CROHN'S/ IBS/ ULCERATIVE COLITIS & Cannabis studies
Science & Research
Cannabis for Crohn's Disease
Cannabis for Crohn's Disease
Undated - Anecdotal - MARIJUANA AND IRRITABLE BOWEL SYNDROME (IBS)
1973 - Study - Intestinal obstruction by an unusual foreign body
1997 - Anecdotal - Marijuana and Crohn's Disease
2005 - News - Crohn's Patients Report Symptomatic
2005 - News - Cannabis may soothe inflamed bowels
2005 - News - Bowel Study Backs Cannabis Drugs
2006 - News - Cannabis Helps Ulcers And Crohn's Disease
2006 - News - Synthetic THC Eases Stomach Cramping, Study Says
2008 - News - Anti-inflammatory compound from cannabis found in herbs
2009 - Study - Cannabinoids in intestinal inflammation and cancer
2009 - News ~ Medical Marijuana and Crohn's Disease.
2009 - News ~ Cannabis for Ulcerative Colitis and Crohn's Disease treatment.
2010 - Study ~ The
Cannabinoid 1 Receptor (CNR1) 1359 G/A Polymorphism Modulates
Susceptibility to Ulcerative Colitis and the Phenotype in Crohn's
2011 - Study ~ Treatment of Crohn's disease with cannabis: an observational study.
Cannabis may soothe inflamed bowels
Cannabis-based drugs could offer treatment hope to sufferers of inflammatory bowel disease, UK researchers report.
Cannabis smokers with inflammatory bowel disease (IBD) have often claimed that smoking a joint seems to lessen their symptoms. So a group of researchers from Bath University and Bristol University, both in the UK, decided to explore the clinical basis for the claims. "There is quite a lot of anecdotal evidence that using cannabis seems to reduce the pain and frequency of Crohn’s disease and ulcerative colitis, so we decided to see if we could find out what was going on there," says Karen Wright, a pharmacologist at Bath University. "Historically, it was smoked in India and China centuries ago for its gastrointestinal properties". The chronic conditions, known collectively as IBD, are caused by an over-active immune system which produces severe inflammation in areas of the gastrointestinal tract. Up to 180,000 people in the UK are thought to have colitis or Crohn’s disease and suffer symptoms of pain, urgent diarrhoea, severe tiredness and loss of weight. Repeated attacks can lead to scarring of the colon and fibrosis to the extent that the bowel narrows to form a stricture, for which a colonectomy - the surgical removal of the bowel - is the only cure.
Reports that cannabis eased IBD symptoms indicated the possible existence of cannabinoid receptors in the intestinal lining, which respond to molecules in the plant-derived chemicals. Wright and colleagues grew sections of human colon and examined them in vitro. To their surprise, the team discovered CB1 cannabinoid receptors - which are known to be present in the brain - in the endothelial cells which line the gut. "I think they must be involved in repairing the lining of the gut when it is damaged," Wright says. She deliberately damaged the cells to cause inflammation of the gut lining and then added synthetically produced cannabinoids."The gut started to heal: the broken cells were repaired and brought back closer together to mend the tears," she told New Scientist. Wright believes that in a healthy gut, natural endogenous cannabinoids are released from endothelial cells when they are injured, which then bind to the CB1 receptors. The process appears to set off a wound-healing reaction. "When people use cannabis, the cannabinoids bind to these receptors in the same way," she said.
Previous studies have shown that CB1 receptors located on the nerve cells in the gut respond to cannabinoids by slowing gut motility, therefore reducing the painful muscle contractions associated with diarrhoea. But Wright and her team also discovered another cannabinoid receptor, CB2, in the guts of IBD sufferers, which was not present in healthy guts. These receptors, which also respond to chemicals in cannabis, appear to be associated with apoptosis - programmed cell death - and may have a role in suppressing the overactive immune system and reducing inflammation by moping up excess cells, she suggests. "Ideally we would want to be able to stimulate the body’s own endogenous cannabinoid system, which might become dysregulated during long-term inflammation. Knowing more about how this system actually works will help us to look for therapeutic targets," Wright says. "We are not advocating cannabis use, particularly as smoking tobacco exacerbates Crohn’s disease and many smokers of cannabis use tobacco as well." "Anything that offers hope is good news for sufferers of IBD," says a spokesperson from the National Association for Colitis and Crohn’s Disease, commenting on the research.
Source: new scientist
Journal reference: Gastroenterology
In the Human Colon: Cannabinoids Promote Epithelial Wound Healing
Crohn's Patients Report Symptomatic Relief From Cannabis
NORML, 18th November 2005
Patients with Crohn's disease report subjective benefits from cannabis, including pain relief and increased appetite, according to survey data published in the autumn issue of O'Shaughnessy's: The Journal of Cannabis in Clinical Practice.
