Blockade of cannabinoid 1 receptor improves glucose responsiveness in pancreatic beta cells.

Journal of Cellular and Molecular Medicine

“Cannabinoid 1 receptors (CB1Rs) are expressed in peripheral tissues, including islets of Langerhans, where their function(s) is under scrutiny. Using mouse β-cell lines, human islets and CB1R-null (CB1R-/- ) mice, we have now investigated the role of CB1Rs in modulating β-cell function and glucose responsiveness. Synthetic CB1R agonists diminished GLP-1-mediated cAMP accumulation and insulin secretion as well as glucose-stimulated insulin secretion in mouse β-cell lines and human islets. In addition, silencing CB1R in mouse β cells resulted in an increased expression of pro-insulin, glucokinase (GCK) and glucose transporter 2 (GLUT2), but this increase was lost in β cells lacking insulin receptor. Furthermore, CB1R-/- mice had increased pro-insulin, GCK and GLUT2 expression in β cells. Our results suggest that CB1R signalling in pancreatic islets may be harnessed to improve β-cell glucose responsiveness and preserve their function. Thus, our findings further support that blocking peripheral CB1Rs would be beneficial to β-cell function in type 2 diabetes.”

https://www.ncbi.nlm.nih.gov/pubmed/29431265

http://onlinelibrary.wiley.com/doi/10.1111/jcmm.13523/abstract

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Endocannabinoid system and cannabinoids in neurogenesis – new opportunities for neurological treatment? Reports from experimental studies.

“Neurogenesis is one of the most important phenomenona affecting human life. This process consists of proliferation, migration and differentiation of neuroblasts and synaptic integrations of newborn neurons.
Proliferation of new cells continues into old age, also in humans, although the most extensive process of cell formation occurs during the prenatal period. It is possible to distinguish two regions in the brain responsible for neurogenesis: the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ). Hippocampal neurogenesis is very sensitive to various physiological and pathological stimuli.
The functional integration of the newly-born dentate granule cells into hippocampal circuitry, and their ability to mediate long-term potentiation in DG, has led to the hypothesis that neurogenesis in the adult brain may play a key role in learning and memory function, as well as cognitive dysfunction in some diseases.
Brain disorders, such as neurodegenerative diseases or traumatic brain injuries, significantly affect migration, proliferation and differentiation of neural cells. In searching for the best neurological drugs protecting neuronal cells, stimulating neurogenesis, while also developing no side-effects, endocannabinoids proved to be a strong group of substances having many beneficial properties.
Therefore, the latest data is reviewed of the various experimental studies concerning the analysis of the most commonly studied cannabinoids and their impact on neurogenesis.”
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Analysis of cannabinoids in commercial hemp seed oil and decarboxylation kinetics studies of cannabidiolic acid (CBDA).

Journal of Pharmaceutical and Biomedical Analysis

“Hemp seed oil from Cannabis sativa L. is a very rich natural source of important nutrients, not only polyunsaturated fatty acids and proteins, but also terpenes and cannabinoids, which contribute to the overall beneficial effects of the oil.

Hence, it is important to have an analytical method for the determination of these components in commercial samples. At the same time, it is also important to assess the safety of the product in terms of amount of any psychoactive cannabinoid present therein.

This work presents the development and validation of a highly sensitive, selective and rapid HPLC-UV method for the qualitative and quantitative determination of the main cannabinoids, namely cannabidiolic acid (CBDA), tetrahydrocannabinolic acid (THCA), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN), cannabigerol (CBG) and cannabidivarin (CBDV), present in 13 commercial hemp seed oils.”

https://www.ncbi.nlm.nih.gov/pubmed/29182999

https://www.sciencedirect.com/science/article/pii/S0731708517322367?via%3Dihub

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Cannabidiol Limits T Cell–Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation

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“Cannabidiol (CBD) is a nonpsychoactive ingredient of marijuana (Cannabis sativa).

Collectively, our study demonstrates that CBD treatment markedly attenuates autoimmune myocarditis and improves myocardial dysfunction and heart failure primarily by its antiinflammatory and antifibrotic effects.

