Exocannabinoids effect on in vitro bovine oocyte maturation via activation of AKT and ERK1/2.

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“Endocannabinoids are known to mediate practically all reproductive events in mammals; however, little is known about their role in oocyte maturation. Through RT-PCR and immunocytochemistry, this study confirms the presence of CB1 and CB2 cannabinoidreceptors in bovine oocytes and shows how exposure to the exogenous cannabinoids HU-210 and THC during their in vitro maturation (IVM) activates the phosphorylation of AKT and ERK1/2 proteins associated with the resumption of meiosis. Although supplementation with HU-210 or THC during IVM did not increase blastocyst yields, the expression of interferon tau (IFNτ) and gap junction alpha-1 protein (GJA1) was enhanced at the blastocyst stage. Our data suggest that cannabinoid agonists may be useful IVM supplements as their presence during oocyte maturation upregulates the expression in blastocysts of key genes for embryo quality.”

https://www.ncbi.nlm.nih.gov/pubmed/27798282

Role of cannabis in digestive disorders.

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“Cannabis sativa, a subspecies of the Cannabis plant, contains aromatic hydrocarbon compounds called cannabinoids.

Tetrahydrocannabinol is the most abundant cannabinoid and is the main psychotropic constituent.

Cannabinoids activate two types of G-protein-coupled cannabinoid receptors: cannabinoid type 1 receptor and cannabinoid type 2 receptor.

There has been ongoing interest and development in research to explore the therapeutic potential of cannabis. Tetrahydrocannabinol exerts biological functions on the gastrointestinal (GI) tract.

Cannabis has been used for the treatment of GI disorders such as abdominal pain and diarrhea.

The endocannabinoid system (i.e. endogenous circulating cannabinoids) performs protective activities in the GI tract and presents a promising therapeutic target against various GI conditions such as inflammatory bowel disease (especially Crohn’s disease), irritable bowel syndrome, and secretion and motility-related disorders.

The present review sheds light on the role of cannabis in the gut, liver, and pancreas and also on other GI symptoms, such as nausea and vomiting, cannabinoid hyperemesis syndrome, anorexia, weight loss, and chronic abdominal pain.

Although the current literature supports the use of marijuana for the treatment of digestive disorders, the clinical efficacy of cannabis and its constituents for various GI disorders remains unclear.”

https://www.ncbi.nlm.nih.gov/pubmed/27792038

Cannabis improves night vision: a case study of dark adaptometry and scotopic sensitivity in kif smokers of the Rif mountains of northern Morocco.

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“Previous reports have documented an improvement in night vision among Jamaican fishermen after ingestion of a crude tincture of herbal cannabis, while two members of this group noted that Moroccan fishermen and mountain dwellers observe an analogous improvement after smoking kif, sifted Cannabis sativa mixed with tobacco (Nicotiana rustica).

Field-testing of night vision has become possible with a portable device, the LKC Technologies Scotopic Sensitivity Tester-1 (SST-1).

This study examines the results of double-blinded graduated THC administration 0-20 mg (as Marinol) versus placebo in one subject on measures of dark adaptometry and scotopic sensitivity.  Analogous field studies were performed in Morocco with the SST-1 in three subjects before and after smoking kif.

In both test situations, improvements in night vision measures were noted after THC or cannabis. It is believed that this effect is dose-dependent and cannabinoid-mediated at the retinal level.

Further testing may assess possible clinical application of these results in retinitis pigmentosa or other conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/15182912

Overlapping molecular pathways between cannabinoid receptors type 1 and 2 and estrogens/androgens on the periphery and their involvement in the pathogenesis of common diseases (Review).

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“The physiological and pathophysiological roles of sex hormones have been well documented and the modulation of their effects is applicable in many current treatments.

On the other hand, the physiological role of endocannabinoids is not yet clearly understood and the endocannabinoid system is considered a relatively new therapeutic target.

The physiological association between sex hormones and cannabinoids has been investigated in several studies; however, its involvement in the pathophysiology of common human diseases has been studied separately.

Herein, we present the first systematic review of molecular pathways that are influenced by both the cannabinoids and sex hormones, including adenylate cyclase and protein kinase A, epidermal growth factor receptor, cyclic adenosine monophosphate response element-binding protein, vascular endothelial growth factor, proto-oncogene serine/threonine-protein kinase, mitogen-activated protein kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, C-Jun N-terminal kinase and extracellular-signal-regulated kinases 1/2.

Most of these influence cell proliferative activity.

Better insight into this association may prove to be beneficial for the development of novel pharmacological treatment strategies for many common diseases, including breast cancer, endometrial cancer, prostate cancer, osteoporosis and atherosclerosis.

The associations between cannabinoids, estrogens and androgens under these conditions are also presented and the molecular interactions are highlighted.”

Splendor in the Grass? A Pilot Study Assessing the Impact of Medical Marijuana on Executive Function

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“To date, few studies have investigated the potential impact of MMJ use on cognitive performance, despite a well-documented association between recreational marijuana (MJ) use and executive dysfunction. The current study assessed the impact of 3 months of MMJ treatment on executive function, exploring whether MMJ patients would experience improvement in cognitive functioning, perhaps related to primary symptom alleviation.