Twelve patients were self-selected to participate in the survey, which assessed subjective changes in volunteers' symptoms after the use of cannabis. "For all signs and symptoms evaluated in the study, the patients described marked improvements with the use of cannabis," concluded co-author Jeff Hergenrather of the California Society for Cannabis Clinicians. "Beneficial effects were reported for appetite, pain, nausea, vomiting, fatigue, activity, and depression. Patients also reported that cannabis use resulted in weight gain, fewer stools per day and fewer flare-ups of less severity."
Authors also found that patients' use of cannabis was associated with a decrease in their use of other pharmaceutical medicines.
The pilot study is the first to examine the therapeutic use of cannabis in patients with Crohn's disease.
Pre-clinical data published this past summer in the journal Gastroenterology found that cannabinoids may promote healing of the gastrointestinal membrane, and could offer relief to patients suffering from inflammatory disorders such as Crohn's disease and ulcerative colitis. Previous trials in animals have demonstrated that the activation of cannabinoid receptors in the gastrointestinal tract protects the body from inflammation and modulates gastric secretions and intestinal motility, among other functions.
Cannabis Helps Ulcers And Crohn's Disease
British Nursing News, 23rd March 2006
Researchers claim that cannabis may help combat problems such as intestinal ulcers and Crohn's disease.
The researchers said they found the drug helped the surface cells of the bowel survive in laboratory experiments.
Drugs expert Dr Karen Wright, of Bath University, said: "That means that cannabinoids might well promote wound healing in patients with Crohn's disease and ulcerative colitis.
"We don't know how they do this but they are probably promoting the closure of the wound”.
She said the team were planning a clinical trial.
Bowel Study Backs Cannabis Drugs
BBCi, 1st August 2005
Patients with inflammatory bowel disease may benefit from cannabis-based drugs, UK scientists believe. The Bath University team found people with the gut disorder had an abundant number of a type of cannabinoid receptors in their body.
They believe this is part of the body's attempt to dampen down the inflammation and that giving a drug that binds to these receptors could boost this. Their findings appear in the journal Gastroenterology.
When people have Crohn's disease or ulcerative colitis - collectively known as inflammatory bowel disease or IBD - their immune system goes into overdrive, producing inflammation in different areas of the digestive tract.
This causes symptoms such as pain and urgent diarrhoea.
Anecdotally, people with IBD who have been users of cannabis have reported that their symptoms get better when they use the drug.
" These initial results look extremely promising and exciting." - Dr Derek Scott from Aberdeen University
Dr Karen Wright and colleagues examined gut samples from healthy people and IBD patients and looked for the presence of two receptors known to react to natural cannabis-like compounds produced by the body.
Both the patients and the healthy people had similar numbers of CB1 receptors in their gut. However, the IBD patients had far greater numbers of CB2 receptors.
The normal job of CB1 and CB2 receptors is to switch immune responses on or off. CB1 receptors also help to promote wound healing in the lining of the gut.
Dr Wright said: "This gives us the first evidence that very selective cannabis-derived treatments may be useful as future therapeutic strategies in the treatment of Crohn's and ulcerative colitis.
"This is because some extracts from cannabis, known as cannabinoids, closely resemble molecules that occur naturally in our body, and by developing treatments that target this system, we can help the body recover from some of the effects of these diseases."
She said that the psychoactive effects and the legal implications associated with herbal cannabis use made it unsuitable as a treatment.
However, it might be possible to make a synthetic cannabis-like drug that has all of the therapeutic benefits and none of the other actions of cannabis.
"Targeting drug development to components of the in-built cannabinoid system could be the way forward," she said.
Dr Derek Scott, a researcher in Biomedical Sciences at Aberdeen University, said: "These initial results look extremely promising and exciting.
"However, further work is required so that we can better understand exactly how the signalling pathways controlled by cannabinoid receptors might be targeted in IBD patients, and whether there might be any side-effects."
Cannabis-based medicines are already used for multiple sclerosis in some countries.
Dr John Zycheck, from the Peninsula Medical School in Plymouth, which has been granted £2 million to study these drugs for MS, said: "There is no reason why clinical studies could not be undertaken at a fairly early stage because we are already testing cannabinoids for a variety of different conditions.
"Cannabinoids do have an effect on the gut. It slows gut transit. We see it in our MS patients."
He said more work was needed to check whether these drugs would reduce inflammation and to work out a dose that was strong enough but not toxic.
Dr George Kunos from the US National Institutes of Health said an alternative approach could involve testing compounds that amplify the action of the body's natural cannabinoids by blocking their normal destruction in the gut.
He said animal studies suggested compounds that block the enzyme fatty acid amidohydrolase (FAAH) do this.
Dr John Bennett, Chairman of Core, a national gut and liver disorders charity, said: "I would not want any patient to think that a cannabis-based treatment for IBD is around the corner. Much more work is needed."
Endocannabinoids and the gastrointestinal tract: what are the key questions?
