative colitis who wore either nicotine skin patches or placebo patches. One receptor type (alpha3) was found in many cells of the normal colon, including the lining. Neither smoking nor the nicotine patches changed how much of it was present. People without ulcerative colitis had more of this receptor in the bowel lining than patients did. The authors suggest that nicotine's benefit in ulcerative colitis may come from changes in how the receptor works, not from changes in how many receptors there are.

Richardson CE, Morgan JM, Jasani B et al. (2003). Effect of smoking and transdermal nicotine on colonic nicotinic acetylcholine receptors in ulcerative colitis. QJM. — PubMed PMID: 12509650 · doi:10.1093/qjmed/hcg007

Transport mechanisms of nicotine across the human intestinal epithelial cell line Caco-2

Cell study, 2002. Nicotine has been studied as a possible treatment for ulcerative colitis, a disease that is more common in non-smokers, so this study looked at how nicotine moves across the lining of the gut. The researchers used a lab-grown layer of human intestinal cells. Nicotine moved mostly in one direction, from the blood side back into the gut, which matches the intestine secreting it. This movement was carried by specific transport systems that depend on acidity (pH) and that differ from the known carriers for similar molecules. The authors say these systems could explain how nicotine builds up in the gut from the blood and could help in designing nicotine forms that act directly on the bowel in ulcerative colitis, but these results are from cells only.

Fukada A, Saito H, Inui K (2002). Transport mechanisms of nicotine across the human intestinal epithelial cell line Caco-2. J Pharmacol Exp Ther. — PubMed PMID: 12130712 · doi:10.1124/jpet.102.034629

Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis

Cell study, 2000. In the laboratory, researchers tested nicotine on strips of colon muscle taken from 9 patients with active ulcerative colitis and 18 patients with colorectal cancer, who served as the comparison group. Nicotine relaxed the muscle and weakened its contractions in both groups. The effect was larger in the comparison tissue. When the researchers blocked the body's production of nitric oxide, nicotine's relaxing effect became much smaller. The authors concluded that nicotine works mainly by releasing nitric oxide, which appears to be more active in inflamed ulcerative colitis tissue, and that this may explain part of nicotine's reported benefit in the disease and the bowel movement problems seen in active colitis.

Green JT, Richardson C, Marshall RW et al. (2000). Nitric oxide mediates a therapeutic effect of nicotine in ulcerative colitis. Aliment Pharmacol Ther. — PubMed PMID: 11069313 · doi:10.1046/j.1365-2036.2000.00847.x

Long-term effects of a single course of nicotine treatment in acute ulcerative colitis: remission maintenance in a 12-month follow-up study

Human trial, 1999. This study followed 30 people with mild to moderate ulcerative colitis in the lower colon for 12 months. All had gone into remission after treatment with mesalazine plus either a nicotine skin patch or oral prednisone (a steroid). Over the year, the disease came back in 14 of the 15 people first treated with the steroid, compared with 7 of the 15 treated with the nicotine patch. The authors concluded that remission brought on by nicotine lasted longer than remission brought on by oral steroids.

Guslandi M (1999). Long-term effects of a single course of nicotine treatment in acute ulcerative colitis: remission maintenance in a 12-month follow-up study. Int J Colorectal Dis. — PubMed PMID: 10647637 · doi:10.1007/s003840050221

Nicotine therapy for ulcerative colitis: a review of rationale, mechanisms, pharmacology, and clinical results

Review, 1999. This review looks at why nicotine has been tried as a treatment for ulcerative colitis, a form of inflammatory bowel disease. It explains that smoking protects against developing ulcerative colitis and that nicotine may be the reason for this effect. Controlled trials in people found that nicotine given through a skin patch helped active ulcerative colitis, with side effects including skin irritation where the patch sits, nausea and lightheadedness. Giving nicotine directly into the colon lowered nicotine levels in the blood and reduced side effects, and the authors say it may be of clinical benefit.

Sandborn WJ (1999). Nicotine therapy for ulcerative colitis: a review of rationale, mechanisms, pharmacology, and clinical results. Am J Gastroenterol. — PubMed PMID: 10235187 · doi:10.1111/j.1572-0241.1999.01059.x

Outcome of ulcerative colitis after treatment with transdermal nicotine

Human trial, 1998. Adults with mild to moderate flare-ups of left-sided ulcerative colitis, who were already on mesalamine, were given either a nicotine skin patch or prednisone for 5 weeks, then 15 people from each group who reached remission were followed for 6 months. Over that follow-up, 20% of the nicotine-patch group had a relapse of active colitis compared to 60% of the prednisone group, and relapses happened sooner in the prednisone group.

