Category Archives: Irritable Bowel Syndrome (IBS)

Cannabis use amongst patients with inflammatory bowel disease.

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“Experimental evidence suggests the endogenous cannabinoid system may protect against colonic inflammation, leading to the possibility that activation of this system may have a therapeutic role in inflammatory bowel disease (IBD).

Medicinal use of cannabis for chronic pain and other symptoms has been reported in a number of medical conditions.

We aimed to evaluate cannabis use in patients with IBD…

CONCLUSION:

Cannabis use is common amongst patients with IBD for symptom relief, particularly amongst those with a history of abdominal surgery, chronic abdominal pain and/or a low quality of life index.

The therapeutic benefits of cannabinoid derivatives in IBD may warrant further exploration.”

http://www.ncbi.nlm.nih.gov/pubmed/21795981

Anti-inflammatory cannabinoids in diet: Towards a better understanding of CB(2) receptor action?

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“The endocannabinoid system is an ancient lipid signaling network which in mammals modulates neuronal functions, inflammatory processes, and is involved in the aetiology of certain human lifestyle diseases, such as Crohn’s disease, atherosclerosis and osteoarthritis.

The system is able to downregulate stress-related signals that lead to chronic inflammation and certain types of pain, but it is also involved in causing inflammation-associated symptoms, depending on the physiological context.

The cannabinoid type-2 (CB2) receptor, which unlike the CB1 receptor does not induce central side effects, has been shown to be a promising therapeutic target. While CB1 receptor antagonists/inverse agonists are of therapeutic value, also CB2 receptor ligands including agonists are of pharmacological interest.

 Although the endocannabinoid system is known to be involved in the regulation of energy homoeostasis and metabolism (mainly via CB1 receptors) there was hitherto no direct link between food intake and cannabinoid receptor activation. Our recent finding that beta-caryophyllene, a ubiquitous lipohilic plant natural product, selectively binds to the CB2 receptor and acts as a full agonist is unexpected…

In the case of the dietary natural product beta-caryophyllene, a full CB2 receptor-selective agonist in vitro, potent anti-inflammatory cannabimimetic effects are observed. Intriguingly, the lowest oral dose tested (5 mg/Kg) of this widespread and apparently non-toxic compound, which is also an FDA-approve food additive, was the most effective. Maybe this strengthens the hypothesis that beta-caryophyllene is indeed a dietary cannabinoid, thus inferring that by eating this compound the endocannabinoid system may be modulated in a beneficial way…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633791/

The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity.

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“Crohn’s disease and ulcerative colitis are two major forms of inflammatory bowel diseases (IBD), which are chronic inflammatory disorders of the gastrointestinal tract. These pathologies are currently under investigation to both unravel their etiology and find novel treatments.

Anandamide and 2-arachidonoylglycerol are endogenous bioactive lipids that bind to and activate the cannabinoid receptors, and together with the enzymes responsible for their biosynthesis and degradation [fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL)] constitute the endocannabinoid system (ECS).

The ECS is implicated in gut homeostasis, modulating gastrointestinal motility, visceral sensation, and inflammation, as well as being recently implicated in IBD pathogenesis.

Numerous subsequent studies investigating the effects of cannabinoid agonists and endocannabinoid degradation inhibitors in rodent models of IBD have identified a potential therapeutic role for the ECS.”

http://www.ncbi.nlm.nih.gov/pubmed/22917662

The Cannabinoid 1 Receptor (CNR1) 1359 G/A Polymorphism Modulates Susceptibility to Ulcerative Colitis and the Phenotype in Crohn’s Disease

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“Anecdotal reports suggest that marijuana- or tetrahydrocannabinol-containing products may be effective in alleviating symptoms in patients with ulcerative colitis (UC) and Crohn’s disease (CD). This is supported by recent studies of our group and others suggesting that pharmacological activation of the cannabinoid 1 (CB1) receptor with selective receptor agonists decreases the inflammatory response in various murine models of colonic inflammation…

Recent evidence suggests a crucial role of the endocannabinoid system, including the cannabinoid 1 receptor (CNR1), in intestinal inflammation. We therefore investigated the influence of the CNR1 1359 G/A (p.Thr453Thr; rs1049353) single nucleotide polymorphism (SNP) on disease susceptibility and phenotype in patients with ulcerative colitis (UC) and Crohn’s disease (CD)…

Conclusion

The CNR1 p.Thr453Thr polymorphism appears to modulate UC susceptibility and the CD phenotype. The endocannabinoid system may influence the manifestation of inflammatory bowel diseases, suggesting endocannabinoids as potential target for future therapies.