MARIJUANA AND IRRITABLE BOWEL SYNDROME (IBS) (anecdotal)
Tens of millions of people suffer from irritable bowel syndrome (IBS), an enigmatic problem with no known cause and no effective remedy. Sometimes referred to as spastic colon, it affects 10% to 20% of otherwise healthy adults, most of them women. In the United States it accounts for as many as 3.5 million visits to physicians and 2.2 million prescriptions each year. The symptoms include intermittent lower abdominal cramps and bloating accompanied by spells of diarrhea, sometimes alternating with constipation. The abdominal pain generally subsides after a bowel movement or after passing gas, but there is excessive mucus in the stool, and patients often feel that the rectum is not fully emptied. Since IBS is easily confused with other diseases, including Crohn’s disease, ulcerative colitis, diverticula disease, and colorectal cancer, it is important for a person with these symptoms to consult a physician. The most common dietary recommendation is fiber to increase the stool’s bulk and speed it through the gastrointestinal tract. Drug therapy is often not very useful; the drugs most commonly used are anticholinergics and antispasmodics such as Bentyl (dicyclomine) and Imodium (loperamide).
The following account is by a woman who has found marijuana more useful than any prescribed drug.
My name is Christine, and I’m thirty-four years old. I live in the San Francisco Bay area and work as director of information systems for a large labor union. I have a college education and I’m a single mother of two lovely and bright children. I used marijuana recreationally in high school, stopped using it completely when I was 20, and began to use it again on rare occasions recreationally about a year ago. I don’t smoke, drink, or take any other non-prescription drugs.
In 1994 I was diagnosed with irritable bowel syndrome (IBS). My bouts with the disease normally come within thirty minutes of eating. I experience severe cramping, nausea, and diarrhea. Whenever I eat I have to keep track of where the nearest bathroom is just in case. The diagnosis is very frustrating because it basically means that my gastroenterologist cannot find anything to account for my symptoms. I have had a regular workup including a physical exam, flexible sigmoidoscopy, colonoscopy, upper GI with small bowel follow-through, and a month-long bland diet with a phase-in of different foods. None of these tests has turned up any physiological problem that would explain my symptoms. I had as many bouts with IBS on a bland diet as I had eating any other foods.
I was given a prescription for Bentyl (dicyclomine), which slows down the digestive tract so that food doesn’t process through so quickly. The problem is that my bouts with IBS appear to be random, and by the time the Bentyl is in my system I’m already suffering greatly. I found Bentyl to be ineffective unless I took it regularly, which I wasn’t willing to do because it wasn’t that helpful to me and I didn’t like the side effects.
I first tried using marijuana for my IBS about six months ago and found that a few puffs on a joint would give me immediate relief from both the urgent diarrhea and the nausea. I got the idea when my mom was dying of cancer and I was trying to get her to use it for her nausea. I have been trying to find a way to use marijuana immediately at the onset of nausea and cramps, but since it is illegal without a doctor’s recommendation [in California], the situation is difficult. I don’t want to be arrested for using it in public.
I usually pay $80 to $200 an ounce for marijuana. Normally I smoke it in a joint, a pipe, or a water pipe. A water pipe delivers the most cool smoke, so there is less coughing. Ice in the water makes a big difference. I have also tried to eat marijuana when I can get good and fresh buds. To me it tastes like dried basil. Because of my IBS symptoms, eating it isn’t all that appetizing.
I’ve never been arrested for marijuana use or had any problems from using it either recreationally or medicinally.
I hope this information is helpful to somebody. Please let me know if there is any further information you think would be helpful. I would like my last name to be kept private. My first name and e-mail address ([email protected]) are fine to put on your web site.
Shortly after we posted the above clinical account, Christine received the following e-mail from Sammy:
I was so pleased to see someone else with this problem who has been able to treat himself successfully with cannabis. In fact, I don’t go to bed at night without a joint tucked in my night table drawer. I usually get attacks in the early morning and find if I can get myself to the bathroom with a joint and a lighter, I can ease through the attack (which would otherwise put me to bed for a day or so) and be able to fall back to sleep and wake up able to go to work. Nothing else has been as effective, has as few side effects, works as quickly when I need it, etc.
Thanks for letting me share with you...
Here’s to a healthy and happy New Year ... and to the Gov’t and FDA getting some common sense!
Marijuana and Crohn's Disease (anecdotal)
by Marilyn Loskot
My illness began when I was quite young. The symptoms were attacks of intermittent pain in my left abdominal area. My parents were very concerned about these attacks. During one severe attack they took me for an emergency visit to the hospital thinking I was having an appendicitis attack. The doctor couldn’t figure out what was causing the pain. I just had to learn to live with it until 1969. During one especially painful bout of intestinal pain and severe diarrhea I went to see my doctor. His diagnosis was ulcerative colitis. He prescribed Azulfidine and Gantrisin. These drugs helped some but the spasms and pain continued. During this painful period I began experimenting with the use of marihuana to ease the intestinal spasms. It worked better than the prescribed drugs. I therefore discontinued both of the prescribed drugs. I only had flare-ups when I was unable to find a regular supply of medicinal marihuana.
