GBR: Cannabis May Soothe Inflamed Bowels

Buzzby · Aug 2, 2005

Cannabis May Soothe Inflamed Bowels
Gaia Vince | New Scientist | 08/01/2005

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.

Repair trigger

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.

Excess cells

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.

SkyTripper · Aug 2, 2005

If marijuana would just get legalized and approved by the FDA......

I can see the tv commercials around dinnertime.....

"When it hurts to shiit.....take another hit!"
MARIJUANA....."IT DOES YOUR COLON GOOD"

"Ask your doctor for a free sample now."

teufelfisch · Aug 2, 2005

Wow, great article!

I found the information about the receptors particularly interesting. We've known for a long time that CB1 receptors are in the brain. Now that we've found them in other parts of the body, could lead to evidence that marijuana provides a holistic sort of therapy.

Although no one knows the purpose of CB2 receptors, it's suspected they play a role in the immune system, since they're mostly located around the spleen.

Higher Logic · Aug 2, 2005

Check out this thread on IBS, Chron's, and MS. Here's an excerpt:

Just another study done by the University of Naples (Italy):

"∆9-THC, as well as endogenous and synthetic cannabinoids, exert many biological functions by activating two types of cannabinoid receptors, CB1 and CB2 receptors. CB1 receptors have been detected on enteric nerves, and pharmacological effects of their activation include gastroprotection, reduction of gastric and intestinal motility and reduction of intestinal secretion. The digestive tract also contains endogenous cannabinoids (the endocannabinoids anandamide and 2-aracidonylglycerol) and mechanisms for endocannabinoid inactivation (endocannabinoids uptake and enzymatic degradation). Cannabinoid receptors, endocannabinoids and the proteins involved in endocannabinoids inactivation are collectively referred as the ‘endogenous cannabinoid system’. A pharmacological modulation of the endogenous cannabinoid system could provide new therapeutics for the treatment of a number of gastrointestinal diseases, including nausea and vomiting, gastric ulcers, irritable bowel syndrome, Crohn’s disease, secretory diarrhoea, paralytic ileus and gastroesophageal reflux disease. Some cannabinoids are already in use clinically, for example, nabilone and ∆9-tetrahydrocannabinol are used as antiemetics."

Anandamide is a naturally occurring endogenous cannabinoid chemical compound of the mammal brain which is released in response to pain. Anandamide may play important roles in the regulation of mood, memory, appetite, and pain perception.

Nabilone is a synthetic cannabinoid used in the treatment of nausea and vomiting associated with cancer chemotherapy, as well as multiple sclerosis. Nabilone has anxiolytic properties (relieves anxiety), and studies done by Fabre & McLendon concluded that patients taking nabilone over a 28-day-period demonstrated dramatic improvements. The great thinga bout nabilone, it doesn't mimic THC so no "altered" states are noted, as well there are only three side effects (compared to prescription anti-anxiety drugs) which are dry mouth, drowsiness, and dry eyes; something most of us have experienced from smoked cannabis.

For more information on the therapeutic aspects of cannabis and cannabinoids (inlcudes references to nabilone), see the following article published by the The British Journal of Psychiatry.

For more information on gastrointestinal diseases and cannabis, see the following 12-page PDF document.

Also, something called Clinical Endocannabinoid Deficiency (CECD) is a concept that might explain the therapeutic benefits of cannabis in migraines, fibromyalgia, irritable bowel syndrome, and other treatment-resistant conditions; for more information on CECD, see the following 9-page PDF document.

Irritable Bowel Syndrome (IBS)
IBS is the most common condition that a physician faces in the GI clinic. It is a functional bowel disorder associated with abdominal discomfort or pain and altered bowel habits. Abnormal intestinal motility, including increased contractility and accelerated transit, is often associated with many IBS symptons. Hence, antispasmodics and drugs that decrease intestinal transit are currently used in treatement of IBS.

Cannabinoid receptor agonists affect isolated intestinal segments in a manner that resembles the action of opioid receptor agonists. Thus, a number of cannabinoid receptor agonists (via CB1 activation) have been shown to reduce or inhibit excitatory transmission, neural acetylcholine release and peristalsis efficiency in isolated intestinal segments. A functional evidence for the presence of prejunctional CB1 in the human isolated ileum and colon, through which the cannabinoid receptor agonist WIN55,212-2 inhibited electrically-evoked contractile responses, has also been demonstrated.

