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Combination of Cannabinoids, Δ9- Tetrahydrocannabinol and Cannabidiol, Ameliorates Experimental Multiple Sclerosis by Suppressing Neuroinflammation Through Regulation of miRNA-Mediated Signaling Pathways

Multiple sclerosis (MS) is a chronic and disabling disorder of the central nervous system (CNS) characterized by neuroinflammation leading to demyelination. Recently a combination of Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) extracted from Cannabis has been approved in many parts of the world to treat MS-related spasticity. THC+CBD combination was also shown to suppresses neuroinflammation, although the mechanisms remain to be further elucidated. In the current study, we demonstrate…

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Multiple sclerosis (MS) is a chronic and disabling disorder of the central nervous system (CNS) characterized by neuroinflammation leading to demyelination. Recently a combination of Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) extracted from Cannabis has been approved in many parts of the world to treat MS-related spasticity. THC+CBD combination was also shown to suppresses neuroinflammation, although the mechanisms remain to be further elucidated. In the current study, we demonstrate that THC+CBD combination therapy (10 mg/kg each) but not THC or CBD alone, attenuates murine experimental autoimmune encephalomyelitis (EAE) by reducing neuroinflammation and suppression of Th17 and Th1 cells. These effects were mediated through CB1 and CB2 receptors inasmuch as, THC+CBD failed to ameliorate EAE in mice deficient in CB1 and CB2. THC+CBD treatment also caused a decrease in the levels of brain infiltrating CD4+ T cells and pro-inflammatory molecules (IL-17, INF-γ, TNF-α, IL-1β, IL-6, and TBX21), while increasing anti-inflammatory phenotype such as FoxP3, STAT5b, IL-4, IL-10, and TGF-β. Also, the brain-derived cells showed increased apoptosis along with decreased percentage in G0/G1 phase with increased percentage in G2/M phase of cell cycle. miRNA microarray analysis of brain-derived CD4+ T cells revealed that THC+CBD treatment significantly down-regulated miR-21a-5p, miR-31-5p, miR-122-5p, miR-146a-5p, miR-150-5p, miR-155-5p, and miR-27b-5p while upregulating miR-706-5p and miR-7116. Pathway analysis showed that majority of the down-regulated miRs targeted molecules involved in cycle arrest and apoptosis such as CDKN2A, BCL2L11, and CCNG1, as well as anti-inflammatory molecules such as SOCS1 and FoxP3. Additionally, transfection studies involving miR-21 and use of Mir21 -/- mice suggested that while this miR plays a critical role in EAE, additional miRs may also be involved in THC+CBD-mediated attenuation of EAE. Collectively, this study suggests that combination of THC+CBD suppresses neuroinflammation and attenuates clinical EAE development and that this effect is associated with changes in miRNA profile in brain-infiltrating cells.

Keywords: CB1; CB2; CBD; EAE; THC; miR-21a-5p; multiple sclerosis.

Source: https://pubmed.ncbi.nlm.nih.gov/31497013/?utm_source=no_user_agent&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1TQbL92JdzYTve0m3OsSoggMby2JyZDVBLRHiDMYZkT1hs6YNQ&fc=20200804223051&ff=20200824175210&v=2.11.5

Heartland

The Role of Cannabinoids as Anticancer Agents in Pediatric Oncology

Cannabinoids are a group of chemicals that bind to receptors in the human body and, in turn, modulate the endocannabinoid system (ECS). They can be endogenously produced, synthetic, or derived from the plant Cannabis sativa L. Research over the past several decades has shown that the ECS is a cellular communication network essential to maintain multiple biological functions and the homeostasis of the body. Indeed, cannabinoids have been shown to influence a wide variety of biological effects,…

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Cannabinoids are a group of chemicals that bind to receptors in the human body and, in turn, modulate the endocannabinoid system (ECS). They can be endogenously produced, synthetic, or derived from the plant Cannabis sativa L. Research over the past several decades has shown that the ECS is a cellular communication network essential to maintain multiple biological functions and the homeostasis of the body. Indeed, cannabinoids have been shown to influence a wide variety of biological effects, including memory, pain, reproduction, bone remodeling or immunity, to name a few. Unsurprisingly, given these broad physiological effects, alterations of the ECS have been found in different diseases, including cancer. In recent years, the medical use of cannabis has been approved in different countries for a variety of human conditions. However, the use of these compounds, specifically as anticancer agents, remains controversial. Studies have shown that cannabinoids do have anticancer activity in different tumor types such as breast cancer, melanoma, lymphoma and adult brain cancer. Specifically, phytocannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) has been shown to induce apoptosis and inhibit proliferation of adult cancer cells, as well as modulate angiogenesis and metastasis. Despite increasing evidence that cannabinoids elicit antitumor effects in adult cancers, there is minimal data available on their effects in children or in pediatric cancers despite public and clinical demand for information. Here we describe a comprehensive and critical review of what is known about the effects of cannabinoids on pediatric cancers, highlight current gaps in knowledge and identify the critical issues that need addressing before considering these promising but controversial drugs for use in pediatric oncology.