These results, coupled with the proven safety of CBD in human clinical trials and its current orphan drug approval by the FDA for different neurological disorders, suggest that it has tremendous therapeutic potential in the therapy of myocarditis with different etiologies and various autoimmune disorders. The latter is also supported by beneficial effects of CBD in preventing graft versus host disease after allogeneic hematopoietic cell transplantation in a recent phase II human study, as well as in mice with arthritis. Attenuation of the T cell–mediated injury by CBD also suggests that it may have therapeutic utility in management of organ transplantation/rejection.

In conclusion, CBD may represent a promising novel treatment for managing autoimmune myocarditis and possibly other autoimmune disorders and organ transplantation.”

https://www.ncbi.nlm.nih.gov/pubmed/26772776

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004721/

http://static.smallworldlabs.com/molmedcommunity/content/pdfstore/16_007_Lee.pdf

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Anti-Inflammatory Drugs and Herbs with Special Emphasis on Herbal Medicines for Countering Inflammatory Diseases and Disorders – A Review.

“Diseases with inflammatory etiopathology have increased in incidence in recent times. Drugs used for therapeutic management of such inflammatory diseases are relieving the ailment but at the same time also countering serious life-threatening consequences. Moreover, they are costly and rarely available at all places. In this context, research and development on medicinal herbs have opened a new era in the prophylactic and therapeutic management of inflammatory diseases.

OBJECTIVE:

To highlight the importance of anti-inflammatory medicine-synthetic drugs and natural herbs, their constituents, mechanism of action, benefits, side effects and future prospects. The overall aim is to provide better health services to patiens regardless of their background on equality basis.

RESULTS:

Anti-inflammatory herbs have proven beneficial by combating inflammatory responses that lead to severe abnormality in body systems. Inflammation though a protective response to infection or injury and may result in pathological outcome when aggravated or of severe degree thus needs an early intervention for proper resolution. Medicinal plants or their constituents are considered beneficial due to the properties i.e., satisfactory potency, ease of availability, cheapness, less or no side effects, safer and efficient as compared to the synthetic counterparts. These medicinal herbs contain phytoconstituents that can prevent undesirable inflammatory processes and also posses anti-inflammatory activity. Steroids, glycosides, phenolics, flavonoids, alkaloids, polysaccharides, terpenoids, cannabinoids, fatty acids are common phytoconstituents present in these plants. Different mechanisms have been explored for the anti-inflammatory action of these active ingredients. They may synergize the anti-inflammatory pathway enzymes, factors, proteins or interfere with these in the inflammatory pathway like lipooxygenases, cyclooxygenases, tumor necrosis factors, interleukins, prostaglandin, nitric oxide, mitogen-activated protein, nuclear factor, etc. Considering all the above-mentioned factors, further research from molecular to cellular level will enable a better understanding of the mechanisms. Common anti-inflammatory herbal plants are Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, Urtica dioica, Uncaria tomentosa, Vaccinium myrtillus, Olea europaea and much more. They are believed to be without side effects unlike the chemical counterparts or synthetic anti-inflammatory agents e.g. steroids, nonsteroid anti-inflammatory drugs, and immunosuppressant used for controlling and suppressing inflammatory crisis. A proper phytochemical, pharmacological and physiological evaluation will enable their safe and effective use in inflammatory conditions. Many of these anti-inflammatory drugs and herbal preparations have been patented with some under consideration.

CONCLUSION:

Natural herbs are safe, effective and better options as anti-inflammatory agents than synthetic ones. The phytoconstituents are as effective with the comparable mechanism of action as synthetic molecules. Future research should focus on molecular mechanisms of different beneficial applications of these herbal plants in various diseases. Recent patents on anti-inflammatory drugs and herbal plants have been covered which provide insight into the current status and future prospects in this field.”

https://www.ncbi.nlm.nih.gov/pubmed/29336271  http://www.eurekaselect.com/159064/article

“Cannabinoids as novel anti-inflammatory drugs”  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828614/

“Cannabinoids for the treatment of inflammation.” http://www.ncbi.nlm.nih.gov/pubmed/17520866

“Cannabis-based drugs have been shown to be effective in inflammatory diseases.” https://www.ncbi.nlm.nih.gov/pubmed/29110674

http://www.thctotalhealthcare.com/tag/anti-inflammatory/

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Betacaryophyllene – A phytocannabinoid as potential therapeutic modality for human sepsis?

