Cannabis for Ulcerative Colitis and Crohn’s Disease treatment

“Chemicals found in cannabis could prove an effective treatment for the inflammatory bowel diseases Ulcerative Colitis and Crohn’s Disease, say scientists.

Laboratory tests have shown that two compounds found in the cannabis plant – the cannabinoids THC and cannabidiol – interact with the body’s system that controls gut function.

Crohn’s Disease and Ulcerative Colitis, which affect about one in every 250 people in Northern Europe, are caused by both genetic and environmental factors. The researchers believe that a genetic susceptibility coupled with other triggers, such as diet, stress or bacterial imbalance, leads to a defective immune response.

Dr Karen Wright, Peel Trust Lecturer in Biomedicine at Lancaster University, will be presenting her soon-to-be published work at The British Pharmacological Society’s Winter Meeting in London today (Thursday).

She said: “The lining of the intestines provides a barrier against the contents of the gut but in people with Crohn’s Disease this barrier leaks and bacteria can escape into the intestinal tissue leading to an inappropriate immune response.

“If we could find a way to restore barrier integrity in patients we may be able to curb the inflammatory immune response that causes these chronic conditions.”

Dr Wright, working with colleagues at the School of Graduate Entry Medicine and Health in Derby, has shown that cells that react to cannabinoid compounds play an important role in normal gut function as well as the immune system’s inflammatory response.

“The body produces its own cannabinoid molecules, called endocannabinoids, which we have shown increase the permeability of the epithelium during inflammation, implying that overproduction may be detrimental,” said Dr Wright.

“However, we were able to reverse this process using plant-derived cannabinoids, which appeared to allow the epithelial cells to form tighter bonds with each other and restore the membrane barrier.”

The research was carried out using cell cultures in a dish but, interestingly, when the team attempted to mimic the conditions of the gut by reducing the amount of oxygen in the cells’ environment, much lower concentrations of cannabinoid were needed to produce the same effect.

Dr Wright added: “What is also encouraging is that while THC has psychoactive properties and is responsible for the ‘high’ people experience when using cannabis, cannabidiol, which has also proved effective in restoring membrane integrity, does not possess such properties.”

The British Pharmacological Society (BPS) – the primary UK learned society concerned with research into drugs and the way they work – is hosting its annual Winter Meeting in London, attracting experts from across the world.

The three-day conference, running from 15 to 17 December 2009, will hear presentations on the latest pharmacological developments to tackle a range of conditions and diseases.”

http://www.news-medical.net/news/20091217/Cannabis-for-Ulcerative-Colitis-and-Crohns-Disease-treatment.aspx

Cannabis Induces a Clinical Response in Patients with Crohn’s Disease: a Prospective Placebo-Controlled Study.

“The marijuana plant Cannabis sativa has been reported to produce beneficial effects for patients with inflammatory bowel diseases, but these have not been investigated in controlled trials. We performed a prospective trial to determine whether cannabis can induce remission in patients with Crohn’s disease…

Complete remission was achieved by 5/11 subjects in the cannabis group (45%)… Three patients in the cannabis group were weaned from steroid dependency. Subjects receiving cannabis reported improved appetite and sleep, with no significant side effects.

CONCLUSION:

Although the primary endpoint of the study (induction of remission) was not achieved, a short course (8 week) of THC-rich cannabis produced significant clinical, steroid-free benefits to 11 patients with active CD, compared to placebo, without side effects.

Further studies, with larger patient groups and a non-smoking mode of intake, are warranted. ClinicalTrials.gov NCT01040910.”

http://www.ncbi.nlm.nih.gov/pubmed/23648372

Treatment of Crohn’s Disease with Cannabis: An Observational Study

“The marijuana plant cannabis is known to have therapeutic effects, including improvement of inflammatory processes. However, no report of patients using cannabis for Crohn’s disease (CD) was ever published.

OBJECTIVES:

To describe the effects of cannabis use in patients suffering from CD.

RESULTS:

Of the 30 patients 21 improved significantly after treatment with cannabis… The need for other medication was significantly reduced. Fifteen of the patients had 19 surgeries during an average period of 9 years before cannabis use, but only 2 required surgery during an average period of 3 years of cannabis use.

CONCLUSIONS:

This is the first report of cannabis use in Crohn’s disease in humans. The results indicate that cannabis may have a positive effect on disease activity, as reflected by reduction in disease activity index and in the need for other drugs and surgery. Prospective placebo-controlled studies are warranted to fully evaluate the efficacy and side effects of cannabis in CD.”

Full Text: http://www.ima.org.il/IMAJ/ViewArticle.aspx?year=2011&month=08&page=455

Cannabis use amongst patients with inflammatory bowel disease.

“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

Beta-caryophyllene is a dietary cannabinoid

“The psychoactive cannabinoids from Cannabis sativa L. and the arachidonic acid-derived endocannabinoids are nonselective natural ligands for cannabinoid receptor type 1 (CB(1)) and CB(2) receptors. Although the CB(1) receptor is responsible for the psychomodulatory effects, activation of the CB(2) receptor is a potential therapeutic strategy for the treatment of inflammation, pain, atherosclerosis, and osteoporosis.

 Here, we report that the widespread plant volatile (E)-beta-caryophyllene [(E)-BCP] selectively binds to the CB(2) receptor and that it is a functional CB(2) agonist.

 Intriguingly, (E)-BCP is a common constituent of the essential oils of numerous spice and food plants and a major component in Cannabis.

 …this natural product exerts cannabimimetic effects in vivo. These results identify (E)-BCP as a functional nonpsychoactive CB(2) receptor ligand in foodstuff and as a macrocyclic antiinflammatory cannabinoid in Cannabis…

 Because (E)-BCP is a major constituent in Cannabis essential oil and shows significant cannabimimetic effects, it may also contribute to the overall effect of Cannabis preparations…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2449371/

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

“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.

“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

“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.

“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.

“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