During 1972 we moved to Omaha and I began a new job that was stressful. I also could not find a source for my medicinal marihuana. During this time one of my favorite nephews had a painful death from a tumor on his brain stem. About three weeks after I returned home to Omaha I believe the stress triggered a severe attack of my colitis. I became so ill I began vomiting and had bloody diarrhea. I also began losing weight rapidly. My doctor became so concerned that he put me into the research facility and hospital at the University of Nebraska. They performed a battery of tests including a colonoscopy and biopsy of my intestines. The experts there diagnosed my illness as Crohn’s disease. After I was stabilized in the hospital I was released and given prescriptions for Azulfidine, steroids, and pain medications. I never did find a source for my medical marihuana and existed on pain pills and mood elevators (Sinequan). These pills helped me deal with the pain and spasms but did nothing to decrease the frequency of pain causing spasms. I wasn’t able to find a source of medicinal marihuana until 1975 when we moved to San Diego.
Using a regular supply of medicinal marihuana I was able to discontinue all of the prescriptions that had allowed me to just survive with the pain in Omaha. I felt so good that I obtained a new job as a computer programmer at a major bank. I moved to northern California in 1981 and have had very few symptoms. I had no symptoms serious enough to require a doctor’s care until 1996 when my husband and I were arrested for being at our connection’s house when they were arrested for marihuana. This arrest caused them to search our home and they found our nine baby medicinal marihuana plants growing in a photo-tron in our closet. This closet set-up provided us with about three ounces every four months. This amount was not enough to allow treatment of my husband’s paraplegia spasms and my Crohn’s disease. So, we had to buy just two or three extra ounces per year. This buying from the black market resulted in the arrest I mentioned earlier. Because of this arrest my husband and I are denied the legal use of our doctor-recommended medical marihuana by a draconian judge until the year 2000. So, until then my husband and I must resort to addictive narcotics and mood drugs, prescribed chemicals to dull our pain and spasms. When will the government realize the value of these natural herbs?
Cannabis-based drugs could offer new hope for inflammatory bowel disease patients
Article Date: 04 Aug 2005
Researchers investigating anecdotal evidence that cannabis relieves some of the symptoms of inflammatory bowel disease (IBD) have discovered a potential new target for cannabis-derived drugs for treatment of the disease.
This finding, published in the journal Gastroenterology today (Monday 1 August), could bring new hope for the UK's 90,000 - 180,000 sufferers of diseases like Crohn's and ulcerative colitis1 with the possibility that cannabis-derived drugs may help to heal the gut lining, which is damaged during the course of disease.
Both Crohn's and ulcerative colitis - often referred to under the umbrella term of IBD - cause patients' immune systems to go into overdrive, producing inflammation in different areas of the gastrointestinal tract.
This inflammation can cause pain, urgent diarrhoea, severe tiredness and loss of weight, and is most commonly diagnosed in young adults of both sexes between the ages of 15 and 25.
Patients with IBD who are also users of cannabis often report that their symptoms are alleviated following cannabis use, suggesting that the gut is able to respond to some of the molecules found in cannabis.
Investigating this phenomenon, researchers from the University of Bath worked with colleagues at the Royal United Hospital in Bath to look at the interaction of cannabis with specific molecules, known as receptors, found on the surface of cells in the gut.
Examining gut samples from healthy people and IBD patients, the researchers looked at two specific receptors, called CB1 and CB2, which are known to be activated by the presence of molecules found in cannabis.
They discovered that whilst CB1 is present in healthy people, the presence of CB2 increases in IBD patients as their disease progresses.
The researchers believe that the presence of CB2 receptor only during the disease-state may be linked to its known role in suppression of the immune system. In other words, it is part of the body's natural mechanisms that attempt to restore the normal healthy state of the gut.
If so, this makes it an ideal candidate for the development of new cannabis-derived drugs to help IBD patients. They also found that the CB1 receptor helps to promote wound healing in the lining of the gut.
"This gives us the first evidence that very selective cannabis-derived treatments may be useful as future therapeutic strategies in the treatment of Crohn's and ulcerative colitis," said Dr Karen Wright from the University's Department of Pharmacy and Pharmacology.
"This is because some extracts from cannabis, known as cannabinoids, closely resemble molecules that occur naturally in our body, and by developing treatments that target this system, we can help the body recover from some of the effects of these diseases."
Ordinarily, CB1 and CB2 have the task of recognising and binding to a family of substances called "endocannabinoids" that occur naturally in our bodies. Once these receptors have detected the presence of specific molecules in their surrounding environment, a chain of biochemical signals is activated which culminates in switching immune responses on or off - depending on what their function is.
