Quantification of pain in sickle mice using facial expressions and body measurements.

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“Pain is a hallmark feature of sickle cell disease (SCD). Subjects typically quantify pain by themselves, which can be biased by other factors leading to overtreatment or under-treatment. Reliable and accurate quantification of pain, in real time, might enable to provide appropriate levels of analgesic treatment.

The mouse grimace scale (MGS), a standardized behavioral coding system with high accuracy and reliability has been used to quantify varied types of pain. We hypothesized that addition of the objective parameters of body length and back curvature will strengthen the reproducibility of MGS.

We examined MGS scores and body length and back curvature of transgenic BERK sickle and control mice following cold treatment or following treatment with analgesic cannabinoid CP55,940. We observed that sickle mice demonstrated decreased length and increased back curvature in response to cold. These observations correlate with changes in facial expression for the MGS score.

CP55,940 treatment of sickle mice showed an increase in body length and a decrease in back curvature concordant with MGS scores indicative of an analgesic effect. Thus, body parameters combined with facial expressions may provide a quantifiable unbiased method for objective measure of pain in SCD.”

http://www.ncbi.nlm.nih.gov/pubmed/26852657

http://www.thctotalhealthcare.com/category/sickle-cell-disease/

Therapeutic Potential of Cannabinoids in Psychosis.

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“Over recent years, the interest in the endocannabinoid system (ECS) as a new target for the treatment of schizophrenia has evolved.

The ECS represents one of the most relevant neurotransmitter systems in the brain and mainly fulfills a homeostatic role in terms of neurotransmission but also with respect to inflammatory processes.

Two main approaches to the modulation of endocannabinoid functioning have been chosen so far. First, the selective blockade or inverse agonism of the type 1 cannabinoid receptor has been tested for the improvement of acute psychotic symptoms, as well as for the improvement of cognitive functions in schizophrenia.

Second, the modulation of endocannabinoid levels by use of the phytocannabinoid cannabidiol and selective fatty acid amide hydrolase inhibitors has been proposed, and the antipsychotic properties of cannabidiol are currently being investigated in humans.

Unfortunately, for most of these trials that have focused on psychopathological and cognitive effects of cannabidiol, no published data are available. However, there is first evidence that cannabidiol may ameliorate psychotic symptoms with a superior side-effect profile compared with established antipsychotics.

In conclusion, several clinical trials targeting the ECS in acute schizophrenia have either been completed or are underway. Although publicly available results are currently limited, preliminary data indicate that selected compounds modulating the ECS may be effective in acute schizophrenia.

Nevertheless, so far, sample sizes of patients investigated are not sufficient to come to a final judgment, and no maintenance studies are available to ensure long-term efficacy and safety.”

http://www.ncbi.nlm.nih.gov/pubmed/26852073

http://www.thctotalhealthcare.com/category/schizophrenia/

A Lower Olfactory Capacity Is Related to Higher Circulating Concentrations of Endocannabinoid 2-Arachidonoylglycerol and Higher Body Mass Index in Women.

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“The endocannabinoid (eCB) system can promote food intake by increasing odor detection in mice.

The eCB system is over-active in human obesity.

Our aim is to measure circulating eCB concentrations and olfactory capacity in a human sample that includes people with obesity and explore the possible interaction between olfaction, obesity and the eCB system.

Our results show that obese subjects have a lower olfactory capacity than non-obese ones and that elevated fasting plasma circulating 2-AG concentrations in obesity are linked to a lower olfactory capacity.

In agreement with previous studies we show that eCBs AEA and 2-AG, and their respective congeners have a distinct profile in relation to body mass index. The present report is the first study in humans in which olfactory capacity and circulating eCB concentrations have been measured in the same subjects.”

http://www.ncbi.nlm.nih.gov/pubmed/26849214

Harvesting the biosynthetic machineries that cultivate a variety of indispensable plant natural products.

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“Plants are a sustainable resource for valuable natural chemicals best illustrated by large-scale farming centered on specific products. Here, we review recent discoveries of plant metabolic pathways producing natural products with unconventional biomolecular structures.

Prenylation of polyketides by aromatic prenyltransferases (aPTases) ties together two of the major groups of plant specialized chemicals, terpenoids and polyketides, providing a core modification leading to new bioactivities and downstream metabolic processing. Moreover, PTases that biosynthesize Z-terpenoid precursors for small molecules such as lycosantalene have recently been found in the tomato family.

Gaps in our understanding of how economically important compounds such as cannabinoids are produced are being identified using next-generation ‘omics’ to rapidly advance biochemical breakthroughs at an unprecedented rate. For instance, olivetolic acid cyclase, a polyketide synthase (PKS) co-factor from Cannabis sativa, directs the proper cyclization of a polyketide intermediate.

Elucidations of spatial and temporal arrangements of biosynthetic enzymes into metabolons, such as those used to control the efficient production of natural polymers such as rubber and defensive small molecules such as linamarin and lotaustralin, provide blueprints for engineering streamlined production of plant products.”

http://www.ncbi.nlm.nih.gov/pubmed/26851514

Cannabinoid receptor type 1 mediates high-fat diet-induced insulin resistance by increasing forkhead box O1 activity in a mouse model of obesity.

