Crohn's Disease

An estimated 500,000 Americans have Crohn's disease, an inflammatory bowel disease (IBD) that causes chronic inflammation of the intestinal tract. Like ulcerative colitis, another common IBD, Crohn's disease can be both painful and debilitating and sometimes may lead to life-threatening complications. There's no known medical cure for Crohn's disease. However, therapies are available that may greatly reduce the signs and symptoms of Crohn's disease and even bring about a long-term remission.

Monday, March 10, 2014

CBD (Cannabidiol) Use For Chrohn's Disease and Colitis

Cannabidiol in inflammatory bowel diseases: a brief overview.

Abstract

This minireview highlights the importance of cannabidiol (CBD) as a promising drug for the therapy of inflammatory bowel diseases (IBD). Actual pharmacological treatments for IBD should be enlarged toward the search for low-toxicityand low-cost drugs that may be given alone or in combination with the conventional anti-IBD drugs to increase their efficacy in the therapy of relapsing forms of colitis. In the past, Cannabis preparations have been considered new promising pharmacological tools in view of their anti-inflammatory role in IBD as well as other gut disturbances. However, their use in the clinical therapy has been strongly limited by their psychotropic effects. CBD is a very promising compound since it shares the typical cannabinoid beneficial effects on gut lacking any psychotropic effects. For years, its activity has been enigmatic for gastroenterologists and pharmacologists, but now it is evident that this compound may interact at extra-cannabinoid system receptor sites, such as peroxisome proliferator-activated receptor-gamma. This strategic interaction makes CBD as a potential candidate for the development of a new class of anti-IBD drugs.

Cannabidiol reduces intestinal inflammation through the control of neuroimmune axis.

Abstract

Enteric glial cells (EGC) actively mediate acute and chronic inflammation in the gut; EGC proliferate and release neurotrophins, growth factors, and pro-inflammatory cytokines which, in turn, may amplify the immune response, representing a very important link between the nervous and immune systems in the intestine. Cannabidiol (CBD) is an interesting compound because of its ability to control reactive gliosis in the CNS, without any unwanted psychotropic effects. Therefore the rationale of our study was to investigate the effect of CBD on intestinal biopsies from patients with ulcerative colitis (UC) and from intestinal segments of mice with LPS-induced intestinal inflammation. CBD markedly counteracted reactive enteric gliosis in LPS-mice trough the massive reduction of astroglial signalling neurotrophin S100B. Histological, biochemical and immunohistochemical data demonstrated that S100B decrease was associated with a considerable decrease in mast cell and macrophages in the intestine of LPS-treated mice after CBD treatment. Moreover the treatment of LPS-mice with CBD reduced TNF-α expression and the presence of cleaved caspase-3. Similar results were obtained in ex vivo cultured human derived colonic biopsies. In biopsies of UC patients, both during active inflammation and in remission stimulated with LPS+INF-γ, an increased glial cell activation and intestinal damage were evidenced. CBD reduced the expression of S100B and iNOS proteins in the human biopsies confirming its well documented effect in septic mice. The activity of CBD is, at least partly, mediated via the selective PPAR-gamma receptor pathway. CBD targets enteric reactive gliosis, counteracts the inflammatory environment induced by LPS in mice and in human colonic cultures derived from UC patients. These actions lead to a reduction of intestinal damage mediated by PPARgamma receptor pathway. Our results therefore indicate that CBD indeed unravels a new therapeutic strategy to treat inflammatory bowel diseases.

Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa, is protective in a murine model of colitis.

Abstract

Inflammatory bowel disease affects millions of individuals; nevertheless, pharmacological treatment is disappointingly unsatisfactory. Cannabidiol, a safe and non-psychotropic ingredient of marijuana, exerts pharmacological effects (e.g., antioxidant) and mechanisms (e.g., inhibition of endocannabinoids enzymatic degradation) potentially beneficial for the inflamed gut. Thus, we investigated the effect of cannabidiol in a murine model of colitis. Colitis was induced in mice by intracolonic administration of dinitrobenzene sulfonic acid. Inflammation was assessed both macroscopically and histologically. In the inflamed colon, cyclooxygenase-2 and inducible nitric oxide synthase (iNOS) were evaluated by Western blot, interleukin-1beta and interleukin-10 by ELISA, and endocannabinoids by isotope dilution liquid chromatography-mass spectrometry. Human colon adenocarcinoma (Caco-2) cells were used to evaluate the effect of cannabidiol on oxidative stress. Cannabidiol reduced colon injury, inducible iNOS (but not cyclooxygenase-2) expression, and interleukin-1beta, interleukin-10, and endocannabinoid changes associated with 2,4,6-dinitrobenzene sulfonic acid administration. In Caco-2 cells, cannabidiol reduced reactive oxygen species production and lipid peroxidation. In conclusion, cannabidiol, a likely safe compound, prevents experimental colitis in mice.

