Cannabinoid CB1 receptors in the dorsal hippocampus and prelimbic medial prefrontal cortex modulate anxiety-like behavior in rats: additional evidence.

“Endocannabinoids (ECBs) such as anandamide (AEA) act by activating cannabinoid type 1 (CB1) or 2 (CB2) receptors. The anxiolytic effect of drugs that facilitate ECB effects is associated with increase in AEA levels in several encephalic areas, including the prefrontal cortex (PFC).

Activation of CB1 receptors by CB1 agonists injected directly into these areas is usually anxiolytic.

However, depending on the encephalic region being investigated and on the stressful experiences, opposite effects were observed, as reported in the ventral HIP. In addition, contradictory results have been reported after CB1 activation in the dorsal HIP (dHIP).

Therefore, in the present paper we have attempted to verify if directly interfering with ECB metabolism/reuptake in the prelimbic (PL) portion of the medial PFC (MPFC) and dHIP would produce different effects in two conceptually distinct animal models: the elevated plus maze (EPM) and the Vogel conflict test (VCT).

We observed drugs which interfere with ECB reuptake/metabolism in both the PL and in the dentate gyrus of the dHIP induced anxiolytic-like effect, in both the EPM and in the VCT via CB1 receptors, suggesting CB1 signaling in these brain regions modulate defensive responses to both innate and learned threatening stimuli.

This data further strengthens previous results indicating modulation of hippocampal and MPFC activity via CB1 by ECBs, which could be therapeutically targeted to treat anxiety disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/25595265

http://www.thctotalhealthcare.com/category/anxiety-2/

Two non-psychoactive cannabinoids reduce intra-cellular lipid levels and inhibit hepatosteatosis.

“Obesity and associated metabolic syndrome have quickly become a pandemic and a major detriment to human health globally.

The presence of non-alcoholic fatty liver disease (NAFLD; hepatosteatosis) in obesity has been linked to the worsening of the metabolic syndrome, including the development of insulin resistance and cardiovascular disease. Currently, there are few options to treat NAFLD, including life style changes and insulin sensitizers.

Recent evidence suggests that the cannabinoids Δ9-tetrahydrocannabivarin (THCV) and cannabidiol (CBD) improve insulin sensitivity; we aimed at studying their effects on lipid levels…

THCV and CBD directly reduce accumulated lipid levels in vitro in a hepatosteatosis model and adipocytes.

…these cannabinoids are able to increase yolk lipid mobilization and inhibit the development of hepatosteatosis respectively.

CONCLUSIONS:

Our results suggest that THCV and CBD might be used as new therapeutic agents for the pharmacological treatment of obesity- and metabolic syndrome-related NAFLD/hepatosteatosis.”

http://www.ncbi.nlm.nih.gov/pubmed/25595882

http://www.thctotalhealthcare.com/category/obesity-2/

Endocannabinoid-mediated modulation of Gq/11 protein-coupled receptor signaling-induced vasoconstriction and hypertension.

“Activation of G protein-coupled receptors (GPCRs) can induce vasoconstriction via calcium signal-mediated and Rho-dependent pathways…

Our aim was to provide evidence that GPCR signaling-induced 2-AG production and activation of vascular type1 cannabinoid receptors (CB1R) is capable of reducing agonist-induced vasoconstriction and hypertension…

Pharmacological or genetic loss of CB1R function augmented AngII-induced blood pressure rise in mice.

These data demonstrate that vasoconstrictor effect of GPCR agonists is attenuated via Gq/11-mediated vascular endocannabinoid formation.

Agonist-induced endocannabinoid-mediated CB1R activation is a significant physiological modulator of vascular tone.

Thus, the selective modulation of GPCR signaling-induced endocannabinoid release has a therapeutic potential in case of increased vascular tone and hypertension.”

http://www.ncbi.nlm.nih.gov/pubmed/25595485

http://www.thctotalhealthcare.com/category/hypertension-high-blood-pressure/

Medical marijuana for cancer.

“Marijuana has been used for centuries, and interest in its medicinal properties has been increasing in recent years. Investigations into these medicinal properties has led to the development of cannabinoid pharmaceuticals such as dronabinol, nabilone, and nabiximols.

Dronabinol is best studied in the treatment of nausea secondary to cancer chemotherapy and anorexia associated with weight loss in patients with acquired immune deficiency syndrome, and is approved by the US Food and Drug Administration for those indications.

