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

“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.

“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.

“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.

“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

Emerging targets and therapeutic approaches for the treatment of osteoarthritis pain.

“Osteoarthritis is a complex and often painful disease that is inadequately controlled with current analgesics. This review discusses emerging targets and therapeutic approaches that may lead to the development of better analgesics…

Aberrant excitability in peripheral and central pain pathways drives osteoarthritis pain, reversing this via modulation of nerve growth factor, voltage-gated sodium channel, voltage-gated calcium channel and transient receptor potential vanilloid one activity, and increasing inhibitory mechanisms through modulation of cannabinoid and descending modulatory systems hold promise for osteoarthritis pain therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/25730180

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

 

Peripheral cannabinoid receptor, CB2, regulates bone mass.

“Here we show that CB2-deficient mice have a markedly accelerated age-related trabecular bone loss and cortical expansion, although cortical thickness remains unaltered.

These changes are reminiscent of human osteoporosis and may result from differential regulation of trabecular and cortical bone remodeling…

These results demonstrate that the endocannabinoid system is essential for the maintenance of normal bone mass by osteoblastic and osteoclastic CB2 signaling.

Hence, CB2 offers a molecular target for the diagnosis and treatment of osteoporosis, the most prevalent degenerative disease in developed countries.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1334629/

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

 

Marijuana: A Time-Honored but Untested Treatment for Epilepsy.

Image result for marijuana

“The biology of the endocannabinoid system in the brain provides a possible basis for a beneficial pharmacological effect of marijuana on seizures.

However, evidence for efficacy of cannabis treatment of epilepsy is anecdotal because no acceptable randomized controlled trials have been done.

Proper dosage and means of administration remain unknown.

Cannabis is safer than other controlled substances, including tobacco or alcohol, and appears to be relatively safe compared with most pharmaceuticals used to treat epilepsy.”

 http://www.ncbi.nlm.nih.gov/pubmed/25715711

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

Simultaneous inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) shares discriminative stimulus effects with ∆9-THC in mice.

“Δ9 -tetrahydrocannabinol (∆9 -THC) is a cannabinoid CB1 /CB2 receptor agonist that produces therapeutic effects such as analgesia and anti-emetic effects…

Collectively, the current results show that pharmacological increases in endogenous AEA and 2-AG simultaneously through inhibition of FAAH and MAGL, respectively, mimics the discriminative stimulus effects of Δ9 -THC.”

http://jpet.aspetjournals.org/content/early/2015/02/24/jpet.115.222836.long

Influence of nitric oxide synthase or cyclooxygenase inhibitors on cannabinoids activity in streptozotocin-induced neuropathy.

“The results of this study seemed to indicate that the interaction between cannabinoid, COX-2 and NOS(s) systems might exist…

Concomitant administration of small doses of CB1 and/or CB2 receptor agonists and COX-2 or NOS inhibitors can be effective in the alleviation of diabetic neuropathic pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25712641

http://www.thctotalhealthcare.com/category/neuropathic-pain/

The role of cannabinoids in regulation of nausea and vomiting, and visceral pain.

“Marijuana derived from the plant Cannabis sativa has been used for the treatment of many gastrointestinal (GI) disorders, including anorexia, emesis, abdominal pain, diarrhea, and others.

Several cannabinoid receptors, which include the cannabinoid receptor 1 (CB1), CB2, and possibly GPR55, have been identified throughout the GI tract.

These receptors may play a role in the regulation of food intake, nausea and emesis, gastric secretion and gastroprotection, GI motility, ion transport, visceral sensation, intestinal inflammation, and cell proliferation in the gut.

…the regulation of nausea and vomiting by cannabinoids and the endocannabinoid system has shed new knowledge in this field.

Novel drug targets such as FAAH and monoacylglycerol lipase (MAGL) inhibitors appear to be promising in animal models, but more studies are necessary to prove their efficiency.

The promise of emerging drugs that are more selective and peripherally acting suggest that, in the near future, cannabinoids will play a major role in managing an array of GI diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/25715910