Potential of plant-sourced phenols for inflammatory bowel disease.

“Inflammatory bowel disease (IBD) is an uncontrolled chronic inflammatory intestinal disorder, which requires medications for long-term therapy. Facing the challenges of severe side effects and drug resistance of conventional medications, to develop the strategies meet the stringent safety and effectiveness in the long-term treatment are urgent in the clinics.

In this regard, a growing body of evidence confirms plant-sourced phenols, such as flavonoids, catechins, stilbenes, coumarins, quinones, lignans, phenylethanoids, cannabinoid phenols, tannins, phenolic acids and hydroxyphenols, exert potent protective benefits with fewer undesirable effects in conditions of acute or chronic intestinal inflammation through improvement of colonic oxidative and pro-inflammatory status, preservation of the epithelial barrier function and modulation of gut microbiota.

In this review, the great potential of plant-sourced phenols and their action mechanisms for the treatment or prevention of IBD in recent research are summarized, which may help the further development of new preventive/adjuvant regimens for IBD.”

https://www.ncbi.nlm.nih.gov/pubmed/28990509

http://www.eurekaselect.com/156267/article

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Endocannabinoid-related compounds in gastrointestinal diseases.

Journal of Cellular and Molecular Medicine

“The endocannabinoid system (ECS) is an endogenous signalling pathway involved in the control of several gastrointestinal (GI) functions at both peripheral and central levels. In recent years, it has become apparent that the ECS is pivotal in the regulation of GI motility, secretion and sensitivity, but endocannabinoids (ECs) are also involved in the regulation of intestinal inflammation and mucosal barrier permeability, suggesting their role in the pathophysiology of both functional and organic GI disorders. Genetic studies in patients with irritable bowel syndrome (IBS) or inflammatory bowel disease have indeed shown significant associations with polymorphisms or mutation in genes encoding for cannabinoid receptor or enzyme responsible for their catabolism, respectively. Furthermore, ongoing clinical trials are testing EC agonists/antagonists in the achievement of symptomatic relief from a number of GI symptoms. Despite this evidence, there is a lack of supportive RCTs and relevant data in human beings, and hence, the possible therapeutic application of these compounds is raising ethical, political and economic concerns. More recently, the identification of several EC-like compounds able to modulate ECS function without the typical central side effects of cannabino-mimetics has paved the way for emerging peripherally acting drugs. This review summarizes the possible mechanisms linking the ECS to GI disorders and describes the most recent advances in the manipulation of the ECS in the treatment of GI diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/28990365

http://onlinelibrary.wiley.com/doi/10.1111/jcmm.13359/abstract

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Cannabinoid Receptor-2 Ameliorates Inflammation in Murine Model of Crohn’s Disease.

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“Cannabinoid receptor stimulation may have positive symptomatic effects on inflammatory bowel disease [IBD] patients through analgesic and anti-inflammatory effects.

The cannabinoid 2 receptor [CB2R] is expressed primarily on immune cells, including CD4+ T cells, and is induced by active inflammation in both humans and mice. We therefore investigated the effect of targeting CB2R in a preclinical IBD model.

 In summary, the endocannabinoid system is induced in murine ileitis but is downregulated in chronic murine and human intestinal inflammation, and CB2R activation attenuates murine ileitis, establishing an anti-inflammatory role of the endocannabinoid system.”

https://www.ncbi.nlm.nih.gov/pubmed/28981653

https://academic.oup.com/ecco-jcc/article-abstract/doi/10.1093/ecco-jcc/jjx096/3977952/Cannabinoid-Receptor-2-Ameliorates-Inflammation-in?redirectedFrom=fulltext

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Cannabidiol and Palmitoylethanolamide are anti-inflammatory in the acutely inflamed human colon.

Clinical Science “We sought to quantify the anti-inflammatory effects of two cannabinoid drugs: cannabidiol (CBD) and palmitoylethanolamide (PEA), in cultured cell lines and compared this effect with experimentally inflamed explant human colonic tissue.  These effects were explored in acutely and chronically inflamed colon, using inflammatory bowel disease and appendicitis explants.