"The normal job of the CB1 and CB2 receptors is to help moderate diverse responses throughout the body, but their presence in the gut means that they could be useful targets for the development of cannabis-derived drugs for controlling the progression of IBD," said Dr Wright.
"The research shows that whilst cannabis use may have some benefits for patients with IBD, the psychoactive effects and the legal implications associated with herbal cannabis use make it unsuitable as a treatment. Targeting drug development to components of the in-built cannabinoid system could be the way forward."
Cannabis-based medicines that help alleviate the pain endured by Multiple Sclerosis patients have already been given a licence for use in Canada, and Salisbury-based GW Pharmaceuticals is pioneering many of the advances in this field.
The research was funded by the Wellcome Trust and an NHS Research Grant.
Case studies of people with colitis or Crohn's are available from National Association for Colitis and Crohn's Disease on +44 (0)1727 830038.
1Figures from the National Association for Colitis and Crohn's Disease. There is no national database of people with Crohn's or Colitis - the figures are taken from estimates published by the British Society for Gastroenterology in 2004.
Inflammatory Bowel Disease
Inflammatory Bowel Disease (IBD) is an umbrella term referring to two chronic diseases that cause inflammation of the intestines: ulcerative colitis (UC) and Crohn's disease (CD).
Between 30,000 and 60,000 people in the UK live with CD. Between 3,000 and 6,000 new cases are diagnosed each year.
In 1996, a study from South Glamorgan reported a doubling of the number of children diagnosed with CD between 1983 and 1993
In 1999 a study of children in Scotland has reported a 50% increase over 10 years in the incidence of CD.
CD can affect anywhere from the mouth to the rectum but most commonly affects the small intestine.
It causes inflammation, deep ulcers and scarring to the wall of the intestine and often occurs in patches with healthy tissue in between. There is no cure for CD at present.
The main symptoms are pain, urgent diarrhoea, severe tiredness and loss of weight.
CD is quite often associated with other inflammatory conditions affecting the joints, skin and eyes. Most patients will be treated with drugs, including steroids, to reduce inflammation or by means of special liquid feeds to rest the bowel. Surgery may be required to remove narrowed or damaged parts of the intestine.
The condition is named after Dr Burril Crohn, one of the three doctors who first identified the disease in 1932. The cause of CD has not yet been identified.
Between 60,000 and 120,000 people in the United Kingdom live with UC
Between 6,000 and 12,000 new cases are diagnosed each year.
Ulcerative Colitis affects men and women equally.
The number of new cases each year has not risen recently, but is not decreasing.
Ulcerative Colitis affects the colon (large intestine) or rectum. Inflammation and ulcers develop on the inside lining of the colon resulting in pain, urgent and bloody diarrhoea, and continual tiredness.
There is no cure for Ulcerative Colitis at present.
The condition varies as to how much of the colon is affected and the severity of the symptoms also fluctuates unpredictably over time. Patients are likely to experience flare-ups in between intervals of reduced symptoms or remission.
Most patients will be treated with drugs, including steroids, to control or reduce the inflammation. Some people need surgery to remove the affected part of the colon, if their symptoms do not respond to treatment with drugs.
The cause of UC has not yet been identified. The University of Bath is one of the UK's leading universities, with an international reputation for quality research and teaching. In 17 subject areas the University of Bath is rated in the top ten in the country.
View a full list of the University's press releases: bath.ac.uk/news/releases
Cannabidiol, extracted from Cannabis sativa, selectively inhibits inflammatory hypermotility in mice
Capasso R, Borrelli F, Aviello G, Romano B, Scalisi C, Capasso F, Izzo AA
1Department of Experimental Pharmacology, University of Naples Federico II and Endocannabinoid Research Group, Naples, Italy.
Background and purpose:Cannabidiol is a Cannabis-derived non-psychotropic compound that exerts a plethora of pharmacological actions, including anti-inflammatory, neuroprotective and antitumour effects, with potential therapeutic interest. However, the actions of cannabidiol in the digestive tract are largely unexplored. In the present study, we investigated the effect of cannabidiol on intestinal motility in normal (control) mice and in mice with intestinal inflammation.Experimental approach:Motility in vivo was measured by evaluating the distribution of an orally administered fluorescent marker along the small intestine; intestinal inflammation was induced by the irritant croton oil; contractility in vitro was evaluated by stimulating the isolated ileum, in an organ bath, with ACh.Key results:In vivo, cannabidiol did not affect motility in control mice, but normalized croton oil-induced hypermotility. The inhibitory effect of cannabidiol was counteracted by the cannabinoid CB(1) receptor antagonist rimonabant, but not by the cannabinoid CB(2) receptor antagonist SR144528 (N-[-1S-endo-1,3,3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide), by the opioid receptor antagonist naloxone or by the alpha(2)-adrenergic antagonist yohimbine. Cannabidiol did not reduce motility in animals treated with the fatty acid amide hydrolase (FAAH) inhibitor N-arachidonoyl-5-hydroxytryptamine, whereas loperamide was still effective. In vitro, cannabidiol inhibited ACh-induced contractions in the isolated ileum from both control and croton oil-treated mice.Conclusions and implications:Cannabidiol selectively reduces croton oil-induced hypermotility in mice in vivo and this effect involves cannabinoid CB(1) receptors and FAAH. In view of its low toxicity in humans, cannabidiol may represent a good candidate to normalize motility in patients with inflammatory bowel disease.British Journal of Pharmacology (2008) 154, 1001-1008; doi:10.1038/bjp.2008.177; published online 12 May 2008.
