The effect of FAAH, MAGL, and Dual FAAH/MAGL inhibition on inflammatory and colorectal distension-induced visceral pain models in Rodents.

Posted on April 15, 2015 by David

“Recent studies showed that the pharmacological inhibition of endocannabinoid degrading enzymes such as fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) elicit promising analgesic effects in a variety of nociceptive models without serious side effects…

The selective FAAH inhibitor and dual FAAH/MAGL inhibitors were effective in both inflammatory and mechanically evoked visceral pain, while the MAGL inhibitor elicited an analgesic effect in inflammatory, but not in distension-induced, visceral pain.”

http://www.ncbi.nlm.nih.gov/pubmed/25869205

The Medicinal Chemistry of Cannabinoids.

Posted on March 25, 2015 by David

“The endocannabinoid system (ECS) comprises the two well characterized Gi/o -protein coupled receptors (CB1, CB2), their endogenous lipid ligands and the enzymes involved in their biosynthesis and biotransformation.

Drug discovery efforts relating to the ECS have been focused mainly on the two cannabinoid receptors and the two endocannabinoid deactivating enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MGL).

This review provides an overview of cannabinergic agents used in drug research and those being explored clinically.”

http://www.ncbi.nlm.nih.gov/pubmed/25801236

Spinal neuronal cannabinoid receptors mediate urodynamic effects of systemic fatty acid amide hydrolase (FAAH) inhibition in rats.

Posted on March 20, 2015 by David

“To test if urodynamic effects from systemic Fatty Acid Amide Hydrolase (FAAH) inhibition involve sacral spinal cannabinoid type 1 (CB1) or type 2 (CB2) receptors…

Urodynamic effects of systemic FAAH inhibition involve activities at spinal neuronal CB1 and CB2 receptors in normal and obstructed rats.

Endogenous spinal CB receptor ligands seem to regulate normal micturition and bladder overactivity (BO). Altered spinal CB receptor functions may be involved in the pathogenesis of obstruction-induced BO.”

http://www.ncbi.nlm.nih.gov/pubmed/25788026

Placental expression of the endocannabinoid system in preeclampsia.

Posted on March 20, 2015 by David

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/

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

Posted on March 4, 2015 by David

“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

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

Posted on February 27, 2015 by David

“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

Tapping into the endocannabinoid system to ameliorate acute inflammatory flares and associated pain in mouse knee joints.

Posted on September 28, 2014 by David

“During the progression of rheumatoid arthritis (RA), there are frequent but intermittent flares in which the joint becomes acutely inflamed and painful.

Although a number of drug therapies are currently used to treat RA, their effectiveness is variable and side effects are common.

Endocannabinoids have the potential to ameliorate joint pain and inflammation, but these beneficial effects are limited by their rapid degradation.

One enzyme responsible for endocannabinoid break down is fatty acid amide hydrolase (FAAH). The present study examined whether URB597, a potent and selective FAAH inhibitor, could alter inflammation and pain in a mouse model of acute synovitis.

Conclusions: These results suggest that the endocannabinoid system of the joint can be harnessed to decrease acute inflammatory reactions and the concomitant pain associated with these episodes.”

http://www.ncbi.nlm.nih.gov/pubmed/25260980

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

The endocannabinoid system as a potential therapeutic target for pain modulation.

Posted on September 11, 2014 by David

“Although cannabis has been used for pain management for millennia, very few approved cannabinoids are indicated for the treatment of pain and other medical symptoms.

Cannabinoid therapy re-gained attention only after the discovery of endocannabinoids and fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), the enzymes playing a role in endocannabinoid metabolism.

Nowadays, research has focused on the inhibition of these degradative enzymes and the elevation of endocannabinoid tonus locally; special emphasis is given on multi-target analgesia compounds, where one of the targets is the endocannabinoid degrading enzyme.

In this review, I provide an overview of the current understanding about the processes accounting for the biosynthesis, transport and metabolism of endocannabinoids, and pharmacological approaches and potential therapeutic applications in this area, regarding the use of drugs elevating endocannabinoid levels in pain conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/25207181

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

Targeting the Endocannabinoid System for Neuroprotection: A 19F-NMR Study of a Selective FAAH Inhibitor Binding with an Anandamide Carrier Protein, HSA.

Posted on February 24, 2014 by David

“Fatty acid amide hydrolase (FAAH), the enzyme involved in the inactivation of the endocannabinoid anandamide (AEA), is being considered as a therapeutic target for analgesia and neuroprotection…

The endocannabinoid system has been implicated as a therapeutic target for analgesia, anti-emesis, and neuroprotection… These findings provide a potential new therapeutic modality for neuroprotection through dual inhibition of FAAH and anandamide carrier proteins…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3921897/

5-Lipoxygenase and anandamide hydrolase (FAAH) mediate the antitumor activity of cannabidiol, a non-psychoactive cannabinoid.

Posted on January 26, 2014 by David

“It has been recently reported that cannabidiol (CBD), a non-psychoactive cannabinoid, is able to kill glioma cells, both in vivo and in vitro, independently of cannabinoid receptor stimulation.

…the present investigation indicates that CBD exerts its antitumoral effects through modulation of the LOX pathway and of the endocannabinoid system…”

http://www.ncbi.nlm.nih.gov/pubmed/18028339