A study from researchers at University Hospital Cardiff Wales in the UK suggests that Crohn’s disease may very well be treated by, get this –

nicotine enemas. That’s right, you heard it here first. Nicotine, as it turns out, has some positive benefits as an anti-inflammatory, particularly within the gut. Ulcerative colitis and Crohn’s disease are both diseases whose primary target is the intestine and particular, the creation of ulcerative lesions that grow and spread creating pain, discomfort and bloody stool. Left untreated, Crohn’s and Ulcerative Colitis can become extremely debilitating and have the ability to trigger other inflammatory diseases such as arthritis. Curiously, it has been observed that those who suffer from ulcerative colitis are almost always non-smokers. Therefore, researchers in University Hospital decided to see what would happen when they applied a nicotine solution to an enema bag and squirted it up the old back side. Turns out, the effects were quite positive.

The study in its complete reproduction is below:

Clinical Study

Nicotine Enemas for Active Crohn’s Colitis:

An Open Pilot Study

J. R. Ingram,1 J. Rhodes,1 B. K. Evans,2 andG. A. O. Thomas1

1Department of Gastroenterology, Cardiff and Vale NHS Trust, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, UK

2 St Mary’s Pharmaceutical Unit, Quadrant Centre, Cardiff Business Park, Llanishen, Cardiff CF14 5RA, UK

Correspondence should be addressed to G. A. O. Thomas, gareth.thomas2@uhw-tr.wales.nhs.uk

Received 7 November 2007; Accepted 19 February 2008

Recommended by JulianWalters

Background. Smoking has a detrimental effect in Crohn’s disease (CD), but this may be due to factors in smoking other than

nicotine. Given that transdermal nicotine benefits ulcerative colitis (UC), and there is a considerable overlap in the treatment

of UC and CD, the possible beneficial effect of nicotine has been examined in patients with Crohn’s colitis. Aims. To assess the

efficacy and safety of nicotine enemas in active Crohn’s colitis. Patients. Thirteen patients with active rectosigmoid CD; 3 patientswere excluded because they received antibiotics. Methods. Subjects were given 6mg nicotine enemas, each day for 4 weeks, in an open pilot study. At the beginning and end of the trial, a Crohn’s disease activity index (CDAI) score was calculated, sigmoidoscopy was performed, and haematological inflammatory markers measured. Results. Mean CDAI decreased from 202 to 153—the score was reduced in 6 patients, unchanged in 3, and increased in one. Frequency of bowel movements decreased in 8 patients and the sigmoidoscopy grade was reduced in 7.Mean C-reactive protein decreased from 22.0 to 12.3mg/L. There were no withdrawals due to adverse events. Conclusions. In this relatively small study of patients with active Crohn’s colitis, 6mg nicotine enemas appeared to be of clinical benefit in most patients. They were well tolerated and safe.

Copyright © 2008 J. R. Ingram et al. This is an open access article distributed under the Creative Commons Attribution License,

which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

1. INTRODUCTION

It is a remarkable epidemiological observation that whilst

ulcerative colitis (UC) is related to nonsmoking [1–4], the

opposite applies to Crohn’s disease (CD). Patients with CD

are more often smokers compared with the general population

[5], and smoking has an adverse effect on the course

of their disease [6]. Several mechanisms for this could be

relevant; components of tobacco smoke, such as oxidizing

chemicals, which, unlike nicotine, have prothrombotic effects,

could exacerbate microvasculature abnormalities and

ischaemia of the bowel wall [7]. It has also been suggested

that CD could be caused by an impaired host response to luminal

bacteria; this, in turn, could be exacerbated by the immunosuppressive

effects of smoking on macrophages [8, 9].

It is likely that different mechanisms are responsible for the

“opposite effects” of smoking in CD and UC, which are in

many other respects similar diseases. The effects of smoking

should not be considered synonymous with nicotine. Nicotine,

as opposed to smoking, may have a beneficial effect in

patients with Crohn’s colitis, given that there is a considerable

overlap in the treatments for the two conditions and nicotine

has been shown to be of benefit in UC. Although the specific

mechanisms underlying this effect remain unclear, nicotine

has a number of actions that could be potentially beneficial,

including effects on the immune system [10] and gutmotility

[11].

A recent Cochrane Review [12] has confirmed benefit

from transdermal nicotine in active UC: a meta-analysis of

two eligible randomized placebo-controlled trials [13, 14] so

far performed showed that after 4 to 6 weeks treatment, 19

of 71 patients treated with transdermal nicotine were in remission

compared to 9 of 70 given placebo (odds ratio 2.56,

95% confidence interval 1.02–6.45). A nicotine enema has

also been developed and found to be of benefit when given as

additional therapy in two uncontrolled pilot studies in active

distal UC [15, 16], but not in a recent randomised controlled

trial [17]. A phase I-II trial of delayed release oral nicotine

has shown promise [18] but a controlled trial is awaited.

The aim of this open pilot study was to examine the efficacy

and safety of nicotine enemas in active distal Crohn’s

colitis.

2 Gastroenterology Research and Practice

2. MATERIALS ANDMETHODS

2.1. Patients

Patients with CD, based on the clinical, endoscopic, and

histological features of Lennard-Jones’ criteria [19], were

recruited from the gastroenterology outpatient department

of a single centre; the key selection criteria were clinical and

sigmoidoscopic evidence of active disease in the rectosigmoid

region. Although the presence of CD in other regions

of the gastrointestinal tract was permitted, the patient’s principal

clinical problem had to relate to active distal colitis. Patients

were not enrolled if they were current smokers, had

other unstablemedical problems, were pregnant or lactating,

had used enemas in the previous week, had changed their

CD therapy with mesalazine, steroids, or antibiotics within

the last 2 weeks, or had changed immunosuppressive therapy

with azathioprine in the previous 3 months. The dosage

of all concomitant medications was kept unchanged during

the study period.