Palmitoylethanolamide reduces inflammation and itch in a mouse model of contact allergic dermatitis.

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“In mice, 2,4-dinitrofluorobenzene (DNFB) induces contact allergic dermatitis (CAD), which, in a late phase, is characterized by mast cell (MC) infiltration and angiogenesis.

Palmitoylethanolamide (PEA), an endogenous anti-inflammatory molecule, acts by down-modulating MCs following activation of the cannabinoid CB2 receptor and peroxisome proliferator-activated receptor-α (PPAR-α).

We have previously reported the anti-inflammatory effect of PEA in the early stage of CAD.

Here, we examined whether PEA reduces the features of the late stage of CAD including MC activation, angiogenesis and itching.

PEA, by reducing the features of late stage CAD in mice, may be beneficial in this pathological condition.”

https://www.ncbi.nlm.nih.gov/pubmed/27720681

Revealing the role of the endocannabinoid system modulators, SR141716A, URB597 and VDM-11, in sleep homeostasis.

 

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“The endocannabinoid system comprises receptors (CB1 and CB2 cannabinoid receptors), enzymes (Fatty Acid Amide Hydrolase [FAAH], which synthesizes the endocannabinoid anandamide), as well as the anandamide membrane transporter (AMT).

Importantly, previous experiments have demonstrated that the endocannabinoid system modulates multiple neurobiological functions, including sleep.

For instance, SR141716A (the CB1 cannabinoid receptor antagonist) as well as URB597 (the FAAH inhibitor) increase waking in rats whereas VDM-11 (the blocker of the AMT) enhances sleep in rodents. However, no further evidence is available regarding the neurobiological role of the endocannabinoid system in the homeostatic control of sleep.

Therefore, the aim of the current experiment was to test if SR141716A, URB597 or VDM-11 would modulate the sleep rebound after sleep deprivation. Thus, these compounds were systemically injected (5, 10, 20mg/Kg; ip; separately each one) to rats after prolonged waking. We found that SR141716A and URB597 blocked in dose-dependent fashion the sleep rebound whereas animals treated with VDM-11 displayed sleep rebound during the recovery period.

Complementary, injection after sleep deprivation of either SR141716A or URB597 enhanced dose-dependently the extracellular levels of dopamine, norepinephrine, epinephrine, serotonin, as well as adenosine while VDM-11 caused a decline in contents of these molecules.

These findings suggest that SR141716A or URB597 behave as a potent stimulants since they suppressed the sleep recovery period after prolonged waking.

It can be concluded that elements of the endocannabinoid system, such as the CB1 cannabinoid receptor, FAAH and AMT, modulate the sleep homeostasis after prolonged waking.”

https://www.ncbi.nlm.nih.gov/pubmed/27746343

Hemopressin peptides as modulators of the endocannabinoid system and their potential applications as therapeutic tools.

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“The endocannabinoid system is activated by the binding of natural arachidonic acid derivatives (endogenous cannabinoids or endocannabinoids) as lipophilic messengers to cannabinoid receptors CB1 and CB2.

The endocannabinoid system comprises also many hydrolytic enzymes responsible for the endocannabinoids cleavage, such as FAAH and MAGL. These two enzymes are possible therapeutic targets for the development of new drugs as indirect cannabinoid agonists.

Recently a new family of endocannabinoid modulators was discovered; the lead of this family is the nonapeptide hemopressin produced from enzymatic cleavage of the α-chain of hemoglobin and acting as negative allosteric modulator of CB1. Hemopressin shows several physiological effects, e.g. antinociception, hypophagy, and hypotension.  It is still matter of debate whether this peptide, isolated from the brain of rats is a real neuromodulator of the endocannabinoid system.

Recent evidence indicates that hemopressin could be a by-product formed by chemical degradation of a longer peptide RVD-hemopressin during the extraction from the brain homolysate. Indeed, RVD-hemopressin is more active than hemopressin in certain biological tests and may bind to the same subsite as Rimonabant, which is an inverse agonist for the CB1 receptor and a μ-opioid receptor antagonist.

These findings have stimulated several studies to verify this hypothesis and to evaluate possible therapeutic applications of hemopressin, its peptidic derivatives and synthetic analogues, opening new perspectives to the development of novel cannabinoid drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/27748182

Marijuana Use and Type 2 Diabetes Mellitus: a Review.