Results:   IFNγ and TNFα treatment increased phosphoprotein and cytokine levels in Caco-2 cultures and colonic explants.  Phosphoprotein levels were significantly reduced by PEA or CBD in Caco-2 cultures and colonic explants.  CBD and PEA prevented increases in cytokine production in explant colon, but not in Caco-2 cells. CBD effects were blocked by the CB2antagonist AM630 and TRPV1 antagonist SB366791.  PEA effects were blocked by the PPARα antagonist GW6471.  PEA and CBD were anti-inflammatory in IBD and appendicitis explants.

Conclusion: PEA and CBD are anti-inflammatory in the human colon.  This effect is not seen in cultured epithelial cells. Appropriately sized clinical trials should assess their efficacy.”

https://www.ncbi.nlm.nih.gov/pubmed/28954820

http://www.clinsci.org/content/early/2017/09/26/CS20171288

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Cannabis in Inflammatory Bowel Diseases: from Anecdotal Use to Medicalization?

“Inflammatory bowel diseases (IBD) are disorders of chronic intestinal inflammation of unknown etiology. The basic pathophysiological process is that of immune mediated inflammation affecting the intestinal tract. This process is dependent on and governed by both genetic and environmental factors. There are two distinct forms of IBD – ulcerative colitis and Crohn’s disease.

There is no curative medical treatment. Furthermore, over 30% of patients, and over 70% with Crohn’s disease, will need surgical intervention for their disease. Thus, it comes as no surprise that many patients will turn to complementary or alternative medicine at some stage of their disease. Recent information reveals that between 16% and 50% of patients admit to having tried marijuana for their symptoms.

There is a long list of gastrointestinal symptoms that have been reported to be relieved by cannabis. These include anorexia, nausea, abdominal pain, diarrhea, gastroparesis – all of which can be part of IBD. These effects are related to the fact that the gastrointestinal tract is rich in cannabinoid (CB) receptors and their endogenous ligands, comprising together the endocannabinoid system (ECS).

In conclusion, use of cannabis is common in IBD, and it seems to be mostly safe. Accumulating preliminary data from human studies support a beneficial role of cannabinoids in IBD.”

https://www.ima.org.il/FilesUpload/IMAJ/0/228/114217.pdf

https://www.ima.org.il/imaj/ViewArticle.aspx?aId=4045

https://www.ncbi.nlm.nih.gov/pubmed/28457058

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Low-Dose Cannabidiol Is Safe but Not Effective in the Treatment for Crohn’s Disease, a Randomized Controlled Trial.

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“Cannabidiol (CBD) is an anti-inflammatory cannabinoid shown to be beneficial in a mouse model of IBD. Lacking any central effect, cannabidiol is an attractive option for treating inflammatory diseases. In this study of moderately active Crohn’s disease, CBD was safe but had no beneficial effects. This could be due to lack of effect of CBD on Crohn’s disease, but could also be due to the small dose of CBD, the small number of patients in the study, or the lack of the necessary synergism with other cannabinoids.”  https://www.ncbi.nlm.nih.gov/pubmed/28349233

“Cannabis induces a clinical response in patients with Crohn’s disease: a prospective placebo-controlled study. We performed a prospective trial to determine whether cannabis can induce remission in patients with Crohn’s disease. Complete remission was achieved by 5 of 11 subjects in the cannabis group and 1 of 10 in the placebo group. A short course (8 weeks) of THC-rich cannabis produced significant clinical, steroid-free benefits to 10 of 11 patients with active Crohn’s disease, compared with placebo, without side effects.”  https://www.ncbi.nlm.nih.gov/pubmed/23648372

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Cannabinoids for treating inflammatory bowel diseases: where are we and where do we go?

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“Fifty years after the discovery of Δ9-tetrahydrocannabinol (THC) as the psychoactive component of Cannabis, we are assessing the possibility of translating this herb into clinical treatment of inflammatory bowel diseases (IBDs).

Here, a discussion on the problems associated with a potential treatment is given.

From first surveys and small clinical studies in patients with IBD we have learned that Cannabis is frequently used to alleviate diarrhea, abdominal pain, and loss of appetite.

Single ingredients from Cannabis, such as THC and cannabidiol, commonly described as cannabinoids, are responsible for these effects. Synthetic cannabinoid receptor agonists are also termed cannabinoids, some of which, like dronabinol and nabilone, are already available with a narcotic prescription.

Recent data on the effects of Cannabis/cannabinoids in experimental models of IBD and in clinical trials with IBD patients have been reviewed using a PubMed database search. A short background on the endocannabinoid system is also provided.

