Tag Archives: endocannabinoid system

For whom the endocannabinoid tolls: Modulation of innate immune function and implications for psychiatric disorders.

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“Over the past decade, there has been increasing evidence demonstrating that the endocannabinoid system can elicit potent modulatory effects on inflammatory processes, with clinical and preclinical evidence demonstrating beneficial effects on disease severity and symptoms in several inflammatory conditions.

This review examines the evidence supporting a modulatory effect of endocannabinoids on TLR-mediated immune responses both peripherally and centrally, and the implications for psychiatric disorders such as depression and schizophrenia.

CLASSES OF CANNABINOID-BASED PHARMACOLOGICAL AGENTS CITED IN THE REVIEW: Nonselective CB1/CB2 agonists: Δ9-THC, HU210, CP55940, WIN55,212-2 Selective CB2 agonists: JWH-015 FAAH inhibitors: URB597, AA-5HT MAGL/ABHD6 inhibitors: JZL184, MJN110, KML129, WWL70 Endocannabinoid reuptake inhibitors: UCM707, OMDM1/2, AM404.”

http://www.ncbi.nlm.nih.gov/pubmed/25794989

The endocannabinoid system and its therapeutic implications in rheumatoid arthritis.

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“Since the discovery of the endogenous receptor for Δ9-tetrahydrocannabinol, a main constituent of marijuana, the endocannabinoid system (comprising cannabinoid receptors and their endogenous ligands, as well as the enzymes involved in their metabolic processes) has been implicated as having multiple regulatory functions in many central and peripheral conditions, including rheumatoid arthritis (RA).

RA is an immune-mediated inflammatory disease that is associated with the involvement of many kinds of cells (such as fibroblastlike synoviocytes [FLSs], osteoclasts, T cells, B cells, and macrophages) and molecules (such as interleukin-1β, tumor necrosis factor-α, interleukin-6, matrix metalloproteinases [MMPs], and chemokines). Increasing evidence suggests that the endocannabinoid system, especially cannabinoid receptor 2 (CB2), has an important role in the pathophysiology of RA.

Many members of the endocannabinoid system are reported to inhibit synovial inflammation, hyperplasia, and cartilage destruction in RA.

In particular, specific activation of CB2 may relieve RA by inhibiting not only the production of autoantibodies, proinflammatory cytokines, and MMPs, but also bone erosion, immune response mediated by T cells, and the proliferation of FLSs.

In this review, we will discuss the possible functions of the endocannabinoid system in the modulation of RA, which may be a potential target for treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/25791728

http://www.thctotalhealthcare.com/category/rheumatoid-arthritis-2/

 

The potential of inhibitors of endocannabinoid metabolism as anxiolytic and antidepressive drugs-A practical view.

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“The endocannabinoid system, comprising cannabinoid CB1 and CB2 receptors, their endogenous ligands anandamide and 2-arachidonoylglyerol, and their synthetic and metabolic enzymes, are involved in many biological processes in the body, ranging from appetite to bone turnover.

Compounds inhibiting the breakdown of anandamide and 2-arachidonoylglycerol increase brain levels of these lipids and thus modulate endocannabinoid signalling.

In the present review, the preclinical evidence that these enzymes are good targets for development of novel therapies for anxiety and depression are discussed from a practical, rather than mechanistic, point of view.

It is concluded that the preclinical data are promising, albeit tempered by problems of tolerance as well as effects upon learning and memory for irreversible monoacylglycerol lipase inhibitors, and limited by a focus upon male rodents alone.

Clinical data so far has been restricted to safety studies with inhibitors of anandamide hydrolysis and a hitherto unpublished study on such a compound in elderly patients with major depressive disorders, but under the dose regimes used, they are well tolerated and show no signs of “cannabis-like” behaviours.”

http://www.ncbi.nlm.nih.gov/pubmed/25791296

Placental expression of the endocannabinoid system in preeclampsia.

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Pregnancy Hypertension: An International Journal of Women's Cardiovascular Health

“In the present study, we aimed to analyze cannabinoid receptor 1 (CB1), CB2 and fatty acid amid hydrolase (FAAH) expressions and localization in normal and preeclamptic placenta, in order to determine whether aberrant endocannabinoid activity is related to preeclampsia…

We observed markedly higher expression of CB1 protein in preeclamptic placental tissue. Increased CB1 expression might cause abnormal decidualization and impair trophoblast invasion, thus being involved in the pathogenesis of preeclampsia. As CB1 activation can induce endothelial dysfunction and enhance vascular inflammation, the strong CB1 immunoreaction in vascular endothelial and smooth muscle cells suggests that CB1 may contribute to the development of atherosis in the placental villi shown earlier in preeclampsia.