Results suggest that in general, MMJ patients experienced some improvement on measures of executive functioning, including the Stroop Color Word Test and Trail Making Test, mostly reflected as increased speed in completing tasks without a loss of accuracy.

On self-report questionnaires, patients also indicated moderate improvements in clinical state, including reduced sleep disturbance, decreased symptoms of depression, attenuated impulsivity, and positive changes in some aspects of quality of life. Additionally, patients reported a notable decrease in their use of conventional pharmaceutical agents from baseline, with opiate use declining more than 42%.

Data from the current investigation provide preliminary evidence that after 3 months of treatment, MMJ users did not experience executive functioning deficits, which are often observed in regular, recreational MJ users. In fact, MMJ patients evidenced improvement in certain aspects of performance on these measures, particularly with regard to time required to complete tasks.”

http://journal.frontiersin.org/article/10.3389/fphar.2016.00355/full

Effect of cannabis smoking on lung function and respiratory symptoms: a structured literature review.

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“As cannabis use increases, physicians need to be familiar with the effects of both cannabis and tobacco on the lungs. However, there have been very few long-term studies of cannabis smoking, mostly due to legality issues and the confounding effects of tobacco.

It was previously thought that cannabis and tobacco had similar long-term effects as both cause chronic bronchitis. However, recent large studies have shown that, instead of reducing forced expiratory volume in 1 s and forced vital capacity (FVC), marijuana smoking is associated with increased FVC.

The cause of this is unclear, but acute bronchodilator and anti-inflammatory effects of cannabis may be relevant.”

https://www.ncbi.nlm.nih.gov/pubmed/27763599

Cannabinoid Receptor 2 Activation Restricts Fibrosis and Alleviates Hydrocephalus after Intraventricular Hemorrhage.

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“Fibrosis in ventricular system has a role in hydrocephalus following intraventricular hemorrhage (IVH).

The cannabinoid receptor 2 (CB2) has been reported to participate in alleviating the fibrosis process of many diseases.

However, its role in fibrosis after IVH was unclear so far, and we hypothesized that CB2 activation has potential to attenuate hydrocephalus after IVH via restricting fibrosis. So the present study was designed to investigate this hypothesis in a modified rat IVH model.

In conclusion, CB2 may have anti-fibrogenic effects after IVH. CB2 agonist suppressed fibrosis of ventricular system and alleviated hydrocephalus following IVH, which is partly mediated by inhibiting TGF-β1.”

https://www.ncbi.nlm.nih.gov/pubmed/27769788

Crystal Structure of the Human Cannabinoid Receptor CB1.

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“Cannabinoid receptor 1 (CB1) is the principal target of Δ9-tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use.

CB1 is activated by endocannabinoids and is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders.

Here, we present the 2.8 Å crystal structure of human CB1 in complex with AM6538, a stabilizing antagonist, synthesized and characterized for this structural study.

The structure of the CB1-AM6538 complex reveals key features of the receptor and critical interactions for antagonist binding.

In combination with functional studies and molecular modeling, the structure provides insight into the binding mode of naturally occurring CB1 ligands, such as THC, and synthetic cannabinoids.

This enhances our understanding of the molecular basis for the physiological functions of CB1 and provides new opportunities for the design of next-generation CB1-targeting pharmaceuticals.”

https://www.ncbi.nlm.nih.gov/pubmed/27768894

Therapeutic potential of fatty acid amide hydrolase, monoacylglycerol lipase, and N-acylethanolamine acid amidase inhibitors.

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“Fatty acid ethanolamides (FAEs) and endocannabinoids (ECs) have been shown to alleviate pain and inflammation, regulate motility and appetite, and produce anti-cancer, anxiolytic, and neuroprotective efficacies via cannabinoid receptor type 1 (CB1) or type 2 (CB2), or via peroxisome proliferator-activated receptor α (PPAR-α) stimulation.

FAEs and ECs are synthesized by a series of endogenous enzymes, including N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD), diacylglycerol lipase (DAGL), or phospholipase C (PLC), and their metabolism is mediated by several metabolic enzymes, including fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), N-acylethanolamine acid amidase (NAAA), or cyclooxygenase-2 (COX-2).

Over the last decades, increasing the concentration of FAEs and ECs through the inhibition of degrading enzymes has been considered to be a viable therapeutic approach to enhance their anti-nociceptive and anti-inflammatory effects, as well as protecting the nervous system.”

Structure of primary cannabinoid receptor is revealed

“Findings give insight into designing safe and effective cannabinoid medications.”

Illustration of the CB1 receptor.

“New research is providing a more detailed view into the structure of the human cannabinoid (CB1) receptor. These findings provide key insights into how natural and synthetic cannabinoids including tetrahydrocannabinol (THC)—a primary chemical in marijuana—bind at the CB1 receptor to produce their effects. The research was funded by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health.”

https://www.nih.gov/news-events/news-releases/structure-primary-cannabinoid-receptor-revealed

“‘Marijuana receptor’ uncovered in new study”  http://www.medicalnewstoday.com/articles/313564.php