Topical and systemic cannabidiol improves trinitrobenzene sulfonic acid colitis in mice.

Abstract

BACKGROUND/AIMS:

Compounds of Cannabis sativa are known to exert anti-inflammatory properties, some of them without inducing psychotropic side effects. Cannabidiol (CBD) is such a side effect-free phytocannabinoid that improves chemically induced colitis in rodents when given intraperitoneally. Here, we tested the possibility whether rectal and oral application of CBD would also ameliorate colonic inflammation, as these routes of application may represent a more appropriate way for delivering drugs in human colitis.

METHODS:

Colitis was induced in CD1 mice by trinitrobenzene sulfonic acid. Individual groups were either treated with CBD intraperitoneally (10 mg/kg), orally (20 mg/kg) or intrarectally (20 mg/kg). Colitis was evaluated by macroscopic scoring, histopathology and the myeloperoxidase (MPO) assay.

RESULTS:

Intraperitoneal treatment of mice with CBD led to improvement of colonic inflammation. Intrarectal treatment with CBD also led to a significant improvement of disease parameters and to a decrease in MPO activity while oral treatment, using the same dose as per rectum, had no ameliorating effect on colitis.

CONCLUSION:

The data of this study indicate that in addition to intraperitoneal application, intrarectal delivery of cannabinoids may represent a useful therapeutic administration route for the treatment of colonic inflammation.

CBD is now legal and available in all 50 States in America.

You Can get a Great Overview Here

Friday, November 04, 2005

External Link Sites

Crohn's Disease US National Institute of Diabetes and Digestive and Kidney Diseases
Crohn's Disease - MayoClinic.com
Crohn's Disease - WebMed
Crohn's Disease Clinical and Alternative Treatment
Crohn's Disease - HealthAtoZ
How the disease came to be known as Crohn's disease
Organizations
National Association of Colitis and Crohn's Disease
CrohnsZone.org - Self-help Group
Crohn's and Colitis Foundation of America
Crohn's and Colitis Foundation of Canada
Paratuberculosis Awareness and Research Association, inc. (subscribes to the view that Crohn's is caused by infectious agents)

History and name

History and name

Crohn's disease was first described by Giovanni Battista Morgagni (1682-1771), and subsequent cases were described by John Berg in 1898, and by Polish surgeon Antoni Leśniowski in 1904.

Scottish physician T. Kennedy Dalziel described nine cases in 1913. Burrill Bernard Crohn, an American gastroenterologist, described fourteen cases in 1932, characterizing the disease as "Terminal ileitis: A new clinical entity"; the description was changed to "Regional ileitis" on publication.

It is by virtue of alphabetization rather than contribution that Crohn's name appeared as first author: because this was the first time the condition was reported in a widely-read journal, and the disease has come to be known as Crohn's disease for reasons of publicity rather than precedence.

In Poland the disease is known as Leśniowski-Crohn disease. In Germany the disease is known as Morbus Crohn (which means Crohn morbility or disease).

Dietary Suggesttions

Paying close attention to diet can help reduce the number and severity of flare-ups for many sufferers. Patients are encouraged to follow a nutritious diet and limit any foods that seem to worsen symptoms. Individual reactions vary. Some foods commonly avoided by Crohn's patients are:
Dairy foods.

Some people are lactose intolerant (unable to digest the sugar lactose, found in milk products). Taking lactase tablets or specially prepared dairy products may help. Note: Many lactose-intolerant patients are still able to eat yogurt with active cultures, which may even be helpful
Foods high in fiber, but because a high-fiber diet has other benefits, this might be considered only during flare-ups.

Foods associated with inflammation (alcohol, hot spices, and caffeine).
Saturated fats, found in meat and dairy products. However some fats such as in fish oil may actually be helpful.
Products containing corn or gluten (those made from wheat, oats, barley, or triticale).
Common allergenic foods, such as soy, eggs, peanuts, tomatoes.
Gas-producing foods such as cabbage family vegetables (broccoli, cabbage, cauliflower and brussels sprouts), dried peas and lentils, onions and chives, peppers and carbonated drinks
Foods that may irritate the intestine (particularly the cabbage family vegetables).

Simple sugars,
Dried fruits or high-sugar fruits, such as grapes, watermelon, or pineapple.
Sorbitol (a type of sweetener)
And some foods may also be beneficial:
Fluids to keep the body hydrated and prevent constipation
Fruits may be protective
A high protein diet with lean meats

Other advice:
Trying small frequent meals may also help.
There have also been some suggestions that prebiotics such as psyllium may help in the healing process. Furthermore, probiotics (live culture) may also be helpful in aiding recovery of the intestines.

