Tag Archives: cannabinoid receptors

The cannabinoid receptor agonist WIN55.212 reduces consequences of status epilepticus in rats.

Posted on by
Reply

Image result for neuroscience journal logo

“An acute brain insult can cause a spectrum of primary and secondary pathologies including increased risk for epilepsy, mortality and neurodegeneration.

The endocannabinoid system, involved in protecting the brain against network hyperexcitability and excitotoxicity, is profoundly dysregulated by acute brain insults.

We hypothesize that post-insult dysregulation of the endocannabinoid signaling may contribute to deleterious effects of an acute brain injury and potentiation of endocannabinoid transmission soon after an insult may reduce its pathological outcomes.

Thus, a brief pharmacological stimulation of the endocannabinoid system soon after a brain insult exerts beneficial effects on its pathological outcome though does not prevent epileptogenesis.”

https://www.ncbi.nlm.nih.gov/pubmed/27520083

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

Posted on by
Reply

Image result for reproduction journal

“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.

Posted on by
Reply

Image result for European Journal of Gastroenterology & Hepatology

“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

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).

Posted on by
Reply

Image result for Int J Mol Med.

“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.”

 https://www.ncbi.nlm.nih.gov/pubmed/27779654

Cannabinoid derivatives exert a potent anti-myeloma activity both in vitro and in vivo.

Posted on by
Reply

Image result for Int J Cancer.

“Although hematopoietic and immune system show high levels of the cannabinoid receptor CB2, the potential effect of cannabinoids on hematologic malignancies has been poorly determined.

Here we have investigated their anti-tumor effect in multiple myeloma (MM).

We demonstrate that cannabinoids induce a selective apoptosis in MM cell lines and in primary plasma cells of MM patients, while sparing normal cells from healthy donors, including hematopoietic stem cells.

Remarkably, blockage of the CB2 receptor also inhibited cannabinoid-induced apoptosis.

Cannabinoid derivative WIN-55 enhanced the anti-myeloma activity of dexamethasone and melphalan overcoming resistance to melphalan in vitro. Finally, administration of cannabinoid WIN-55 to plasmacytoma-bearing mice significantly suppressed tumor growth in vivo.

Together, our data suggest that cannabinoids may be considered as potential therapeutic agents in the treatment of MM.”

https://www.ncbi.nlm.nih.gov/pubmed/27778331

http://www.thctotalhealthcare.com/category/multiple-myeloma/

Preclinical and Clinical Assessment of Cannabinoids as Anti-Cancer Agents.

Posted on by
Reply

Image result for Front Pharmacol.

“Cancer is the second leading cause of death in the United States with 1.7 million new cases estimated to be diagnosed in 2016. This disease remains a formidable clinical challenge and represents a substantial financial burden to the US health care system. Therefore, research and development of novel therapeutics for the treatment of cancer is of high priority.

Cannabinoids and their derivatives have been utilized for their medicinal and therapeutic properties throughout history.

Cannabinoid activity is regulated by the endocannabinoid system (ECS), which is comprised of cannabinoid receptors, transporters, and enzymes involved in cannabinoid synthesis and breakdown.

More recently, cannabinoids have gained special attention for their role in cancer cell proliferation and death. However, many studies investigated these effects using in vitro models which may not adequately mimic tumor growth and metastasis.

As such, this article aims to review study results which evaluated effects of cannabinoids from plant, synthetic and endogenous origins on cancer development in preclinical animal models and to examine the current standing of cannabinoids that are being tested in human cancer patients.” https://www.ncbi.nlm.nih.gov/pubmed/27774065

“The studies reviewed herein indicate that cannabinoids elicit activity through cannabinoid receptor dependent and independent pathways. The evidence generated in these human studies are still informative and, when taken together with the strong in vivo animal data demonstrating anti-tumor effects of cannabinoids, offer promise for a clinical role for cannabinoids in the eradication of tumors. Hence, these investigations shed light on the role of cannabinoids on tumor growth in vivo and may ultimately pave the way for the development of novel cannabinoid therapeutics for cancer treatment.”  http://journal.frontiersin.org/article/10.3389/fphar.2016.00361/full

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

Posted on by
Reply

Image result for brain research journal

“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

Targeting cannabinoid receptor-2 pathway by phenylacetylamide suppresses the proliferation of human myeloma cells through mitotic dysregulation and cytoskeleton disruption.

Posted on by
Reply

Image result for molecular carcinogenesis journal

“Cannabinoid receptor-2 (CB2) is expressed dominantly in the immune system, especially on plasma cells.

Cannabinergic ligands with CB2 selectivity emerge as a class of promising agents to treat CB2-expressing malignancies without psychotropic concerns.

In this study, we found that CB2 but not CB1 was highly expressed in human multiple myeloma (MM) and primary CD138+ cells.

Thus, targeting CB2 may represent an attractive approach to treat cancers of immune origin.”

https://www.ncbi.nlm.nih.gov/pubmed/25640641

The effects of cannabidiol and its synergism with bortezomib in multiple myeloma cell lines. A role for transient receptor potential vanilloid type-2.

Posted on by
Reply

Image result for Int J Cancer

“Multiple myeloma (MM) is a plasma cell (PC) malignancy characterised by the accumulation of a monoclonal PC population in the bone marrow (BM).

Cannabidiol (CBD) is a non-psychoactive cannabinoid with antitumoural activities, and the transient receptor potential vanilloid type-2 (TRPV2) channel has been reported as a potential CBD receptor.

TRPV2 activation by CBD decreases proliferation and increases susceptibility to drug-induced cell death in human cancer cells.

However, no functional role has been ascribed to CBD and TRPV2 in MM. In this study, we identified the presence of heterogeneous CD138+TRPV2+ and CD138+TRPV2- PC populations in MM patients, whereas only the CD138+ TRPV2- population was present in RPMI8226 and U266 MM cell lines.

Because bortezomib (BORT) is commonly used in MM treatment, we investigated the effects of CBD and BORT in CD138+TRPV2- MM cells and in MM cell lines transfected with TRPV2 (CD138+TRPV2+).

These results showed that CBD by itself or in synergy with BORT strongly inhibited growth, arrested cell cycle progression and induced MM cells death by regulating the ERK, AKT and NF-κB pathways with major effects in TRPV2+ cells.

These data provide a rationale for using CBD to increase the activity of proteasome inhibitors in MM.”

https://www.ncbi.nlm.nih.gov/pubmed/24293211

Crystal Structure of the Human Cannabinoid Receptor CB1.

Posted on by
Reply

Image result for cell journal

“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