WIN 55,212-2, Agonist of Cannabinoid Receptors, Prevents Amyloid β1-42 Effects on Astrocytes in Primary Culture.

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“Alzheimer´s disease (AD), a neurodegenerative illness involving synaptic dysfunction with extracellular accumulation of Aβ1-42 toxic peptide, glial activation, inflammatory response and oxidative stress, can lead to neuronal death.

Endogenous cannabinoid system is implicated in physiological and physiopathological events in central nervous system (CNS), and changes in this system are related to many human diseases, including AD…

In conclusion cannabinoid WIN 55,212-2 increases cell viability and anti-inflammatory response in cultured astrocytes. Moreover, WIN 55,212-2 increases expression of anti-oxidant Cu/Zn SOD and is able to prevent inflammation induced by Aβ1-42 in cultured astrocytes.

Further studies would be needed to assess the possible beneficial effects of cannabinoids in Alzheimer’s disease patients.”

http://www.ncbi.nlm.nih.gov/pubmed/25874692

http://www.thctotalhealthcare.com/category/alzheimers-disease-ad/

Cannabis and cardiotoxicity.

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“Cannabis is the most commonly consumed illicit drug… Despite the drug’s extreme popularity, reports of cannabis-related stroke and myocardial infarction are so rare as to still be reportable… The observation that cardiotoxicity has never been reported in cancer patients taking dronabinol, the synthetic form of THC, tends to suggest that animal studies may have overstated the cardiovascular risk,” http://www.ncbi.nlm.nih.gov/pubmed/25868498

http://www.thctotalhealthcare.com/category/cardiovascular-disease/

A role for GPR55 in human placental venous endothelial cells.

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“Endocannabinoids and their G protein-coupled receptors have been suggested to play a key role in human pregnancy, by regulating important aspects such as implantation, decidualization, placentation and labor.

G protein-coupled receptor 55 (GPR55) was previously postulated to be another cannabinoid receptor, since specific cannabinoids were shown to act independently of the classical cannabinoid receptors CB1 or CB2.

Current knowledge about GPR55 expression and function in human placenta is very limited and motivated us to evaluate human placental GPR55 expression in relation to other human peripheral tissues and to analyze spatiotemporal GPR55 expression in human placenta.

Gene expression analysis revealed low GPR55 levels in human placenta, when compared to spleen and lung, the organs showing highest GPR55 expression.

Moreover, expression analysis showed 5.8 fold increased placental GPR55 expression at term compared to first trimester. Immunohistochemistry located GPR55 solely at the fetal endothelium of first trimester and term placentas. qPCR and immunocytochemistry consistently confirmed GPR55 expression in isolated primary placental arterial and venous endothelial cells. Incubation with L-α-lysophosphatidylinositol (LPI), the specific and functional ligand for GPR55, at a concentration of 1 µM, significantly enhanced migration of venous, but not arterial endothelial cells.

LPI-enhanced migration was inhibited by the GPR55 antagonist O-1918, suggesting a role of the LPI-GPR55 axis in placental venous endothelium function.”

Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context.

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“Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis.

The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study…

Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context.”

http://www.ncbi.nlm.nih.gov/pubmed/25870539

The effect of FAAH, MAGL, and Dual FAAH/MAGL inhibition on inflammatory and colorectal distension-induced visceral pain models in Rodents.

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“Recent studies showed that the pharmacological inhibition of endocannabinoid degrading enzymes such as fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) elicit promising analgesic effects in a variety of nociceptive models without serious side effects…

The selective FAAH inhibitor and dual FAAH/MAGL inhibitors were effective in both inflammatory and mechanically evoked visceral pain, while the MAGL inhibitor elicited an analgesic effect in inflammatory, but not in distension-induced, visceral pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25869205

Negative Regulation of Leptin-induced ROS Formation by CB1 Receptor Activation in Hypothalamic Neurons.

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“The adipocyte-derived, anorectic hormone, leptin, was recently shown to owe part of its regulatory effects on appetite-regulating hypothalamic neuropeptides to the elevation of ROS levels in arcuate nucleus (ARC) neurons.

Leptin is also known to exert a negative regulation on hypothalamic endocannabinoid levels and hence on cannabinoid CB1 receptor activity.