Published 30 June 2008 in Br J Pharmacol, 154(5): 1001-8.
Full-text of this article is available online (may require subscription)
Cannabinoids and gastrointestinal motility: animal and human studies
|Author(s)||Aviello G, Romano B, Izzo AA|
|Institution||Department of Experimental Pharmacology and Endocannabinoid Research Group, University of Naples Federico II, Naples, Italy.|
|Source||Eur Rev Med Pharmacol Sci 2008 Aug.:81-93.|
|Abstract||The plant Cannabis has been known for centuries to be beneficial in a variety of gastrointestinal diseases, including emesis, diarrhea, inflammatory bowel disease and intestinal pain. delta9-tetrahydrocannabinol, the main psychotropic component of Cannabis, acts via at least two types of cannabinoid receptors, named CB1 and CB2 receptors. CB1 receptors are located primarily on central and peripheral neurons (including the enteric nervous system) where they modulate neurotransmitter release, whereas CB2 receptors are concerned with immune function, inflammation and pain. The discovery of endogenous ligands [i.e. anandamide and 2-arachidonoyl glycerol (2-AG)] for these receptors indicates the presence of a functional endogenous cannabinoid system in the gastrointestinal tract. Anatomical and functional evidence suggests the presence of CB1 receptors in the myenteric plexus, which are associated with cholinergic neurons in a variety of species, including in humans. Activation of prejunctional CB1 receptors reduces excitatory enteric transmission (mainly cholinergic transmission) in different regions of the gastrointestinal tract. Consistently, in vivo studies have shown that cannabinoids reduce gastrointestinal transit in rodents through activation of CB1, but not CB2, receptors. However, in pathophysiological states, both CB1 and CB2 receptors could reduce the increase of intestinal motility induced by inflammatory stimuli. Cannabinoids also reduce gastrointestinal motility in randomized clinical trials. Overall, modulation of the gut endogenous cannabinoid system may provide a useful therapeutic target for disorders of gastrointestinal motility.|
|Pub Type(s)||Journal Article|
Research Support, Non-U.S. Gov't
Cannabinoids and intestinal motility: welcome to CB2 receptors
Copyright 2004, Nature Publishing Group
Cannabinoids and intestinal motility: welcome to CB2 receptors
Angelo A Izzo1*
1Department of Experimental Pharmacology, University of Naples Federico II, via D Montesano 49, 80131 Naples, Italy
Received April 16, 2004; Accepted May 21, 2004.
Δ9-Tetrahydrocannabinol (the active ingredient of marijuana), as well as endogenous and synthetic cannabinoids, exert many biological functions by activating two types of cannabinoid receptors, CB1 receptors (expressed by central and peripheral neurons) and CB2 receptors (that occur mainly in immune cells). Convincing evidence has accumulated in recent years that cannabinoids inhibit gastric and intestinal motility through activation of enteric CB1 receptors. However, a report in this issue of British Journal of Pharmacology has highlighted the possibility that CB2 receptors in the rat intestine could contribute to reducing the increase of intestinal motility induced by an endotoxic inflammation. By minimizing the adverse psychotropic effects associated with brain cannabinoid receptors, the CB2 receptor represents a new...read more with images
The endogenous cannabinoid system protects against colonic inflammation
Colon pathologies span a wide range of different conditions, including frankly inflammatory bowel diseases (ulcerative colitis and Crohn disease) and so-called...read more with images
Central and peripheral cannabinoid modulation of gastrointestinal transit in physiological states or during the diarrhoea induced by croton oil
Br J Pharmacol. 2000 April; 129(8): 1627–1632.
- We have evaluated the effect of cannabinoid drugs, administered intraperitoneally (i.p.) or intracerebroventricularly (i.c.v.) on upper gastrointestinal transit in control and in croton oil-treated mice.
- The cannabinoid agonists, WIN 55,212-2 (2–239nmolmouse−1) and cannabinol (24–4027nmolmouse−1), decreased while the CB1 antagonist SR141716A (2–539nmolmouse−1) increased transit in control mice. WIN 55,212-2, cannabinol and SR141716A had lower ED50 values when administered i.c.v., than when administered i.p. The CB2 antagonist SR144528 (52nmol mouse−1, i.p.) was without effect.