People With Crohn's Speak Out About Diets

Diet changes? I've suffered Chrohn's since I was a teenager, and as far as I can tell diet makes absolutely no difference to my symptoms. I'm told my experience is reasonably typical in that sense (though people who've had surgery are often a little restricted in what they can eat). --Robert Merkel 12:22 Jan 24, 2003 (UTC)

Hmm. You mean to tell me you can eat lots and lots of fiber and roughage, including things like corn on the cob, broccoli, mushrooms, etc. without a worsening of symptoms? I think that would be pretty atypical. Chadloder 12:24 Jan 24, 2003 (UTC)

My symptoms get worse with some foods, but I don't always care. Some things are worth it :).
Aren't Asacol and Pentasa different brand names for the same stuff? I remember, back when Asacol was somewhat efficacious, being curious as to why Pentasa made me throw up and Asacol didn't when according to the labels on the bottles they're both mesalamine. --Calieber 20:12, 29 Sep 2003 (UTC

Thursday, November 03, 2005

Living with Chrones Crohn's Disease

This is an article written from personal experience with Chrones Crohns disease.

Crohn's is an autoimmune disease. By this, we mean, that the body thinks that another part of the body is a foreign object. Because of this, the immune system begins to attack that part of the body trying to kill it (like rheumatoid arthritis). Crohn's is a disease where the immune system believes that the intestines and stomach is a foreign object. It is reported by the Crohn's and Colitis Foundation of America that one million Americans suffer with Crohn's and Colitis.

Mostly, this manifests itself in severe stomach pains mainly after eating meals, nausea, vomiting, diarrhea and rectal bleeding. Often, patients cannot finish their meals without pain. In these cases, a meal substitution like Ensure helps. Another over-the-counter product that helps is Pedialyte. These help the body from becoming dehydrated.

Many people who have Crohn's disease first noticed symptoms when they were entering puberty; the time is about the same for both boys and girls. For women, menopause seems to end their troubles with Crohn's. Often remission is achieved with medications, but for some, there is no remedy.

If you have any of these symptoms, please contact your doctor to schedule an appointment to have a colonoscopy. A colonoscopy is a flexible scope that enters the intestines through the rectum. During this procedure, you will be sedated. The doctor can tell if there are any tears or inflammation in the intestines. Also, he may take a tissue sample to see if there are any abnormalities. A blood test can confirm if there is active Crohn's. Another test is a CT Scan on the stomach. This requires the patient to drink Barium Sulfate before the test. If Crohn's disease has been found, today there are many treatments to help the patient.

In the late 80's to earlier 90's, there were not many treatments for Crohn's. Prednisone was, and still is the most common drug used to treat this disease. One that was also available was called Rowasa, a nightly enema, which has to be retained. Another drug is called Asacol, which is the tablet form of Rowasa. Rowasa, Asacol and Pentasa are 5-ASA drugs (mesalamine). They are by-products of sulfafazine and aspirin.

In the early 60's, the use of Imuran (azithoprine) began for Crohn's began. It was originally used for kidney transplant patients to keep them from rejecting the organ. Other drugs in this classification are Purinethol (6-mercaptopurine or 6-MP) and Methotrexate. 6-MP was originally used to treat leukemia. These drugs are immuno-suppressants. The wide use of these drugs for Crohn's was not accepted until the early 90's.

There is a new drug that was just FDA approved in Aug 1998 that is called Remicade (Inflixamab). This drug is similar to chemotherapy. It is also being used for rheumatoid arthritis. For some, this is their only hope of having a normal life. Personally, this was my last resort.
When in remission, Crohn's patients can continue in school, hold a full time job, raise a family and live life as a normal person. For more information on Crohn's disease and other related stomach illnesses, visit the Crohn's and Colitis Foundation of America web site.
Written by someone who has suffered for 10 years with this disease.

Chrohn's Information Center

Trial Drug Looks Promising for Crohn's

WEDNESDAY, Nov. 10 (HealthDayNews) -- A genetically engineered antibody that blocks an immune system molecule has produced promising results in its first use against Crohn's disease, researchers report.
The antibody targets interleukin-12, whose proper purpose is defending against infection. In Crohn's disease, a flawed response to bacterial infection causes painful bowel inflammation; an as yet unidentified genetic factor makes the system go wrong, setting off a chain of molecular events that results in inflammation.
Although the study was designed only to test the safety of giving the anti-interleukin-12 treatment to human patients, "it was really gratifying to see that you could show a significant response" in the form of reduced symptoms, said study author Dr. Peter J. Mannon, head of the clinical inflammatory bowel diseases research unit at the National Institute of Allergy and Infectious Diseases. The report appears in the Nov. 11 issue of the New England Journal of Medicine.