Guslandi M, Tittobello A (1998). Outcome of ulcerative colitis after treatment with transdermal nicotine. Eur J Gastroenterol Hepatol. — PubMed PMID: 9855069 · doi:10.1097/00042737-199806000-00014

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 dose-ranging pharmacokinetic study of nicotine tartrate following single-dose delayed-release oral and intravenous administration

Human trial, 1997. This study gave 20 healthy adults a delayed-release oral capsule of nicotine (either 3 mg or 6 mg) designed to release in the colon, and compared it to an intravenous dose given to the same people on a separate day. Blood tests showed that only about 41-42% of the oral nicotine reached the bloodstream, mostly because the liver broke much of it down before it could circulate (first-pass metabolism) rather than because it was poorly absorbed in the gut. Blood nicotine levels did not predict who had side effects. The authors note this lower-bioavailability, colon-targeted delivery method could be worth testing in people with ulcerative colitis, since the condition is more common in non-smokers and nicotine given through the skin has been found to help but often causes side effects.

Compton RF, Sandborn WJ, Lawson GM et al. (1997). A dose-ranging pharmacokinetic study of nicotine tartrate following single-dose delayed-release oral and intravenous administration. Aliment Pharmacol Ther. — PubMed PMID: 9354194 · doi:10.1046/j.1365-2036.1997.00236.x

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

Nicotine tartrate liquid enemas for mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy: a pilot study

Human trial, 1997. Ten non-smokers with mild to moderate active ulcerative colitis in the left side of the colon, who had not responded to first-line treatment, used nightly nicotine enemas (a low dose for one week, then a higher dose for three more weeks). Seven completed the study, and 5 of those 7 (71%) showed improvement on exam and in symptoms, though none showed improvement on tissue biopsy. Blood tests showed little to no nicotine actually entered the bloodstream, and the mild side effects reported (nausea, lightheadedness, tremor, trouble sleeping) in 4 of 10 patients were judged unlikely to be caused by the nicotine itself. The researchers concluded the treatment appeared safe and helpful in this small pilot and said larger placebo-controlled trials were needed to confirm the results.

Sandborn WJ, Tremaine WJ, Leighton JA et al. (1997). Nicotine tartrate liquid enemas for mildly to moderately active left-sided ulcerative colitis unresponsive to first-line therapy: a pilot study. Aliment Pharmacol Ther. — PubMed PMID: 9305473 · doi:10.1046/j.1365-2036.1997.00208.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

In-vivo effect of nicotine on cytokine production by human non-adherent mononuclear cells

Human trial, 1996. Eleven healthy male non-smokers wore nicotine patches for seven days, with the dose increasing from 5 mg up to 15 mg per day. Blood immune cells (non-adherent mononuclear cells) were tested before and after treatment: nicotine significantly reduced the cells' production of the signaling protein IL-10, but did not change their production of IL-2 or TNF alpha. The researchers were trying to explain why nicotine patches help ulcerative colitis but smoking seems to worsen Crohn's disease, based on these two conditions' different immune cell patterns.

Madretsma S, Wolters LM, van Dijk JP et al. (1996). In-vivo effect of nicotine on cytokine production by human non-adherent mononuclear cells. Eur J Gastroenterol Hepatol. — PubMed PMID: 8930570 · doi:10.1097/00042737-199610000-00016

Nicotine inhibits the in vitro production of interleukin 2 and tumour necrosis factor-alpha by human mononuclear cells

Cell study, 1996. Researchers took white blood cells from healthy volunteers and treated them in the lab with nicotine or a steroid drug before stimulating them. Both nicotine and the steroid significantly reduced the cells' production of two immune signaling molecules, interleukin 2 and tumor necrosis factor-alpha; nicotine's effect reached about half the strength of the steroid's, at nicotine levels similar to those found in the blood of smokers. The authors suggest this immune-dampening effect on blood cells may help explain why nicotine has a beneficial symptomatic effect in ulcerative colitis.