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“Hepatic glucose production is promoted by forkhead box O1 (FoxO1) under conditions of insulin resistance.

The overactivity of cannabinoid receptor type 1 (CB1R) partly causes increased liver fat deposits and metabolic dysfunction in obese rodents by decreasing mitochondrial function.

The aim of the present study was to investigate the role of FoxO1 in CB1R-mediated insulin resistance through the dysregulation of mitochondrial function in the livers of mice with high-fat diet (HFD)-induced obesity.

Taken together, our findings suggest that the anti-insulin resistance effect of AM251, which leads to an improvement of mitochondrial function in hepatic steatosis, is mediated through FoxO1.”

http://www.ncbi.nlm.nih.gov/pubmed/26847930

Anti-Inflammatory and Osteoprotective Effects of Cannabinoid-2 Receptor Agonist Hu-308 in a Rat Model of Lipopolysaccharide-Induced Periodontitis.

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“Anti-inflammatory and immunological properties of cannabinoids have been reported in several tissues.

Also, cannabinoid receptors type 2 (CB2) were reported to be expressed in osteoblast and osteoclast, suggesting a key role in bone metabolism.

The aim of the present study was to assess the effect of the treatment with the cannabinoid-2 receptor agonist HU-308 in the oral health of rats subjected to lipopolysaccharide (LPS)-induced periodontitis.

This study demonstrates the anti-inflammatory, osteoprotective and pro-homeostatic effects of HU-308 in oral tissues of rats with LPS-induced periodontitis.”

http://www.ncbi.nlm.nih.gov/pubmed/26846967

Selective Cannabinoid Receptor-1 Agonists Regulate Mast Cell Activation in an Oxazolone-Induced Atopic Dermatitis Model.

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“Many inflammatory mediators, including various cytokines (e.g. interleukins and tumor necrosis factor [TNF]), inflammatory proteases, and histamine are released following mast cell activation.

Endogenous cannabinoids such as palmitoylethanolamide (PEA) and N-arachidonoylethanolamine (anandamide or AEA), were found in peripheral tissues and have been proposed to possess autacoid activity, implying that cannabinoids may downregulate mast cell activation and local inflammation.

Our results indicate that CB1R agonists down-regulate mast cell activation and may be used for relieving inflammatory symptoms mediated by mast cell activation, such as atopic dermatitis, psoriasis, and contact dermatitis.”

http://www.ncbi.nlm.nih.gov/pubmed/26848215

Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen-induced pulmonary inflammation in mice.

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“Accumulation of activated eosinophils in tissue is a hallmark of allergic inflammation.

The endocannabinoid 2-arachidonoylglycerol (2-AG) has been proposed to elicit eosinophil migration in a CB2 receptor/Gi/o -dependent manner.

Here we explored the direct contribution of specific CB2 receptor activation to human and mouse eosinophil effector function in vitro and in vivo.

Our data indicate that CB2 may directly contribute to the pathogenesis of eosinophil-driven diseases. Moreover, we provide new insights into the molecular mechanisms underlying the CB2 -mediated priming of eosinophils. Hence, antagonism of CB2 receptors may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophilic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26850094

Medical cannabis: considerations for the anesthesiologist and pain physician.

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“New regulations are in place at the federal and provincial levels in Canada regarding the way medical cannabis is to be controlled. We present them together with guidance for the safe use of medical cannabis and recent clinical trials on cannabis and pain.

Health Canada has approved a new regulation on medical marijuana/cannabis, the Marihuana for Medical Purposes Regulations: The production of medical cannabis by individuals is illegal. Health Canada, however, has licensed authorized producers across the country, limiting the production to specific licenses of certain cannabis products. There are currently 26 authorized licensed producers from seven Canadian provinces offering more than 200 strains of marijuana.

We provide guidance for the safe use of medical cannabis.

The recent literature indicates that currently available cannabinoids are modestly effective analgesics that provide a safe, reasonable therapeutic option for managing chronic non-cancer-related pain.

The science of medical cannabis and the need for education of healthcare professionals and patients require continued effort. Although cannabinoids work to decrease pain, there is still a need to confirm these beneficial effects clinically and to exploit them with acceptable benefit-to-risk ratios.”

http://www.ncbi.nlm.nih.gov/pubmed/26850063

Cannabidiol, neuroprotection and neuropsychiatric disorders.

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“Cannabidiol (CBD) is a non-psychotomimetic phytocannabinoid derived from Cannabis sativa.

It has possible therapeutic effects over a broad range of neuropsychiatric disorders.

CBD attenuates brain damage associated with neurodegenerative and/or ischemic conditions.

It also has positive effects on attenuating psychotic-, anxiety- and depressive-like behaviors.

Moreover, CBD affects synaptic plasticity and facilitates neurogenesis.

The mechanisms of these effects are still not entirely clear but seem to involve multiple pharmacological targets.

In the present review, we summarized the main biochemical and molecular mechanisms that have been associated with the therapeutic effects of CBD, focusing on their relevance to brain function, neuroprotection and neuropsychiatric disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26845349