“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]]>
Category Archives: Inflammatory Bowel Disease
Manipulation of the Endocannabinoid System in Colitis: A Comprehensive Review.
“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 “Plant cannabinoids THC and CBD proved beneficial in DNBS-induced colitis in a bell-shaped dose-related response, but more importantly, the effects of the phytocannabinoids were additive, as CBD increased an ineffective THC dose to the level of an effective one.” https://academic.oup.com/ibdjournal/article/23/2/192/4347176The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease
“In ancient medicine, extracts of the marijuana plant Cannabis sativa were used against diseases of the gastrointestinal (GI) tract. Today, our knowledge of the ingredients of the Cannabis plant has remarkably advanced enabling us to use a variety of herbal and synthetic cannabinoid (CB) compounds to study the endocannabinoid system (ECS), a physiologic entity that controls tissue homeostasis with the help of endogenously produced CBs and their receptors. After many anecdotal reports suggested beneficial effects of Cannabis in GI disorders, it was not surprising to discover that the GI tract accommodates and expresses all the components of the ECS. The following review summarizes important and recent findings on the role of CB receptors and their ligands in the GI tract with emphasis on GI disorders, such as irritable bowel syndrome, inflammatory bowel disease, and colon cancer.” https://www.ncbi.nlm.nih.gov/pubmed/27561826]]>
Therapeutic Use of Cannabis in Inflammatory Bowel Disease.
“The marijuana plant Cannabis sativa and its derivatives, cannabinoids, have grown increasingly popular as a potential therapy for inflammatory bowel disease (IBD). Studies have shown that modulation of the endocannabinoid system, which regulates various functions in the body and has been shown to play a key role in the pathogenesis of IBD, has a therapeutic effect in mouse colitis. The plant Cannabis sativa has been used in medicinal practice for thousands of years. Anecdotal reports have suggested a therapeutic role for cannabis in the treatment of IBD for hundreds of years. A case report from 1990 describes patients with IBD maintaining remission of disease via cannabis use. Cannabinoids appear to have a clear role in gut pathology and offer a potential target for drug intervention in the treatment of IBD. Cannabis seems to be of symptomatic benefit to patients often refractory to conventional medicines.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5193087/]]>
Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells.
“Human Gingival Mesenchymal Stem Cells (hGMSCs) are multipotential cells that can expand and differentiate in culture under specific and standardized conditions.
In the present study, we have investigated whether in vitro pre-treatment of hGMSCs with Cannabidiol(CBD) can influence their expression profile, improving the therapeutic potential of this cell culture.
In conclusion, the present study will provide a new simple and reproducible method for preconditioning hGMSCs with CBD, before transplantation, as an interesting strategy for improving the hGMSCs molecular phenotype, reducing the risk of immune or inflammatory reactions in the host, and in parallel, for increasing their survival and thus, their long-term therapeutic efficacy.”
Anti-inflammatory effect of cannabinoid agonist WIN55, 212 on mouse experimental colitis is related to inhibition of p38MAPK.
“To investigate the anti-inflammatory effect and the possible mechanisms of an agonist of cannabinoid (CB) receptors, WIN55-212-2 (WIN55), in mice with experimental colitis, so as to supply experimental evidence for its clinical use in future.
These results confirmed the anti-inflammatory effect and protective role of WIN55 on the mice with experimental colitis, and revealed that this agent exercises its action at least partially by inhibiting p38MAPK.
Furthermore, the results showed that SB203580, affected the expression of CB1 and CB2 receptors in the mouse colon, suggesting a close linkage and cross-talk between the p38MAPK signaling pathway and the endogenous CB system.”
Cannabinoid Receptor 2 Functional Variant Contributes to the Risk for Pediatric Inflammatory Bowel Disease.
“We conducted a case-control association analysis to establish the role of a common CB2 functional variant, Q63R, in the susceptibility to inflammatory bowel disease (IBD).
Endocannabinoids may limit intestinal inflammation through cannabinoid receptor 1 and/or 2 (CB1, CB2).
The CB2-Q63R variant contributes to the risk for pediatric IBD, in particular CD. The R63 variant is associated with a more severe phenotype in both UC and CD.
Taken together, our data point toward the involvement of the CB2 receptor in the pathogenesis and clinical features of pediatric IBD.”
Medical Cannabis – another piece in the mosaic of autoimmunity?
“Legalization of cannabis’ medicinal use is rapidly increasing worldwide, raising the need to evaluate medical implications of cannabis. Currently evidence supports cannabis and its active ingredients as an immune-modulating agents, affecting T-cells, B-cells, Monocytes and Microglia-cells, causing an overall reduction in pro-inflammatory cytokine expression and an increase in anti-inflammatory cytokines. Due to the supporting evidence of cannabinoids as an immune-modulating agent, research focusing on cannabinoids and autoimmunity has emerged. Several clinical trials in multiple sclerosis, inflammatory bowel disease and fibromyalgia suggest cannabis’ effectiveness as an immune-modulator. However, contradicting results and lack of large scale clinical trials obscure these results. Though lacking clinical research, in-vitro and in-vivo experiments in rheumatoid arthritis, diabetes type 1 and systemic sclerosis, demonstrate a correlation between disease activity and cannabinoids.”
Prevalence and Patterns of Marijuana Use in Young Adults with Inflammatory Bowel Disease.
“Recent studies in adults report symptom relief with marijuana use in patients with inflammatory bowel disease (IBD).
We assessed the prevalence, pattern, effects and adverse effects of marijuana use in young adults with IBD.
We conducted a prospective questionnaire survey study at a pediatric IBD clinic. All patients (18 to 21 years of age) answered anonymous questionnaires about demographics, IBD, medications and marijuana use.
Overall, 98% of patients supported legalization of marijuana and 85% were interested in using medical marijuana if it became legally available.
We found a high rate of marijuana use in our cohort of young adults with IBD. Majority of users report symptom improvement but do not inform physicians. Future well controlled studies are necessary to assess role of marijuana in IBD therapy.”
Cannabinoids, inflammation, and fibrosis.
“Cannabinoids apparently act on inflammation through mechanisms different from those of agents such as nonsteroidal anti-inflammatory drugs (NSAIDs).
As a class, the cannabinoids are generally free from the adverse effects associated with NSAIDs. Their clinical development thus provides a new approach to treatment of diseases characterized by acute and chronic inflammation and fibrosis.
A concise survey of the anti-inflammatory actions of the phytocannabinoids Δ9-tetrahydrocannabinol (THC), cannabidiol, cannabichromene, and cannabinol is presented.
The endogenous cannabinoids, including the closely related lipoamino acids, are then discussed.
The review concludes with a presentation of a possible mechanism for the anti-inflammatory and antifibrotic actions of these substances.
Thus, several cannabinoids may be considered candidates for development as anti-inflammatory and antifibrotic agents.
Of special interest is their possible use for treatment of chronic inflammation, a major unmet medical need.”