While the detailed pathogenesis of preeclampsia is still unclear, the endocannabinoid system could play a role in the development of the disease.”

http://www.ncbi.nlm.nih.gov/pubmed/25787618

https://www.sciencedirect.com/science/article/pii/S2210778914003754

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

Attenuation of kainic acid-induced status epilepticus by inhibition of endocannabinoid transport and degradation in guinea pigs.

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“Status epilepticus (SE) is a medical emergency associated with a high rate of mortality if not treated promptly.

Exogenous and endogenous cannabinoids have been shown to possess anticonvulsant properties both in vivo and in vitro.

Here we study the influence of endocannabinoid metabolism on the development of kainic acid-induced SE in guinea pigs.

The present study provides electrophysiologic and behavioral evidences that inhibition of endocannabinoid metabolism plays a protective role against kainic acid-induced SE and may be employed for therapeutic purposes.”

http://www.ncbi.nlm.nih.gov/pubmed/25769371

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

Role of endogenous cannabinoid system in the gut.

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“The plant Cannabis has been used in clinic for centuries, and has been known to be beneficial in a variety of gastrointestinal diseases, such as emesis, diarrhea, inflammatory bowel disease and intestinal pain.

In this text, we’ll review the components of the endogenous cannabinoid system as well as its role in the regulation of gastrointestinal activities, thus providing relative information for further study.

Moreover, modulation of the endogenous cannabinoid system in gastrointestinal tract may provide a useful therapeutic target for gastrointestinal disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/23963077

http://www.thctotalhealthcare.com/category/gastrointestinal-disorders/

Identification of the CB1 cannabinoid receptor and fatty acid amide hydrolase (FAAH) in the human placenta.

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“Synthetic cannabinoids, the psychoactive components of the Cannabis sativa (marijuana) and their endogenous counterparts, act through two G protein-coupled receptors, CB1 and CB2.

The endocannabinoids are metabolized by fatty acid amide hydrolase (FAAH).

We have examined CB1 receptor and FAAH expression in human term placenta by immunohistochemistry.

CB1 receptor was found to be present in all layers of the membrane, with particularly strong expression in the amniotic epithelium and reticular cells and cells of the maternal decidua layer. Moderate expression was observed in the chorionic cytotrophoblasts. The expression of FAAH was the highest in amniotic epithelial cells, chorionic cytotrophoblast and maternal decidua layer.

Our results suggest that the human placenta is a likely target for cannabinoid action and metabolism. ”

http://www.ncbi.nlm.nih.gov/pubmed/12744923

A common variation in the cannabinoid 1 receptor (CNR1) gene is associated with pre-eclampsia in the Central European population.

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“Recently it has been proposed that tightly regulated levels of endogenous cannabinoids play a fundamental role in early placental development.

The aim of this study was to investigate associations of three single-nucleotide polymorphisms (SNPs) in the cannabinoid 1 receptor (CNR1) gene (rs1049353, rs12720071 and rs806368) and their inferred haplotypes with pre-eclampsia, a severe pregnancy-associated condition characterized by abnormal development and remodeling of spiral decidual arteries…

This is the first study focusing on the relationship between SNPs in the CNR1 gene and pre-eclampsia risk.

Although limited by a relatively small sample size, the study indicates that rs806368 in the CNR1 gene may act as a susceptibility marker for pre-eclampsia in humans.”

http://www.ncbi.nlm.nih.gov/pubmed/21129839

Differential expression of endocannabinoid system in normal and preeclamptic placentas: effects on nitric oxide synthesis.

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“Anandamide (AEA) is a lipid mediator that participates in the regulation of several reproductive functions.

This study investigated the endocannabinoid system in normal (NP) and preeclamptic (PE) placentas, and analyzed the potential functional role of AEA in the regulation of nitric oxide synthesis…

These data suggest that AEA may be one of the factors involved in the regulation of NOS activity in normal and preeclamptic placental villous.

Interestingly, the differential expression of NAPE-PLD and FAAH suggests that AEA could play an important role in the pathophysiology of PE.”

http://www.ncbi.nlm.nih.gov/pubmed/23122699

Decreased circulating anandamide levels in preeclampsia.

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“The endocannabinoid system has a key role in female reproduction, including implantation, decidualization and placentation. A growing number of studies indicate that placental and peripheral blood anandamide levels correlate closely with both spontaneous miscarriage and ectopic pregnancy.

Anandamide has also been implicated in blood pressure regulation.

In this study, we aimed to determine circulating anandamide levels in preeclampsia for the first time in the literature…

In conclusion, we demonstrated for the first time in the literature that serum anandamide concentrations are decreased in women with preeclampsia.”

http://www.ncbi.nlm.nih.gov/pubmed/25716652