- During croton oil (0.01mlmouse−1, p.o.)-induced diarrhoea, the ED50 values of i.p.-injected WIN 55,212-2 and cannabinol (but not SR141716A) were significantly decreased (compared to control mice). However, the ED50 values of WIN 55,212-2 were similar after i.p. or i.c.v. administration.
- The inhibitory effects of WIN 55,212-2 and cannabinol were counteracted by SR141716A (16nmolmouse−1, i.p.) but not by SR144528 (52nmolmouse−1, i.p.) both in control and croton-oil treated mice.
- Ganglionic blockade with hexamethonium (69nmolmouse−1, i.p.) did not modify the inhibitory effect of i.p.-injected cannabinoid agonists either in control or in croton-oil treated mice.
- The lower ED50 values of cannabinoid drugs after i.c.v. administration suggest a central (CB1) site of action. However, a peripheral site of action is suggested by the lack of effect of hexamethonium. In addition, croton oil-induced diarrhoea enhances the effect of cannabinoid agonists by a peripheral mechanism.
Understanding of the mechanism by which Δ9-THC exerts its pharmacological actions has seen considerable progress in the last ten years following the discovery of two distinct cannabinoid receptors, named CB1, (expressed mainly by central and peripheral neurons) and CB2 (that occur mainly in immune cells)...read more with graphs
Anti-inflammatory compound from cannabis found in herbs
24 June 2008
A compound found in cannabis as well as in herbs such as basil and oregano could help to treat inflammatory bowel diseases and arthritis, Swiss scientists believe.
(E)-beta-caryophyllene (BCP) is an aromatic sesquiterpene that has used for many years as a food additive because of its peppery flavour. The researchers now say that it interacts selectively with one of two cannabinoid receptors, CB2, blocking the chemical signals that lead to inflammation without triggering cannabis's mood-altering effects.
Many cannabinoids bind to the CB2 receptor, but few target it selectively. Most also interact with CB1, which is responsible for cannabis' psychoactive properties. CB1 is found in brain tissue, whereas CB2 is found only in cells elsewhere in the body.
Model of the interaction of BCP with the CB2 receptor
© Gertsch et al, PNAS
The compound is the only product identified in nature that activates CB2 selectively. 'There are many compounds that have been designed synthetically that are CB2 selective, but they are made in the lab,' says Jürg Gertsch, who led the study at the Swiss Federal Institute of Technology.
According to Gretsch, BCP is potent enough to have an impact at normal dietary levels. Herbs such as basil and oregano contain large amounts of the compound, he says, suggesting that the Mediterranean diet may protect against Crohn's disease and other inflammatory bowel diseases. 'If somebody eats a lot of herbs containing essential oils then it's possible they could get enough to reach a therapeutic dose,' Gertsch says.
The team screened a whole library of natural products for cannabinoid activity, which led finally to fractionation of Cannibis sativa essential oil and identification of BCP as the active component. They then tested the compound by using it to treat mice with swollen paws and found that in around 70 per cent of cases, small doses of BCP were enough to make the inflammation subside. BCP may also account for the for the anti-inflammatory properties of copaiba oil, an essential oil prescribed by doctors and healers in Brazil, which contains large quantities of the compound.
Birgit Kraft, who studies the therapeutic effects of marijuana at the Medical University of Vienna, says selective CB2 agonists are keenly sought after by clinicians, as they may be candidates for treatment of rheumatoid arthritis, as well as bowel disease.
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J Gertsch et al, PNAS Early Edition, 2008, DOI: 10.1073/pnas.0803601105.
Intestinal obstruction by an unusual foreign body
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- LIPIN RJ, HARA M. Bezoars (diopyrobezoars). Am J Surg. 1962 Apr;103:494–497. 
- Weinerman R, Weinerman B, McIntyre DF, Hillsman JA, Rogers AG. Ball-value obstruction of terminal ileum of long duration by a rare phytobezoar. JAMA. 1967 Jan 23;199(4):274–276. 
- Carter DC, Macleod DA. Obturation obstruction of the small intestine. J R Coll Surg Edinb. 1970 Jan;15(1):13–20. 
- Vernon JK. Small bowel obstruction secondary to repane ingestion. Report of a case and review of the literature. Arch Surg. 1969 Jun;98(6):717–719. 
- Deitel M. Successful use of the Miller-Abbott tube. Can J Surg. 1967 Apr;10(2):245–257. [PubMed]
- Articles from Canadian Medical Association Journal are provided here courtesy of Canadian Medical Association
Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa, is protective in a murine model of colitis
Borrelli F, Aviello G, Romano B, Orlando P, Capasso R, Maiello F, Guadagno F, Petrosino S, Capasso F, Di Marzo V, Izzo AA
J Mol Med 2009 Nov; 87(11):1111-21
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.