Consistent with these in vitro studies, cannabinoid receptor agonists reduce gastric, small intestinal and colonic motility in rodents, an effect which is due, at least in part, to activation of peripheral (enteric) CB1 receptors. Notably, McCaullum and colleagues have found delta9-THC to delay gastric emptying in humans.

A recent study reports strong evidence for the existence of a local endocannabinoid tone controlling propulsion in the mouse colon in vivo. The evidence is based on the findings that:

o Unusually high amounts of endocannabinoids are present in the mouse colon
o A stimulatory action on colonic propulsion occurs after selective blockade of CB1 receptors with SR141716A
o An inhibitory effect on colonic propulsion occurs after inhibition of endocannabinoid re-uptake with VDM11

These findings open the way to use of non-psychotropic drugs that activate enteric CB1 receptors or selectively reduce endocannabinoid inactivation for the treatment of the motility disorders associated with IBS.

"There is anecdotal evidence for the therapeutic benefit of cannabinoids in a variety of human disease conditions, that spans over many centuries. Recently, however, in-depth research efforts have begun to document the biological mechanism involved. In addition, it is becoming clear that a pharmacological manipulation of the endogeneous cannabinoid system could have important therapeutic applications, including for the pathologies of the digestive system."

That's the only problem I have with all this research, I don't think it benefits the legalization efforts, as it's just another way for man to exploit the power of natural substances that could be benefiting a lot of people right now, but instead require lengthy periods of time and clinical research and studies. End of the day, cannabis has thousands of benefits for a wide range of diseases including emesis, irritable bowel syndrome (IBS), chron's disease, gastroesophageal reflux disease (GERD), paralytic ileus, secretory diarrhoea, and gastric ulcers.

And this...

Although the use of cannabinoids as antiemetics (anti-nausea) is well-established, with Dronabinol available to stimulate appetite and counter effects of cancer chemotherapy, the effect of cannabinoids on disorders of the gut has not been extensively studied. However the current state of knowledge of the biochemistry of cannabinoids is increasing at an exponential rate and, with discoveries of cannabinoid receptors in unexpected areas of the body, new potential research/treatment avenues are appearing at an increasing rate.

Grinspoon reports anecdotal use of cannabis to control bowel movements in multiple sclerosis, and relief from the symptoms of Crohn"s disease. Mikuriya records irritable bowel syndrome, as well as other inflammatory gastrointestinal conditions (principally among AIDS patients), as one of a wide variety of conditions for which cannabis has been prescribed or recommended for therapeutic use in California. There are no clinical trials currently published, and consequently use for the treatment of irritable bowel syndrome would represent at best an experimental therapy.

However, there does appear to be some scientific support for any claimed therapeutic benefits from the research literature concerning the actions and metabolism of cannabinoids and cannabinoid receptors. The wall of the intestine is composed of a type of muscle known as "smooth muscle", also found lining the walls of arteries and in other involuntary functions.

Rosell et al first demonstrated that cannabinoids inhibit contractions of the small intestine in the rat. Pertwee et al established the presence of cannabinoid (CB1) receptors within the guinea-pig intestine and Kazuhisa et al established the presence of enzymes break down anandamide (the endogenous cannabinoid CB1-agonist) within the small intestine. The smooth muscle-relaxant properties of cannabinoids are so well established that preparations of guinea-pig intestine are routinely used as an in vitro screening tool to test the potency and function of novel cannabinoids.

Shook & Burks found that THC reduced the frequency of intestinal contractions, and reduced the flow of food in the small intestine, without altering basal tone, and concluded that

"...delta 9-THC, delta 9,11-THC, cannabinol and nabilone (but not cannabidiol) exert an inhibitory effect on GI transit and motility in rats".

Cadas et al reported that a gut enzyme (vasoactive intestinal peptide) may regulate the precursor chemical to anandamide (which activates cannabinoid CB1 receptors) and N-palmitoylethanolamine (which activates a CB2-like receptor subtype), suggesting that endogenous cannabinoids may play a role in regulating the activity of the gut.

We are not aware of any controlled studies of medical use of cannabis in the treatment of irritable bowel syndrome, there appears to be sufficient evidence of the potential efficacy of cannabis in reducing intestinal spasms to merit further research into this and related indications. Any symptomatic relief obtained from smoking cannabis would occur far more rapidly than with oral preparations.