Spontaneous Cannabinoid Receptor 2 (CB2) Expression in the Cochlea of Adult Albino Rat and Its Up-Regulation after Cisplatin Treatment

Posted on September 8, 2016 by David

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“We provide evidence for the presence of cannabinoid CB₂ receptors in some cellular types of the cochlea of the adult albino rat. Cannabinoids and their receptors are increasingly being studied because of their high potential for clinical use. As a hyperspecialized portion of the peripheral nervous system, study of the expression and function of cannabinoid receptors in the hearing organ is of high interest. Stria vascularis and inner hair cells express CB₂ receptor, as well as neurites and cell bodies of the spiral ganglion. Cellular types such as supporting cells and outer hair cells, in which the expression of other types of functional receptors has been reported, do not significantly express CB₂ receptors in this study. An up-regulation of CB₂ gene expression was detected after an ototoxic event such as cisplatin treatment, probably due to pro-inflammatory events triggered by the drug. That fact suggests promising potential of CB₂receptor as a therapeutic target for new treatments to palliate cisplatin-induced hearing loss and other ototoxic events which triggers inflammatory pathways.” http://www.ncbi.nlm.nih.gov/pubmed/27564061

“In conclusion, evidence for the presence of cannabinoid CB₂ receptor by immunohystochemistry and by RT-qPCR was provided. An immunolabeling of CB₂ antibodies in four structures of the adult rat cochlea was found. That was, stria vascularis, inner hair cells, auditory afferent nerves and cell bodies of the spiral ganglion. Up-regulation of CB₂ gene expression in animals exposed to CDDP treatment was also detected, when compared with healthy animals. This fact was partially supported by the higher immunofluorescence observed in the stria vascularis of CDDP-treated animals if compared with the healthy ones. These results suggest a considerable promising potential of CB₂ receptor as a target of new treatments against CDDP-induced ototoxicity, and probably against other inflammatory diseases in the inner ear. Further research is needed to determine the functionality of CB₂receptors in the organ of Corti and the potential therapeutic role of agonists and antagonists of these receptors.” http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161954

“Study: Cannabinoids a Potential Treatment Option for Chemotherapy-Induced Hearing Loss” http://www.theweedblog.com/study-cannabinoids-potential-treatment-option-chemotherapy-induced-hearing-loss/

Modulation of Long-Term Potentiation of Cortico-Amygdala Synaptic Responses and Auditory Fear Memory by Dietary Polyunsaturated Fatty Acid.

Posted on September 8, 2016 by David

“Converging evidence suggests that an imbalance of ω3 to ω6 polyunsaturated fatty acid (PUFA) in the brain is involved in mental illnesses such as anxiety disorders.

We previously reported that the dietary ratio of ω3 to ω6 PUFA alters this ratio in the brain, and influences contextual fear memory.

In addition to behavioral change, enhancement of cannabinoid CB1 receptor-mediated short-term synaptic plasticity and facilitation of the agonist sensitivity of CB1 receptors have been observed in excitatory synaptic responses in the basolateral nucleus of the amygdala (BLA).

These results suggest that the balance of ω3 to ω6 PUFA has an impact on fear memory and cortico-amygdala synaptic plasticity, both in a CB1 receptor-dependent manner.”

http://www.ncbi.nlm.nih.gov/pubmed/27601985

[Progress in study on endocannabinoids and cannabinoid receptors in the treatment for neuropathic pain].

Posted on September 8, 2016 by David

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“Endocannabinoids and cannabinoid receptors are expressed in various central pain modulation regions. They maintain in dynamic changes in the expression level and distribution under different pathological and physiological conditions. These changes possess advantage as well as disadvantage. Exogenous administration of endocannabinoids exerts analgesic effect in different pain models, which is mainly mediated by the cannabinoid CB1 and CB2 receptors. Inhibition of enzymes for degrading endocannabinoids in different pain models also shows analgesic effect due to the increased local levels of endocannabinoids.”

http://www.ncbi.nlm.nih.gov/pubmed/27600019

Selective modulator of cannabinoid receptor type 2 (CB2) against biochemical alterations and brain damage in chronic cerebral hypoperfusion induced vascular dementia.

Posted on September 8, 2016 by David

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“Vascular dementia is the second most common cause of cognitive decline in aged people but the effectual therapeutic target is still missing.