Keywords: CBD; THC; cannabidiol; cannabinoid; childhood cancer; medical cannabis; pediatric oncology; Δ9-tetrahydrocannabinol.

Source: https://pubmed.ncbi.nlm.nih.gov/33466435/?utm_source=no_user_agent&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1zmroqAMnEquTZFTfdGx1V1gPEavo-Be3-FKTecJpOlB7LykCL&fc=20200804213506&ff=20210120135252&v=2.14.2

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Heartland

Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment

Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes. The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson’s disease, Tourette’s syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been…

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Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes. The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson’s disease, Tourette’s syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been proven so far, results from the affinity of these compounds predominantly for the receptors of the endocannabinoid system (the cannabinoid receptor type 1 (CB1), type two (CB2), and the G protein-coupled receptor 55 (GPR55)) but, also, for peroxisome proliferator-activated receptor (PPAR), glycine receptors, serotonin receptors (5-HT), transient receptor potential channels (TRP), and GPR, opioid receptors. The synergism of action of phytochemicals present in Cannabis sp. raw material is also expressed in their increased bioavailability and penetration through the blood-brain barrier. This review provides an overview of phytochemistry and pharmacology of compounds present in Cannabis extracts in the context of the current knowledge about their synergistic actions and the implications of clinical use in the treatment of selected diseases.

Keywords: Cannabis; multitarget; phytocannabinoids (THC and CBD); receptors; terpenes.

Source: https://pubmed.ncbi.nlm.nih.gov/33466734/?utm_source=no_user_agent&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1zmroqAMnEquTZFTfdGx1V1gPEavo-Be3-FKTecJpOlB7LykCL&fc=20200804213506&ff=20210120135252&v=2.14.2

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Pervasive cropland in protected areas highlight trade-offs between conservation and food security

Global cropland expansion over the last century caused widespread habitat loss and degradation. Establishment of protected areas aims to counteract the loss of habitats and to slow species extinctions. However, many protected areas also include high levels of habitat disturbance and conversion for uses such as cropland. Understanding where and why this occurs may realign conservation priorities and inform protected area policy in light of competing priorities such as food security. Here, we use…

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. 2021 Jan 26;118(4):e2010121118.

doi: 10.1073/pnas.2010121118.

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Varsha Vijay et al. Proc Natl Acad Sci U S A. .

Abstract

Global cropland expansion over the last century caused widespread habitat loss and degradation. Establishment of protected areas aims to counteract the loss of habitats and to slow species extinctions. However, many protected areas also include high levels of habitat disturbance and conversion for uses such as cropland. Understanding where and why this occurs may realign conservation priorities and inform protected area policy in light of competing priorities such as food security. Here, we use our global synthesis cropland dataset to quantify cropland in protected areas globally and assess their relationship to conservation aims and socio-environmental context. We estimate that cropland occupies 1.4 million km2 or 6% of global protected area. Cropland occurs across all protected area management types, with 22% occurring in strictly protected areas. Cropland inside protected areas is more prevalent in countries with higher population density, lower income inequality, and with higher agricultural suitability of protected lands. While this phenomenon is dominant in midnorthern latitudes, areas of cropland in protected areas of the tropics and subtropics may present greater trade-offs due to higher levels of both biodiversity and food insecurity. Although area-based targets are prominent in biodiversity goal-setting, our results show that they can mask persistent anthropogenic land uses detrimental to native ecosystem conservation. To ensure the long-term efficacy of protected areas, post-2020 goal setting must link aims for biodiversity and human health and improve monitoring of conservation outcomes in cropland-impacted protected areas.

Keywords: CBD; area-based targets; conservation; food security; protected areas.

Conflict of interest statement

The authors declare no competing interest.

References

    1. Klein Goldewijk K., Beusen A., Doelman J., Stehfest E.. New anthropogenic land use estimates for the holocene: HYDE 3.2. Earth Syst. Sci. Data. 2017;9:927–953.
    1. Barrett C. B.. Measuring food insecurity. Science. 2010;327:825–828.
    1. Fogel R. W.. The Escape from Hunger and Premature Death, 1700-2100: Europe, America, and the Third World. 2004.
    1. Crist E., Mora C., Engelman R.. The interaction of human population, food production, and biodiversity protection. Science. 2017;356:260–264.
    1. Pimm S. L., Vijay V.. Population, Agriculture, and Biodiversity: Problems and Prospects. 2020;365.

Source: https://pubmed.ncbi.nlm.nih.gov/33468666/?utm_source=no_user_agent&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1zmroqAMnEquTZFTfdGx1V1gPEavo-Be3-FKTecJpOlB7LykCL&fc=20200804213506&ff=20210120135252&v=2.14.2

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