Madretsma GS, Donze GJ, van Dijk AP et al. (1996). Nicotine inhibits the in vitro production of interleukin 2 and tumour necrosis factor-alpha by human mononuclear cells. Immunopharmacology. — PubMed PMID: 8913794 · doi:10.1016/0162-3109(96)00122-1

Transdermal nicotine compared with oral prednisolone therapy for active ulcerative colitis

Human trial, 1996. 61 adults with active ulcerative colitis were randomly assigned to transdermal nicotine patches (15-25 mg daily) or 15 mg prednisolone daily for 6 weeks. In the 43 who finished the trial, 6 of 19 on nicotine reached full remission seen on sigmoidoscopy versus 14 of 24 on prednisolone, a difference that was not statistically significant, and prednisolone produced a significantly bigger improvement in the sigmoidoscopy score. More people dropped out of the nicotine group, and nicotine caused more side effects (nausea, light-headedness, tremor) than prednisolone. The study authors concluded nicotine alone gave only modest benefit and was less effective than prednisolone.

Thomas GA, Rhodes J, Ragunath K et al. (1996). Transdermal nicotine compared with oral prednisolone therapy for active ulcerative colitis. Eur J Gastroenterol Hepatol. — PubMed PMID: 8864674

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

Society for Research on Nicotine and Tobacco

Other, 1996. This is a summary of the first scientific meeting of a nicotine and tobacco research society, covering many different topics rather than one study. It describes talks on genetic factors affecting nicotine use, individual differences in how people process nicotine, and early research into nicotine-based or nicotine-like drugs being studied for schizophrenia, Alzheimer's disease, Parkinson's disease, Tourette's syndrome, and ulcerative colitis.

Perkins KA, Benowitz N, Henningfield J et al. (1996). Society for Research on Nicotine and Tobacco. Addiction. — PubMed PMID: 8822021 · doi:10.1046/j.1360-0443.1996.91112915.x

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

Is transdermal nicotine associated with cardiovascular risk?

Human trial, 1995. A randomized, double-blind trial gave transdermal nicotine patches (or a placebo patch) to 45 non-smokers with ulcerative colitis in remission who were already on standard colitis therapy, to see how it affected blood-clotting markers and blood fats over 12 weeks. Nicotine lowered one clotting marker, plasma fibrinogen, but had no effect on platelet activation, blood vessel lining damage markers, white blood cell count, or blood fat levels. The authors say this raises the possibility that transdermal nicotine could favorably affect cardiovascular risk factors, but they describe this as something that needs further study.

Thomas GA, Davies SV, Rhodes J et al. (1995). Is transdermal nicotine associated with cardiovascular risk?. J R Coll Physicians Lond. — PubMed PMID: 8847680

Transdermal nicotine as maintenance therapy for ulcerative colitis

Human trial, 1995. In a six-month randomized, double-blind trial, 80 people with ulcerative colitis in remission were given either transdermal nicotine patches (building up to 15 mg for 16 hours daily) or placebo patches, after stopping their mesalamine treatment. The two groups had no significant difference in the number of relapses. More side effects (like nausea, lightheadedness, and itching) were reported in the nicotine group than the placebo group, and more people on nicotine dropped out early due to side effects.

Thomas GA, Rhodes J, Mani V et al. (1995). Transdermal nicotine as maintenance therapy for ulcerative colitis. N Engl J Med. — PubMed PMID: 7885427 · doi:10.1056/NEJM199504133321503

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

Nicotine inhibits cytokine synthesis by mouse colonic mucosa

Animal study, 1995. Researchers gave nicotine to mice and measured inflammatory substances in the colon lining. Several lipid-based inflammatory mediators (prostaglandins, leukotrienes, platelet activating factor) were unchanged, but nicotine completely stopped the colon tissue from making two inflammatory proteins, interleukin-1 beta and tumor necrosis factor alpha. The authors suggest this blocking effect could explain why smoking and nicotine have been linked to benefits in ulcerative colitis.

Van Dijk JP, Madretsma GS, Keuskamp ZJ et al. (1995). Nicotine inhibits cytokine synthesis by mouse colonic mucosa. Eur J Pharmacol. — PubMed PMID: 7664807 · doi:10.1016/0014-2999(95)00211-3

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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PubMed Topic Searches

1. PubMed: Ulcerative Colitis and nicotine (the search this page is built from)

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Connections

• The Gut Barrier & Your Microbiome — interactive animation
• Nicotine: The Research
• Dr. Bryan Ardis on this subject — his claims, presented on their own pages and kept separate from this research collection
• The Nicotine Patch, animated
• Nicotinic Acetylcholine Receptors
• Cigarette Smoke — what burnt tobacco adds that nicotine alone does not
• Brain and Memory
• Mood and Mental Health
• Inflammation and Immunity
• Cancer Research
• Heart and Blood Vessels
• Metabolism and Weight
• Addiction and Withdrawal
• Patches, Gum and Delivery

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