Pharmacological blockade of 2-AG degradation ameliorates clinical, neuroinflammatory and synaptic alterations in experimental autoimmune encephalomyelitis

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The endocannabinoid system (ECS) is critically involved in the pathophysiology of Multiple Sclerosis (MS), a neuroinflammatory and neurodegenerative disease of the central nervous system (CNS). Over the past decade, the neuroprotective and anti-inflammatory effects of the ECS have been studied, and inhibiting the degradation of the endocannabinoid 2-arachydonoylglycerol (2-AG) is emerging as a promising strategy to counteract brain damage in MS. In this study, a systemic and preventive in vivo treatment with MAGLi 432, the reversible inhibitor of monoacylglycerol lipase (MAGLi), was performed in experimental autoimmune encephalomyelitis (EAE) mice. Clinical, biochemical, electrophysiological and immunofluorescence analyses were carried out to evaluate the impact of the drug on motor disability, neuroinflammation and synaptic damage. MAGLi 432 induced a less severe EAE disease, accompanied by an increase of 2-AG and a reduction of acid arachidonic (AA) and prostaglandins (PGs) brain levels.

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Mutual Links between the Endocannabinoidome and the Gut Microbiome, with Special Reference to Companion Animals: A Nutritional Viewpoint

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Dysbiosis, which is an imbalance of gut microbial composition and function, can be caused by several external as well as internal factors, contributing to the onset of human and animal disorders, not limited to the gastrointestinal tract. Accordingly, the mechanisms leading to disease development involve a crucial interaction between the gut microbiota, their metabolic products, and the host. The expanded endocannabinoid system, also known as the “endocannabinoidome”, includes endocannabinoids (e.g., anandamide) and endocannabinoid-like mediators (e.g., palmitoylethanolamide), their receptors and metabolic enzymes. Dysregulation of this newly recognized endogenous system is also involved in several diseases. It is becoming increasingly apparent that a link between the endocannabinoidome and the gut microbiome exists. Here, we review some of the latest discoveries related to the functional link between these two complex systems and the disorders emerging from the malfunctioning of such a mutual interaction: for example, idiopathic inflammation, chronic enteropathies, metabolic disease and certain neuroinflammatory disorders. It is expected that in the near future new nutritional tools will emerge based on the expanding knowledge in this cutting-edge field.

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Analysis of Anti-Cancer and Anti-Inflammatory Properties of 25 High-THC Cannabis Extracts

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Cannabis sativa is one of the oldest cultivated plants. Many of the medicinal properties of cannabis are known, although very few cannabis-based formulations became prescribed drugs. Previous research demonstrated that cannabis varieties are very different in their medicinal properties, likely due to the entourage effect—the synergistic or antagonistic effect of various cannabinoids and terpenes. In this work, we analyzed 25 cannabis extracts containing high levels of delta-9- tetrahydrocannabinol (THC). We used HCC1806 squamous cell carcinoma and demonstrated various degrees of efficiency of the tested extracts, from 66% to 92% of growth inhibition of cancer cells. Inflammation was tested by induction of inflammation with TNF-α/IFN-γ in WI38 human lung fibroblasts.

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The non-euphoric phytocannabinoid cannabidivarin counteracts intestinal inflammation in mice and cytokine expression in biopsies from UC pediatric patients

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Patients with ulcerative colitis (UC) using marijuana have been reported to experience symptomatic benefit. Cannabidivarin (CBDV) is a safe non-psychoactive phytocannabinoid able to activate and desensitize TRPA1, a member of the TRP channels superfamily, which plays a pivotal role in intestinal inflammation. Here, we have investigated the potential intestinal anti-inflammatory effect of CBDV in mice and in biopsies from pediatric patients with active UC

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Differential Effects of D9 Tetrahydrocannabinol (THC)- and Cannabidiol (CBD)-Based Cannabinoid Treatments on Macrophage Immune Function In Vitro and on Gastrointestinal Inflammation in a Murine Model

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Authors Zhanna Yekhtin, Iman Khuja, David Meiri, Reuven Or, Osnat Almogi-Hazan Published 26 July 2022 DOI: 10.3390/biomedicines10081793 Citations MDPI and ACS Style Yekhtin, Z.; Khuja, I.; Meiri, D.; Or, R.;…

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Therapeutic Applications of Terpenes on Inflammatory Diseases

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In this context, terpenes are a highly diverse family of natural products which are synthesized by plants. This family have approximately 55,000 members with different chemical structures, presenting potential practical applications (Prakash, 2017; Serrano Vega et al., 2018). For this reason, it has been reported that terpenoids could ameliorate various symptoms caused by inflammation, inhibiting various steps of inflammatory processes. However, due to their low solubility and high instability, some alternatives, such as nanotechnology, have been explored.

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Daily Cannabis Use is Associated With Lower CNS Inflammation in People With HIV

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Recent cannabis exposure has been associated with lower rates of neurocognitive impairment in people with HIV (PWH). Cannabis’s anti-inflammatory properties may underlie this relationship by reducing chronic neuroinflammation in PWH. This study examined relations between cannabis use and inflammatory biomarkers in cerebrospinal fluid (CSF) and plasma, and cognitive correlates of these biomarkers within a community-based sample of PWH.

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CBD Promotes Oral Ulcer Healing via Inhibiting CMPK2-Mediated Inflammasome

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Oral ulcer is a common oral inflammatory lesion accompanied by severe pain but with few effective treatments. Cannabidiol (CBD) is recently emerging for its therapeutic potential in a range of diseases, including inflammatory conditions and cancers. Here we show that CBD oral spray on acid- or trauma-induced oral ulcers on mice tongue inhibits inflammation, relieves pain, and accelerates lesion closure

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Activation of Cannabinoid Receptor 2 Prevents Colitis-Associated Colon Cancer through Myeloid Cell De-activation Upstream of IL-22 Production

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Authors: William Becker, Haider Rasheed Alrafa,Kiesha Wilson, Kathryn Miranda, Courtney Culpepper, Ioulia Chatzistamou, Guoshuai Cai, Mitzi Nagarkatti, Prakash S. Nagarkatti Published in Iscience August 2020 Abstract Summary Intestinal disequilibrium leads…

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A molecular basis for the anti-inflammatory and anti-fibrosis properties of cannabidiol

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Authors: Falone Sunda, Afolake Arowolo Published in The FASEB Journal April 2020 Abstract Cannabidiol (CBD) is considered a non-psychoactive, antioxidant, and anti-inflammatory compound derived from the Cannabis sativa plant. There…

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A molecular basis for the anti‐inflammatory and anti‐fibrosis properties of cannabidiol

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Authors: Falone Sunda, Afolake Arowolo Published in The FASEB Journal September 2020 Abstract Cannabidiol (CBD) is considered a non‐psychoactive, antioxidant, and anti‐inflammatory compound derived from the Cannabis sativa plant. There…

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Use of cannabinoids in cancer patients: A Society of Gynecologic Oncology (SGO) clinical practice statement.

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Authors: B. Whitcomb, C. Lutman, M. Pearl, E. Medlin, E. Prendergast, K. Robison, W. Burke
Gynecologic Oncology, 10 January 2020
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Tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN) affect the human endocannabinoid system. Cannabinoids reduce chemotherapy induced nausea or vomiting (CINV) and neuropathic pain. Each state has its own regulations for medical and recreational cannabis use. Ef…

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