…our findings provide further evidence that endocannabinoids modulate intestinal inflammation, suggesting that this system could act as a target for future therapeutic interventions.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2829088/

Targeting endocannabinoid degradation protects against experimental colitis in mice: involvement of CB1 and CB2 receptors.

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“The endocannabinoid (EC) system mediates protection against intestinal inflammation. In this study, we investigated the effects of blocking EC degradation or cellular reuptake in experimental colitis in mice…

 In conclusion, drugs targeting EC degradation offer therapeutic potential in the treatment of inflammatory bowel diseases. Furthermore, reduction of FAAH mRNA expression is involved in the pathophysiological response to colitis.”

http://www.ncbi.nlm.nih.gov/pubmed/18493729

The role of fatty acid hydrolase gene variants in inflammatory bowel disease.

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“Recent studies suggest a role for the endocannabinoid system, including fatty acid amide hydrolase (FAAH), in intestinal inflammation.

AIM:

To analyse FAAH expression and the FAAH 385 C/A (p.Pro129Thr; rs324420) single nucleotide polymorphism (SNP) in-patients with Crohn’s disease (CD) and ulcerative colitis (UC).

CONCLUSION:

The FAAH p.Pro129Thr polymorphism may modulate the CD phenotype.”

http://www.ncbi.nlm.nih.gov/pubmed/19053981

Role of cannabinoid receptors and RAGE in inflammatory bowel disease.

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“The endocannabinoid system is involved in many inflammatory diseases, such as Crohn’s disease (CD) and ulcerative colitis (UC). The distribution and expression of cannabinoid receptors 1 (CNR1) and 2 (CNR2) in combination with inflammatory cytokines and RAGE (receptor of advanced glycation end products), which is also overactive in these diseases, in dependency of the extent of inflammation and alteration of the colon barrier is still unclear and needs to be elucidated…

 

CONCLUSION:

We showed that cannabinoid receptors are expressed differentially in inflammatory bowel disease and that the expression seems to be influenced by the underlying disease and by localized inflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/21472688

The pathophysiologic rationale for biological therapies in inflammatory bowel disease.

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“Inflammatory bowel disease is driven by an excessive immune response in the gut wall. This review summarises important new developments in understanding this immune response and the downstream mechanisms of intestinal injury, alongside their potential role in opening up new avenues of treatment…

Understanding the immunology of inflammatory bowel disease continues to underpin the vast majority of new therapies and identifies new targets.

Novel approaches, such as exploiting the antiinflammatory role of cannabinoid receptors, may also prove productive in the future.”

http://www.ncbi.nlm.nih.gov/pubmed/15930983

Cannabinoids for gastrointestinal diseases: potential therapeutic applications.

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“Delta(9)-Tetrahydrocannabinol (the active ingredient of marijuana), as well as endogenous and synthetic cannabinoids, exert many biological functions by activating two types of cannabinoid receptors, CB(1) and CB(2) receptors. CB(1) 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 (i.e., the endocannabinoids anandamide and 2-aracidonylglycerol) and mechanisms for endocannabinoid inactivation (i.e., 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 delta(9)-tetrahydrocannabinol are used as antiemetics.”

http://www.ncbi.nlm.nih.gov/pubmed/12517253

Endocannabinoids and the gastrointestinal tract.

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“In the past centuries, different preparations of marijuana have been used for the treatment of gastrointestinal (GI) disorders, such as GI pain, gastroenteritis and diarrhea.

 Delta9-tetrahydrocannabinol (THC; the active component of marijuana), as well as endogenous and synthetic cannabinoids, exert their biological functions on the gastrointestinal tract by activating two types of cannabinoid receptors, cannabinoid type 1 receptor (CB1 receptor) and cannabinoid type 2 receptor (CB2 receptor). While CB1 receptors are located in the enteric nervous system and in sensory terminals of vagal and spinal neurons and regulate neurotransmitter release, CB2 receptors are mostly distributed in the immune system, with a role presently still difficult to establish.

Under pathophysiological conditions, the endocannabinoid system conveys protection to the GI tract, eg from inflammation and abnormally high gastric and enteric secretion.

 For such protective activities, the endocannabinoid system may represent a new promising therapeutic target against different GI disorders, including frankly inflammatory bowel diseases (eg, Crohn’s disease), functional bowel diseases (eg, irritable bowel syndrome), and secretion- and motility-related disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/16751708