Medical Hypotheses Home

“Sepsis is a clinical condition resulting from a dysregulated immune response to an infection that leads to organ dysfunction. Despite numerous efforts to optimize treatment, sepsis remains to be the main cause of death in most intensive care units.

The endogenous cannabinoid system (ECS) plays an important role in inflammation. Cannabinoid receptor 2 (CB2R) activation is immunosuppressive, which might be beneficial during the hyper-inflammatory phase of sepsis.

Beta-caryophyllene (BCP) is a non-psychoactive natural cannabinoid (phytocannabinoid) found in Cannabis sativa and in essential oils of spices and food plants, that acts as a selective agonist of CB2R.

We propose BCP administration as novel treatment to reduce hyper-inflammation in human sepsis.”

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Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco-2 cells.

 SAGE Journals

“Clostridium difficile toxin A is responsible for colonic damage observed in infected patients.

Drugs able to restore Clostridium difficile toxin A-induced toxicity have the potential to improve the recovery of infected patients. Cannabidiol is a non-psychotropic component of Cannabis sativa, which has been demonstrated to protect enterocytes against chemical and/or inflammatory damage and to restore intestinal mucosa integrity.

The purpose of this study was to evaluate (a) the anti-apoptotic effect and (b) the mechanisms by which cannabidiol protects mucosal integrity in Caco-2 cells exposed to Clostridium difficile toxin A.

RESULTS:

Clostridium difficile toxin A significantly decreased Caco-2 cells’ viability and reduced transepithelial electrical resistence values and RhoA guanosine triphosphate (GTP), bax, zonula occludens-1 and occludin protein expression, respectively. All these effects were significantly and concentration-dependently inhibited by cannabidiol, whose effects were completely abolished in the presence of the cannabinoid receptor type 1 (CB1) antagonist, AM251.

CONCLUSIONS:

Cannabidiol improved Clostridium difficile toxin A-induced damage in Caco-2 cells, by inhibiting the apoptotic process and restoring the intestinal barrier integrity, through the involvement of the CB1 receptor.”

https://www.ncbi.nlm.nih.gov/pubmed/29238589

“In the last decade, cannabinoids extracted from the marijuana plant (Cannabis sativa) and synthetic cannabinoids have shown numerous beneficial effects on gastrointestinal (GI) functions. Non-psychotropic phytocannabinoid cannabidiol (CBD) is one of the most interesting compounds, since it exerts a wide range of beneficial pharmacological actions on GI functions, ranging from antioxidant to antinflammatory activities. CBD has been shown to act as a non-competitive negative allosteric modulator of CB1 receptors. Notably, CBD is able to restore in vitro intestinal permeability increased by ethylenediaminetetraacetic acid (EDTA) or pro-inflammatory stimuli.

Clostridium difficile infection is the leading cause of hospital-acquired diarrhoea and pseudomembranous colitis. Clostridium difficile-Toxin A significantly affects enterocytes permeability leading to apoptosis and colonic mucosal damage.

In the present study, we showed that Cannabidiol, a non-psychotropic component of Cannabis sativa significantly inhibit the apoptosis rate in TcdA-exposed cells and restores barrier function by a significant RhoA GTP rescue.

We also provide evidence that the effects of Cannabidiol are mediated by CB-1 receptor.

Given the absence of any significant toxic effect in humans, cannabidiol may ideally represent an effective adjuvant treatment for Clostridium difficile-associated colitis.”   http://journals.sagepub.com/doi/10.1177/2050640617698622

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Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial

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“Research in both animals and humans indicates that cannabidiol (CBD) has antipsychotic properties.

The authors assessed the safety and effectiveness of CBD in patients with schizophrenia.