Here we investigated the possibility of a negative regulation by CB1 receptor of leptin-mediated ROS formation in the ARC…

We conclude that CB1 activation reverses leptin-induced ROS formation, and hence possibly some of the ROS-mediated effects of the hormone, by preventing PPAR-γ inhibition by leptin, with subsequent increase of catalase activity.

This mechanism might underlie in part CB1 orexigenic actions under physiopathological conditions accompanied by elevated hypothalamic endocannabinoid levels.”

Drug repurposing and emerging adjunctive treatments for schizophrenia.

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“Schizophrenia is a frequent disorder, which substantially impairs patients’ quality of life. Moreover, the burden of illness for patients, their families and for the society, in general, is substantial.

Given the current failure of a number of mechanistically new drugs, repurposed compounds may serve as alternative and/or adjunctive agents for schizophrenic patients and for treatment refractory patients in particular. Anti-inflammatory drugs, as well as N-acetylcysteine, a precursor of the major antioxidant glutathione, hormones, glutamatergic and nicotinergic compounds, ‘nutraceuticals’ (e.g., ω-3 fatty acids) and cannabidiol, an endocannabinoid modulator, represent promising agents in this field.”

http://www.ncbi.nlm.nih.gov/pubmed/25866122

Minireview: From the Bench, Toward the Clinic: Therapeutic Opportunities for Cannabinoid Receptor Modulation.

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The effects of cannabinoids have been known for centuries and over the past several decades two G-protein coupled receptors, CB1 and CB2, have been identified that are responsible for their activity.

Endogenous lipid-derived cannabinergic agents have been found, biosynthetic and catabolic machinery characterized, and synthetic agents have been designed to modulate these receptors.

Selective agents including agonists, antagonists, inverse agonists and novel allosteric modulators targeting either CB1 or CB2 have been developed to inhibit or augment their basal tone.

As a result, the role these receptors play in human physiology and their potential therapeutic applications in disease states are being elucidated.

The CB1 receptor while ubiquitous is densely expressed in the brain and CB2 is largely found on cells of immune origin.

This minireview highlights the role of CB1 in excitotoxic assaults in the brain and its potential to limit addiction liability.

In addition, it will examine the relationship between receptor activity and stimulation of insulin release from pancreatic β-cells, insulin resistance and feeding behavior leading toward obesity.

The role of CB2 in the neuropathology of amyotrophic lateral sclerosis and in the central manifestations of chronic HIV infection potentially converges at inflammatory cell activation thereby providing an opportunity for intervention.

Lastly, CB2 modulation is discussed in the context of an experimental model of post-menopausal osteoporosis.

Achieving exquisite receptor selectivity and elucidating the mechanisms underlying receptor inhibition and activation will be essential for the development of the next generation of cannabinergic-based therapeutic agents.”

Sequence heterogeneity of cannabidiolic- and tetrahydrocannabinolic acid-synthase in Cannabis sativa L. and its relationship with chemical phenotype.

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“Sequence variants of THCA- and CBDA-synthases were isolated from different Cannabis sativa L. strains expressing various wild-type and mutant chemical phenotypes (chemotypes). Expressed and complete sequences were obtained from mature inflorescences. Each strain was shown to have a different specificity and/or ability to convert the precursor CBGA into CBDA and/or THCA type products. The comparison of the expressed sequences led to the identification of different mutations, all of them due to SNPs. These SNPs were found to relate to the cannabinoid composition of the inflorescence at maturity and are therefore proposed to have a functional significance. The amount of variation was found to be higher within the CBDAS sequence family than in the THCAS family, suggesting a more recent evolution of THCA-forming enzymes from the CBDAS group. We therefore consider CBDAS as the ancestral type of these synthases.”

http://www.ncbi.nlm.nih.gov/pubmed/25865737

Unfazed or Dazed and Confused: Does Early Adolescent Marijuana Use Cause Sustained Impairments in Attention and Academic Functioning?

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“There was no evidence indicating that adolescents who used marijuana experienced lingering attention and academic problems, relative to their pre-onset levels, after abstaining from use for at least a year.

These results suggest that adolescents who engage in low to moderate marijuana use experience an increase in observable attention and academic problems, but these problems appear to be minimal and are eliminated following sustained abstinence.”

http://www.ncbi.nlm.nih.gov/pubmed/25862212