Nabilone has been best studied for the treatment of nausea secondary to cancer chemotherapy. There are also limited studies of these drugs for other conditions.

Nabiximols is only available in the United States through clinical trials, but is used in Canada and the United Kingdom for the treatment of spasticity secondary to multiple sclerosis and pain.

Studies of marijuana have concentrated on nausea, appetite, and pain.

This article will review the literature regarding the medical use of marijuana and these cannabinoid pharmaceuticals (with emphasis on indications relevant to oncology)”

http://www.ncbi.nlm.nih.gov/pubmed/25503438

“Both cannabis and cannabinoid pharmaceuticals can be helpful for a number of problems, including many affecting patients with cancer… given the limitations inherent in using oral medications to treat nausea and vomiting, inhalation of marijuana or a cannabinoid may be better than oral ingestion in treating this condition.” http://onlinelibrary.wiley.com/doi/10.3322/caac.21260/full

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

Association Between Marijuana Exposure and Pulmonary Function over 20 Years

TU Dublin Kevin St Library: New: American Medical Association journals (JAMA)  collection now available via IReL“Occasional and low cumulative marijuana use was not associated with adverse effects on pulmonary function.

Marijuana may have beneficial effects on pain control, appetite, mood, and management of other chronic symptoms.

Our findings suggest that occasional use of marijuana for these or other purposes may not be associated with adverse consequences on pulmonary function.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3840897/

https://jamanetwork.com/journals/jama/fullarticle/1104848

“A common misconception about medical marijuana is that if inhaled, it will have detrimental effects on the patient’s lungs. However, according to a 2012 study published in the Journal of the American Medical Association (JAMA), this notion is simply untrue; in fact, this study points to an idea quite the opposite: that medical marijuana just might improve lung health under certain conditions.” HTTPS://AGRIMEDINDUSTRIES.COM/2018/06/08/STUDY-SHOWS-MARIJUANA-HAS-A-POSITIVE-IMPACT-ON-LUNG-HEALTH-UNDER-CERTAIN-CONDITIONS/

Perturbations of the endocannabinoid system in mantle cell lymphoma: correlations to clinical and pathological features.

“The cannabinoid receptors are upregulated in many types of cancers, including mantle cell lymphoma (MCL) and have been suggested to constitute novel therapeutic targets.

…  the relative expression of the anandamide synthesizing and metabolizing enzymes in MCL is heavily perturbed.

This finding, together with high expression of cannabinoid receptors, could favor enhanced anandamide signaling and suggest that targeting the endocannabinoid system might be considered as part of lymphoma therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/25594062

“We have previously shown that exposure of MCL cells to cannabinoids induces cell death in vitro and reduces tumor growth in xenograft mouse models… cancer tissues express higher levels of cannabinoid receptors than the non-malignant counterparts and the endocannabinoid system is therefore considered as a potential novel therapeutic target in cancer therapy.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278325/

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

Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma.

“Glioblastoma (GBM) resistance to therapy is the most common cause of tumor recurrence, which is ultimately fatal in 90% of the patients 5 years after initial diagnosis. A sub-population of tumor cells with stem-like properties, glioma stem cells (GSCs), is specifically endowed to resist or adapt to the standard therapies, leading to therapeutic resistance.

Several anticancer agents, collectively termed redox therapeutics, act by increasing intracellular levels of reactive oxygen species (ROS).

In this study, we investigated mechanisms underlying GSC response and resistance to cannabidiol (CBD), a non-toxic, non-psychoactive cannabinoid and redox modulator.

…we demonstrated that combining CBD treatment with the inhibition of system Xc resulted in synergistic ROS increase leading to robust antitumor effects, that is, decreased GSC survival, self-renewal, and invasion.

Our investigation provides novel mechanistic insights into the antitumor activity of redox therapeutics and suggests that combinatorial approaches using small molecule modulators of ROS offer therapeutic benefits in GBM.”

http://www.ncbi.nlm.nih.gov/pubmed/25590811

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

 

 

Regulation of circulating endocannabinoids associated with cancer and metastases in mice and humans.

“Endocannabinoids may modify cancer development, progression and associated pain.

We determined whether cancer-evoked dysregulations in this system become manifest in altered tissue and plasma endocannabinoids…

 The endocannabinoid system was subject to cancer-associated regulations to an extent that led to measurable changes in circulating endocannabinoid levels, emphasizing the importance of the endocannabinoid system in the pathophysiology of cancer.”