After 6 weeks of treatment, compared with the placebo group, the CBD group had lower levels of positive psychotic symptoms and were more likely to have been rated as improved and as not severely unwell by the treating clinician.

These findings suggest that CBD has beneficial effects in patients with schizophrenia. As CBD’s effects do not appear to depend on dopamine receptor antagonism, this agent may represent a new class of treatment for the disorder.”

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Analysis of cannabinoids in commercial hemp seed oil and decarboxylation kinetics studies of cannabidiolic acid (CBDA).

Journal of Pharmaceutical and Biomedical Analysis

“Hemp seed oil from Cannabis sativa L. is a very rich natural source of important nutrients, not only polyunsaturated fatty acids and proteins, but also terpenes and cannabinoids, which contribute to the overall beneficial effects of the oil.

Hence, it is important to have an analytical method for the determination of these components in commercial samples. At the same time, it is also important to assess the safety of the product in terms of amount of any psychoactive cannabinoid present therein.

This work presents the development and validation of a highly sensitive, selective and rapid HPLC-UV method for the qualitative and quantitative determination of the main cannabinoids, namely cannabidiolic acid (CBDA), tetrahydrocannabinolic acid (THCA), cannabidiol (CBD), tetrahydrocannabinol (THC), cannabinol (CBN), cannabigerol (CBG) and cannabidivarin (CBDV), present in 13 commercial hemp seed oils.

Moreover, since decomposition of cannabinoid acids generally occurs with light, air and heat, decarboxylation studies of the most abundant acid (CBDA) were carried out in both open and closed reactor and the kinetics parameters were evaluated at different temperatures in order to evaluate the stability of hemp seed oil in different storage conditions.”

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Anti-Inflammatory Activity in Colon Models Is Derived from Δ9-Tetrahydrocannabinolic Acid That Interacts with Additional Compounds in Cannabis Extracts.

“Inflammatory bowel diseases (IBDs) include Crohn’s disease, and ulcerative colitis. Cannabis sativa preparations have beneficial effects for IBD patients. However, C. sativa extracts contain hundreds of compounds. Although there is much knowledge of the activity of different cannabinoids and their receptor agonists or antagonists, the cytotoxic and anti-inflammatory activity of whole C. sativa extracts has never been characterized in detail with in vitro and ex vivo colon models.

Material and Methods: The anti-inflammatory activity of C. sativa extracts was studied on three lines of epithelial cells and on colon tissue. C. sativa flowers were extracted with ethanol, enzyme-linked immunosorbent assay was used to determine the level of interleukin-8 in colon cells and tissue biopsies, chemical analysis was performed using high-performance liquid chromatography, mass spectrometry and nuclear magnetic resonance and gene expression was determined by quantitative real-time PCR.

Results: The anti-inflammatory activity of Cannabis extracts derives from D9-tetrahydrocannabinolic acid (THCA) present in fraction 7 (F7) of the extract. However, all fractions of C. sativa at a certain combination of concentrations have a significant increased cytotoxic activity. GPR55 receptor antagonist significantly reduces the anti-inflammatory activity of F7, whereas cannabinoid type 2 receptor antagonist significantly increases HCT116 cell proliferation. Also, cannabidiol (CBD) shows dose dependent cytotoxic activity, whereas anti-inflammatory activity was found only for the low concentration of CBD, and in a bell-shaped rather than dose-dependent manner. Activity of the extract and active fraction was verified on colon tissues taken from IBD patients, and was shown to suppress cyclooxygenase-2 (COX2) and metalloproteinase-9 (MMP9) gene expression in both cell culture and colon tissue.

Conclusions: It is suggested that the anti-inflammatory activity of Cannabis extracts on colon epithelial cells derives from a fraction of the extract that contains THCA, and is mediated, at least partially, via GPR55 receptor. The cytotoxic activity of the C. sativa extract was increased by combining all fractions at a certain combination of concentrations and was partially affected by CB2 receptor antagonist that increased cell proliferation. It is suggested that in a nonpsychoactive treatment for IBD, THCA should be used rather than CBD.”

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