The endogenous cannabinoid system protects against colonic inflammation
Colon pathologies span a wide range of different conditions, including frankly inflammatory bowel diseases (ulcerative colitis and Crohn disease) and so-called functional bowel diseases (e.g., irritable bowel syndrome), and represent an important and widespread health problem in modern society... read full text with graphs
Cannabinoids in intestinal inflammation and cancer
Pharmacol Res. 2009 Aug;60(2):117-25. Epub 2009 Mar 18.
Department of Experimental Pharmacology, University of Naples Federico II and Endocannabinoid Research Group, Naples, Italy. [email protected]
Emerging evidence suggests that cannabinoids may exert beneficial effects in intestinal inflammation and cancer. Adaptive changes of the endocannabinoid system have been observed in intestinal biopsies from patients with inflammatory bowel disease and colon cancer. Studies on epithelial cells have shown that cannabinoids exert antiproliferative, antimetastatic and apoptotic effects as well as reducing cytokine release and promoting wound healing. In vivo, cannabinoids - via direct or indirect activation of CB(1) and/or CB(2) receptors - exert protective effects in well-established models of intestinal inflammation and colon cancer. Pharmacological elevation of endocannabinoid levels may be a promising strategy to counteract intestinal inflammation and colon cancer.
PMID: 19442536 [PubMed - indexed for MEDLINE]
Synthetic THC Eases Stomach Cramping, Study Says
October 26, 2006 - Rochester, MN, USA
Rochester, MN: Cannabinoids reduce stomach cramping and may play a role in moderating various gastrointestinal (GI) disorders, according to clinical trial data presented this week at the 71st Annual Scientific Meeting of the American College of Gastroenterology.
Investigators at the Mayo Clinic in Minnesota assessed the efficacy of a single dose of dronabinol (synthetic THC) on colonic motility in 52 volunteers participating in a double-blind, placebo-controlled trial. Researchers reported that THC relaxes the colon and eases post-eating contractions and cramping compared to placebo.
Investigators said that these effects were more prominent in women volunteers than men.
"The potential for cannabinoids to modulate colonic motor function in disease deserves a further look," they concluded.
Survey data reported last fall in O'Shaughnessy's: The Journal of Cannabis in Clinical Practice found that Crohn's disease patients experience subjective benefits from cannabis, including pain relief and increased appetite.
Researchers in the United Kingdom also reported last year that cannabinoids promote healing in the gastrointestinal membrane, and may provide therapeutic relief to patients with irritable bowel syndrome.
More recently, investigators from Germany's Johannes Gutenberg University reported this spring in the Journal of Endocrinological Investigation that the "endocannabinoid system may represent a new promising therapeutic target against different GI disorders, including inflammatory bowel diseases, functional bowel diseases, and secretion and motility disorders."
Gastrointestinal disorders afflict more than one in five Americans, particularly women.
For more information, please contact Paul Armentano, NORML Senior Policy Analyst, at (202) 483-5500. Additional information on cannabinoids and GI disorders is available in NORML's new report, "Emerging Clinical Applications for Cannabis and Cannabinoids," available online at: http://www,rg//index.cfm?Group_ID=7002.
Br J Pharmacol. 2000 March; 129(5): 984–990.
- The effect of cannabinoid drugs on peristalsis in the guinea-pig ileum was studied. Peristalsis was induced by delivering fluid into the oral end of an isolated intestinal segment. Longitudinal muscle reflex contraction, threshold pressure and threshold volume to trigger peristalsis, compliance of the intestinal wall during the preparatory phase (a reflection of the resistance of the wall to distension) and maximal ejection pressure during the emptying phase of peristalsis were measured.
- The cannabinoid agonists WIN 55,212-2 (0.3–300nM) and CP55,940 (0.3–300nM) significantly decreased longitudinal muscle reflex contraction, compliance and maximal ejection pressure, while increased threshold pressure and volume to elicit peristalsis. These effects were not modified by the opioid antagonist naloxone (1μM) and by the α-adrenoceptor antagonist phentolamine (1μM).
- The inhibitory effect of both WIN 55,212-2 and CP55,940 on intestinal peristalsis was antagonized by the cannabinoid CB1 receptor antagonist SR141716A (0.1μM), but not by the cannabinoid CB2 receptor antagonist SR144528 (0.1μM).
- In absence of other drugs, the CB1 receptor antagonists SR141716A (0.01–1μM) and AM281 (0.01–1μM) slightly (approximatively 20%) but significantly increased maximal ejection pressure during the empty phase of peristalsis without modifying longitudinal muscle reflex contraction, threshold pressure, threshold volume to trigger peristalsis and compliance.
- It is concluded that activation of CB1 receptors reduces peristalsis efficiency in the isolated guinea-pig, and that the emptying phase of peristalsis could be tonically inhibited by the endogenous cannabinoid system.
The guinea-pig....read more with graphs and ref...