Chronic cerebral hypoperfusion (CCH) has been widely found in vascular dementia (VaD) patients. CCH is thought to link with neurodegenerative disorders and their subsequent cognitive impairment.

The present study has been framed to investigate the role of selective agonist of CB2 receptor (1-phenylisatin) in CCH induced VaD.

These results indicate that 2VO induced CCH in rats, which was attenuated with the treatment of 1-phenylisatin.

Hence, it may be suggested that modulation in cannabinoid receptor may provide benefits in CCH as cognitive impairment and VaD.

Therefore, pharmacological positive modulation of CB2 receptors may be a potential research target for alleviation of VaD.”

http://www.ncbi.nlm.nih.gov/pubmed/27599483

Cannabidiol and Epilepsy: Sifting, Winnowing and Buzz

Posted on September 7, 2016 by David

“Over the past few years there has been a phenomenal resurgence in the interest in the use of Cannabis sativa and Cannabis indica for the treatment of epilepsy (among many other disorders as well). Clearly, the media and the proliferation of internet sites offering advice has fueled interest not only among patients and caregivers, but clinicians as well. Mainstream and social media interest in patient testimonials have, for better or worse, created a great deal of buzz. First, to the answer of does CBD provide benefit, the answer appears to be yes. With respect to safety perspective, CBD seemed to be well tolerated in most patients. At least we can finally say with some confidence to our patients, their families, and our colleagues, that there is more to this drug than media hype, and internet buzz.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4988076/

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

Successful Treatment of Suspected Cannabinoid Hyperemesis Syndrome Using Haloperidol in the Outpatient Setting.

Posted on September 7, 2016 by David

“Chronic use of cannabis can result in a syndrome of hyperemesis characterized by cyclical vomiting without any other identifiable causes. Cannabinoid hyperemesis syndrome (CHS) is seldom responsive to traditional antiemetic therapies. Despite frequent nausea and vomiting, patients may be reluctant to discontinue use of cannabis. We report a case of severe, refractory CHS with complete resolution of nausea and vomiting after treatment with haloperidol in the outpatient setting. After review of the literature, we believe this is the first reported successful outpatient treatment of CHS and suggests a potential treatment for refractory patients.”

http://www.ncbi.nlm.nih.gov/pubmed/27597918

“Haloperidol, marketed under the trade name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, nausea and vomiting, delirium, agitation, acutepsychosis, and hallucinations in alcohol withdrawal. It may be used by mouth, as an injection into a muscle, or intravenously.” https://en.wikipedia.org/wiki/Haloperidol

“Is haloperidol the wonder drug for cannabinoid hyperemesis syndrome? The present report highlights the use of haloperidol as an agent that successfully and safely treats the unrelenting symptoms of CHS.” https://www.ncbi.nlm.nih.gov/pubmed/28052951

“Successful Treatment of Cannabinoid Hyperemesis Syndrome with Topical Capsaicin.” https://www.ncbi.nlm.nih.gov/pubmed/29379817

“Capsaicin (/kæpˈseɪ.ɪsɪn/ (INN); 8-methyl-N-vanillyl-6-nonenamide) is an active component of chili peppers, which are plants belonging to the genus Capsicum.” https://en.wikipedia.org/wiki/Capsaicin

Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation.

Posted on September 7, 2016 by David

“Since the discovery of the endocannabinoid system consisting of cannabinoid receptors, endogenous ligands, and biosynthetic and metabolizing enzymes, interest has been renewed in investigating the promise of cannabinoids as therapeutic agents.

Abundant evidence indicates that cannabinoids modulate immune responses.

An inflammatory response is triggered when innate immune cells receive a danger signal provided by pathogen- or damage-associated molecular patterns engaging pattern-recognition receptors.

Toll-like receptor family members are prominent pattern-recognition receptors expressed on innate immune cells.

Cannabinoids suppress Toll-like receptor-mediated inflammatory responses.

Innate immune cells express cannabinoid receptors and produce endogenous cannabinoids.

Hence, innate immune cells may play a role in regulating endocannabinoid homeostasis, and, in turn, the endocannabinoid system modulates local inflammatory responses.

Studies designed to probe the interaction between the innate immune system and the endocannabinoid system may identify new potential molecular targets in developing therapeutic strategies for chronic inflammatory diseases.

This review discusses the endocannabinoid system and Toll-like receptor family and evaluates the interaction between them.”

http://www.ncbi.nlm.nih.gov/pubmed/27597805

Cell type-specific tandem affinity purification of the mouse hippocampal CB1 receptor-associated proteome.