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“Marijuana is used by millions of people, with use likely to increase in the USA because of the trend towards increased decriminalization and legalization. Obesity and diabetes mellitus (DM) rates have increased dramatically in the USA over the past 30 years, with a recent estimate of 29 million individuals with DM. Because there is a plausible link between marijuana use and diabetes due to the known effects of cannabinoids on adipose tissue and glucose/insulin metabolism, it is important to study and understand how marijuana use is related to obesity and diabetes. This paper provides background on the human endocannabinoid system and studies of the association of marijuana use with body mass index/obesity, metabolic syndrome, prediabetes, and diabetes. The studies to date have shown that marijuana use is associated with either lower odds or no difference in the odds of diabetes than non-use.”

https://www.ncbi.nlm.nih.gov/pubmed/27747490

Cannabidiol Prevents Motor and Cognitive Impairments Induced by Reserpine in Rats.

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“Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa that presents antipsychotic, anxiolytic, anti-inflammatory, and neuroprotective effects.

In Parkinson’s disease patients, CBD is able to attenuate the psychotic symptoms induced by L-DOPA and to improve quality of life.

Repeated administration of reserpine in rodents induces motor impairments that are accompanied by cognitive deficits, and has been applied to model both tardive dyskinesia and Parkinson’s disease.

The present study investigated whether CBD administration would attenuate reserpine-induced motor and cognitive impairments in rats.

Our data show that CBD is able to attenuate motor and cognitive impairments induced by reserpine, suggesting the use of this compound in the pharmacotherapy of Parkinson’s disease and tardive dyskinesia.”

https://www.ncbi.nlm.nih.gov/pubmed/27733830

Central Aspects of Nausea and Vomiting in GI Disorders.

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“Nausea and vomiting result from continuous interactions among gastrointestinal, central nervous system, and autonomic nervous system. Despite being closely associated, central pathways of nausea and vomiting appear to be at least partly different and nausea is no longer considered only a penultimate step of vomiting. Although our understanding of central pathways of nausea has improved over the last one decade, it is still very basic.

Afferent pathways from gastrointestinal tract via vagus, vestibular system, and chemoreceptor trigger zone project to nucleus tractus solitarius which, in turn, relays the signal to central pattern generator initiating multiple downstream pathways. This central nausea pathway appears to be under constant modulation by autonomic nervous system and cerebral cortex.

There is also some evidence that central pathway of chronic nausea is different from that of acute nausea and closely resembles that of neuropathic pain. This improved understanding has modified the way we can approach the treatment of acute and chronic nausea.

While conventional therapies such as antiemetics (antiserotoninergic, antihistaminic, antidopaminergic) and prokinetics are commonly used to manage acute nausea, they are not as effective in improving chronic nausea.

Recently, neuromodulators such as tricyclic antidepressants, gabapentin, olanzapine, benzodiazepines, and cannabinoids have been shown to have antinausea effect.

There is a need to study the utility of these drugs in managing chronic functional nausea. Improving our understanding of central and peripheral circuitry of nausea will allow us to better utilize the currently available drugs and develop new therapeutic options.”

https://www.ncbi.nlm.nih.gov/pubmed/27734216

Association of Anandamide with altered Binocular Depth Inversion Illusion in Schizophrenia.

 

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“Binocular depth inversion illusion (BDII) represents an illusion of visual perception that involves higher-order visual and cognitive processes. Its impairment has been linked to psychotic conditions and identified as a marker for at risk mental states.

The endogenous cannabinoid system (ECS) is involved in various neurophysiological processes. One of its key components, anandamide, is involved in the pathophysiology of schizophrenia.

Little is known about its impact on BDII alterations. Therefore, we explored associations between BDII and anandamide levels.

Conclusions These findings support the hypothesis of an involvement of anandamide in cognitive processes impaired in schizophrenia and are consistent with a protective effect of elevated anandamide levels herein.”

[The endocannabinoid system and bone].