Crohn's disease is one of two conditions that cause chronic inflammation of the intestinal tract and which together affect about 1 million Americans. The other is ulcerative colitis, which usually attacks the large intestine; Crohn's disease generally attacks the small intestine.
Research has indicated that the attack in both diseases is due to an improper response by immune system cells, which release excess amounts of cytokines, molecules that attack the intestinal cells and cause inflammation. One cytokine-blocking antibody, infliximab (brand name Remicade), which prevents production of a cytokine called tumor necrosis factor alpha, has been approved for treatment of Crohn's disease. It has been found to be only partially effective.
"We can think about inflammation as a chain reaction," Mannon said. Tumor necrosis factor alpha comes into action toward the end of the chain, he said, and "if we can intervene early in that process, we might have more benefit."

Interleukin-12 acts "higher in the inflammatory pathway," and blocking it can be more effective than blocking tumor necrosis factor, said Dr. Lloyd Mayer, chairman of the immunobiology center at Mount Sinai School of Medicine in New York, which participated in the trial.
The study included 79 patients with Crohn's disease. Some got seven weekly injections of 3 milligrams of the antibody per kilogram of body weight, some got injections of 1 milligram of the antibody per kilogram of body weight, and others got an inactive substance.

More than 70 percent of the patients who got the higher doses of the antibody experienced remissions, the researchers reported. Blood tests showed decreased production of interleukin-12 and other cytokines, such as tumor necrosis factor alpha, in those patients. There were no significant side effects.
The study is just a starting point, Mannon said, because the small number of participants makes it difficult to assess the lasting value of the treatment.

"There may be a powerful underlying effect," he said. "That needs to be tested in a larger study."
SOURCES: Peter J. Mannon, M.D., M.P.H., head, clinical inflammatory bowel diseases research unit, National Institute of Allergy and Infectious Diseases, Bethesda, Md.; Lloyd Mayer, M.D., chairman, immunobiology center, Mount Sinai School of Medicine, New York City; Nov. 11, 2004, New England Journal of Medicine

Calming Crohn's Disease with New Drug

Background: Crohn's disease is a kind of inflammatory bowel disease (IBD) that affects about a million people in North America. It is thought that overproduction of inflammatory substances called cytokines may cause the chronic intestinal inflammation of Crohn's disease. This has led to the development of agents to block the production of key cytokines. The first was Remicade (infliximab). It blocks a cytokine called tumor necrosis factor alpha.

Summary: A new agent, a monoclonal antibody directed against a cytokine known as interleukin-12 was given subcutaneously (below the skin) for seven weeks to people with Crohn's disease. A good clinical response was found in the group that received the higher dose of the antibody that was tested.

Comment: Although this agent looks good so far, questions remain regarding its long-term safety, especially since cytokines are important in combating infection. The reactivation of tuberculosis in people who received Remicade is an example of the potential for harm due to the suppression of the normal immune response. Other concerns that will need to be addressed include the long-term risk of cancer and, in the long run, the possibility of making Crohn's disease worse.

What Is Chrohn's Disease ?

Crohn's disease: A chronic inflammatory disease, primarily involving the small and large intestine, but which can affect other parts of the digestive system as well. It is named for Burrill Crohn, the American gastroenterologist who first described the disease in 1932.
Crohn disease is usually diagnosed in persons in their teens or twenties, but can come to the fore at any point in life. It can be a chronic, recurrent condition or can cause minimal symptoms with or even without medical treatment.
In mild forms, Crohn disease causes small scattered shallow crater- like areas (erosions) called aphthous ulcers in the inner surface of the bowel. In more serious cases, deeper and larger ulcers can develop, causing scarring and stiffness and possibly narrowing of the bowel, sometimes leading to obstruction. Deep ulcers can puncture holes in the bowel wall, leading to infection in the abdominal cavity (peritonitis) and in adjacent organs.
Crohn disease comes in many forms. Involvement of the large intestine (colon) only is called Crohn colitis or granulomatous colitis, while involvement of the small intestine alone is called Crohn enteritis. The most common part of the small intestine to be affected by Crohn disease is the last portion, called the ileum. Active disease in this area is termed Crohn ileitis. When both the small intestine and the large intestine are involved, the condition is called Crohn enterocolitis (or ileocolitis). Other descriptive terms may be used as well.
Abdominal pain, diarrhea, vomiting, fever, and weight loss are common symptoms. Crohn disease can be associated with reddish tender skin nodules, and inflammation of the joints, spine, eyes, and liver. Diagnosis is commonly made by x-ray or colonoscopy. Treatment includes medications that are anti-inflammatories, immune suppressors or antibiotics. Surgery can be necessary in severe cases.
Genetic factors contribute to the causation of Crohn disease. One of the genes has been shown to be on chromosome 14 in region 14q11-12.

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