Posted on September 7, 2016 by David

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“G protein coupled receptors (GPCR’s) exert their effects through multiprotein signaling complexes. The cannabinoid receptor type 1 (CB1) is among the most abundant GPCR’s in the mammalian brain and involved in a plethora of physiological functions. We used a combination of viral-mediated cell type-specific expression of a tagged CB1 fusion protein (CB1-SF), tandem affinity purification (TAP) and proteomics on hippocampal mouse tissue to analyze the composition and differences of CB1 protein complexes in glutamatergic neurons and in GABAergic interneurons. Purified proteins underwent tryptic digestion and were identified using deep-coverage data-independent acquisition with ion mobility separation-enhanced mass spectroscopy, leading to the identification of 951 proteins specifically enriched in glutamatergic and GABAergic CB1-SF TAP samples as compared to controls. Gene Ontology and protein network analyses showed an enrichment of single proteins and functional clusters of proteins involved in already well described domains of CB1 functions. Supported by this consistent dataset we could confirm already known CB1 interactors, reveal new potentially interacting proteins and differences in cell type-specific signaling properties of CB1, thereby providing the foundation for further functional studies on differential CB1 signaling.”

http://www.ncbi.nlm.nih.gov/pubmed/27596989

Excess cerebral TNF causing glutamate excitotoxicity rationalizes treatment of neurodegenerative diseases and neurogenic pain by anti-TNF agents.

Posted on September 7, 2016 by David

“The basic mechanism of the major neurodegenerative diseases, including neurogenic pain, needs to be agreed upon before rational treatments can be determined, but this knowledge is still in a state of flux. Most have agreed for decades that these disease states, both infectious and non-infectious, share arguments incriminating excitotoxicity induced by excessive extracellular cerebral glutamate.

Excess cerebral levels of tumor necrosis factor (TNF) are also documented in the same group of disease states.

Here, we link the two, collecting and arguing the evidence that, across the range of neurodegenerative diseases, excessive TNF harms the central nervous system largely through causing extracellular glutamate to accumulate to levels high enough to inhibit synaptic activity or kill neurons and therefore their associated synapses as well.

TNF can be predicted from the broader literature to cause this glutamate accumulation not only by increasing glutamate production by enhancing glutaminase, but in addition simultaneously reducing glutamate clearance by inhibiting re-uptake proteins.

We also discuss the effects of a TNF receptor biological fusion protein (etanercept) and the indirect anti-TNF agents dithio-thalidomides, nilotinab, and cannabinoids on these neurological conditions. The therapeutic effects of 6-diazo-5-oxo-norleucine, ceptriaxone, and riluzole, agents unrelated to TNF but which either inhibit glutaminase or enhance re-uptake proteins, but do not do both, as would anti-TNF agents, are also discussed in this context.

By pointing to excess extracellular glutamate as the target, these arguments greatly strengthen the case, put now for many years, to test appropriately delivered ant-TNF agents to treat neurodegenerative diseases in randomly controlled trials.”

http://www.ncbi.nlm.nih.gov/pubmed/27596607

Protection against septic shock and suppression of tumor necrosis factor alpha and nitric oxide production by dexanabinol (HU-211), a nonpsychotropic cannabinoid.

Posted on September 7, 2016 by David

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“Dexanabinol, HU-211, a synthetic cannabinoid devoid of psychotropic effects, improves neurological outcome in models of brain trauma, ischemia and meningitis.

Recently, HU-211 was found to inhibit brain tumor necrosis factor (TNFalpha) production after head injury. In the present study, we demonstrate the ability of HU-211 to suppress TNFalpha production and to rescue mice and rats from endotoxic shock after LPS (Escherichia coli 055:B5) inoculation.

Administration of LPS to Sprague-Dawley rats resulted in a 30% reduction in the mean arterial blood pressure within 30 min, which persisted for 3 hr. HU-211, given 2 to 3 min before LPS, completely abolished the typical hypotensive response. Furthermore, the drug also markedly suppressed in vitro TNFalpha production and nitric oxide generation (by >90%) by both murine peritoneal macrophages and rat alveolar macrophage cell line exposed to LPS.

HU-211 may, therefore, have therapeutic implications in the treatment of TNFalpha-mediated pathologies.”

http://www.ncbi.nlm.nih.gov/pubmed/9353414