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“Recent studies suggest an important role for the skeletal endocannabinoid system in the regulation of bone mass in both physiological and pathological conditions. Both major endocannabinoids (anandamid and 2-arachidonoylglycerol), endocannabinoid receptors – CB1-receptor (CB1R) a CB2-receptor (CB2R) and the endocannabinoid metabolizing enzymes are present or expressed in osteoblasts and osteoclasts. Previous studies identified multiple risk and protective variants of CNR2 gene dealing with the relationship to bone density and/or osteoporosis. Selective CB1R/ CB2R-inverse agonists/antagonists and CB2R-inverse agonists/antagonists are candidates for prevention of bone mass loss and combined antiresorptive and anabolic therapy for osteoporosis.”

https://www.ncbi.nlm.nih.gov/pubmed/27734700

A New Study Suggests Cannabis Could Treat Cervical Cancer

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“A new study suggests that cannabis might be useful in treating cervical cancer.

Through in vitro, or test tube/petri dish, analysis, researchers from the biochemistry department at North-West University in Potchefstroom, South Africa found that the non-psychotropic cannabinoid, or chemical compound, CBD (cannabidiol), taken from a Cannabis sativa extract, could hold anticarcinogenic properties. They pointed out that cannabis acted on the cancerous cells through apoptosis, or a process of cell death, causing only the cancerous cells to kill themselves, and inhibiting their growth.

Cervical cancer is no longer a leading cause of death as much as it used to be in the United States, thanks in large part to the widespread use of pap smears, but it’s still a widespread threat. And in Sub-Saharan Africa, it kills 250,000 women every year. “This makes it the most lethal cancer amongst black women and calls for urgent therapeutic strategies,” the study’s authors wrote in the BMC Complementary and Alternative Medicine journal. “In this study we compare the anti-proliferative effects of crude extract of Cannabis sativa and its main compound cannabidiol on different cervical cancer cell lines.”

It will take much more research before cannabis can be integrated into official cervical cancer treatments in sub-Saharan Africa. But earlier studies also shows that cannabis has been useful in treating not only the symptoms of cancer and chemotherapy, but also the cancer itself.

One study from the journal of Current Clinical Pharmacology found that cannabis served as a preventative agent, reducing inflammation, which researchers also said was useful in reducing the likelihood of cancer. Another study from Oncology Hematology also noted cannabis’ anti-cancer effects, explaining how the plant’s cannabinoids inhibited tumor growth in vitro, such as in a petri dish or test tube, and in vivo, or a living organism.

A handful of other studies have also looked into cannabis as a treatment specifically for cervical cancer. Another from the University Hospital in Geneva, Switzerland, found that the cannabinoids, including the body’s own endocannabinoids, offered “attractive opportunities for the development of novel potent anticancer drugs.”

With that said, often medical marijuana is ingested via capsules, tinctures, vaporizable oils, and other non-smokeable, more pharmaceutical-style forms. Should cannabis eventually become approved for cervical cancer treatment in Africa, it may be up for debate whether whole plant therapy (in which all the cannabinoids work synergistically through the “entourage effect”) or specific cannabinoid therapy is best.”

http://motherboard.vice.com/read/a-new-study-suggests-cannabis-could-treat-cervical-cancer

Cannabinoids Inhibit Glioma Cell Invasion by Down-regulating Matrix Metalloproteinase-2 Expression

Cancer Research: 68 (6)

“Cannabinoids, the active components of Cannabis sativa L. and their derivatives, inhibit tumor growth in laboratory animals by inducing apoptosis of tumor cells and impairing tumor angiogenesis.

It has also been reported that these compounds inhibit tumor cell spreading.

Here, we evaluated the effect of cannabinoids on matrix metalloproteinase (MMP) expression and its effect on tumor cell invasion.

Local administration of Δ9-tetrahydrocannabinol (THC), the major active ingredient of cannabis, down-regulated MMP-2 expression in gliomas generated in mice.

This cannabinoid-induced inhibition of MMP-2 expression in gliomas.

As MMP-2 up-regulation is associated with high progression and poor prognosis of gliomas and many other tumors, MMP-2 down-regulation constitutes a new hallmark of cannabinoid antitumoral activity.

As selective CB2 receptor activation to mice has been shown to inhibit the growth and angiogenesis of gliomas, skin carcinomas and melanomas, our observations further support the possibility of finding cannabinoid-based antitumoral strategies devoid of nondesired psychotropic side effects.”

http://cancerres.aacrjournals.org/content/68/6/1945