Expert commentary: Cannabinoids could be helpful for certain symptoms of IBD, but there is still a lack of clinical studies to prove efficacy, tolerability and safety of cannabinoid-based medication for IBD patients, leaving medical professionals without evidence and guidelines.”

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Cannabinoids as gastrointestinal anti-inflammatory drugs.

Related image

“In this mini-review, we focus on the potential of the endocannabinoid system as a target for novel therapies to treat gastrointestinal (GI) inflammation. We discuss the organization of the endocannabinoid signaling and present possible pharmacological sites in the endocannabinoid system. We also refer to recent clinical findings in the field. Finally, we point at the potential use of cannabinoids at low, non-psychoactive doses to counteract non-inflammatory pathological events in the GI tract, like chemotherapy-induced diarrhea, as evidenced by Abalo et al. in the rat model.”

https://www.ncbi.nlm.nih.gov/pubmed/28239924

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Gut-brain axis: Role of lipids in the regulation of inflammation, pain and CNS diseases.

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“The human gut is a composite anaerobic environment with a large, diverse and dynamic enteric microbiota, represented by more than 100 trillion microorganisms, including at least 1000 distinct species. The discovery that a different microbial composition can influence behavior and cognition, and in turn the nervous system can indirectly influence enteric microbiota composition, has significantly contributed to establish the well-accepted concept of gut-brain axis.

This hypothesis is supported by several evidence showing mutual mechanisms, which involve the vague nerve, the immune system, the hypothalamic-pituitary-adrenal (HPA) axis modulation and the bacteria-derived metabolites. Many studies have focused on delineating a role for this axis in health and disease, ranging from stress-related disorders such as depression, anxiety and irritable bowel syndrome (IBS) to neurodevelopmental disorders, such as autism, and to neurodegenerative diseases, such as Parkinson Disease, Alzheimer Disease etc.

Based on this background, and considering the relevance of alteration of the symbiotic state between host and microbiota, this review focuses on the role and the involvement of bioactive lipids, such as the N-acylethanolamine (NAE) family whose main members are N-arachidonoylethanolamine (AEA), palmitoylethanolamide (PEA) and oleoilethanolamide (OEA), and short chain fatty acids (SCFAs), such as butyrate, belonging to a large group of bioactive lipids able to modulate peripheral and central pathologic processes.

It is well established their effective role in inflammation, acute and chronic pain, obesity and central nervous system diseases. It has been shown a possible correlation between these lipids and gut microbiota through different mechanisms.

Indeed, systemic administration of specific bacteria can reduce abdominal pain through the involvement of cannabinoid receptor 1 in rat; on the other hand, PEA reduces inflammation markers in a murine model of inflammatory bowel disease (IBD), and butyrate, producted by gut microbiota, is effective in reducing inflammation and pain in irritable bowel syndrome and IBD animal models.

In this review, we underline the relationship among inflammation, pain, microbiota and the different lipids, focusing on a possible involvement of NAEs and SCFAs in the gut-brain axis and their role in central nervous system diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/28215162

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Manipulation of the Endocannabinoid System in Colitis: A Comprehensive Review.

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“Inflammatory bowel disease (IBD) is a lifelong disease of the gastrointestinal tract whose annual incidence and prevalence is on the rise. Current immunosuppressive therapies available for treatment of IBD offer limited benefits and lose effectiveness, exposing a significant need for the development of novel therapies. In the clinical setting, cannabis has been shown to provide patients with IBD symptomatic relief, although the underlying mechanisms of their anti-inflammatory effects remain unclear.

RESULTS:

Cannabinoid receptors 1 and 2, endogenous cannabinoids, and atypical cannabinoids are upregulated in inflammation, and their presence and stimulation attenuate murine colitis, whereas cannabinoid receptor antagonism and cannabinoid receptor deficient models reverse these anti-inflammatory effects. In addition, inhibition of endocannabinoid degradation through monoacylglycerol lipase and fatty acid amide hydrolase blockade can also attenuate colitis development, and is closely linked to cannabinoid receptor expression.

CONCLUSIONS:

Although manipulation of the endocannabinoid system in murine colitis has proven to be largely beneficial in attenuating inflammation, there is a paucity of human study data. Further research is essential to clearly elucidate the specific mechanisms driving this anti-inflammatory effect for the development of therapeutics to target inflammatory disease such as IBD.”

https://www.ncbi.nlm.nih.gov/pubmed/28079617

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