Thursday, March 13, 2014

Cannabinoids: clearing the smoke on pain, inflammation and neurodegeneration

Ask your doctor what use this is for your stroke recovery.
http://onlinelibrary.wiley.com/doi/10.1111/bph.12642/full
This themed section of BJP arises from the 6th European Workshop on Cannabinoid Research held in Dublin, Ireland from 18–20 April 2013. The section brings together 3 reviews and 10 research articles, presenting a range of work across the cannabinoid field.
The review article by Fagan et al. (2014) addresses the impact of endogenous, plant-derived and synthetic cannabinoids on neuronal viability. This review summarizes common mechanisms of neurodegeneration (including mitochondrial dysfunction, neuroinflammation and excitotoxicity) in three prominent age-related neurodegenerative disorders, Alzheimers' disease, Parkinson's disease and Huntington's disease. The review focuses on literature highlighting the cannabinoid system as a bona fide therapeutic target against such neurodegenerative processes. In addition, this review brings us up-to-date on the close links between the endocannabinoid system, ageing and the process of adult neurogenesis.
Stanley and O'Sullivan (2014) review the vascular targets of cannabinoids. They examine the evidence for the range of receptors activated by cannabinoids in perfused vascular beds or isolated arteries. Direct targets of synthetic, plant-derived or endogenous cannabinoids include CB1, CBe, TRPV1, peroxisome proliferator-activated receptors (PPARs), CB2, GPR55 and 5-HT1A receptors. Prostanoid receptors and the calcitonin gene-related peptide (CGRP) receptor can also indirectly mediate the vascular response to cannabinoids. Typically cannabinoids have vasorelaxant effects, although vasoconstriction has also been observed in some instances. Animal and human studies are reviewed.
The third review article discusses one of the most abundant endocannabinoids, 2-arachidonylglycerol (2-AG), and summarizes the latest major discoveries associated with the complex pathways leading to 2-AG synthesis and metabolism in the central nervous system (CNS) (Murataeva et al., 2014). This review addresses the spatial and temporal expression of diacylglycerol lipases (DAGL) in the CNS, the most heavily studied pathway for 2-AG synthesis. Intriguing questions regarding 2-AG metabolizing enzymes are considered, including their activity in different cellular compartments and their contribution to endogenous 2-AG-based signalling. The review highlights that the various enzymes for synthesizing and degrading 2-AG represent potential therapeutic targets for neurodegenerative and inflammatory diseases.
Research on the function of 2-AG has been facilitated in recent years by the availability of some selective and potent inhibitors of the catabolising enzyme monoacylglycerol lipase (MAGL). One such inhibitor is the compound KML29 and Ignatowska-Jankowska et al. (2014) present novel data herein on the effects of this MAGL inhibitor in mouse models of inflammatory (carrageenan) and neuropathic (sciatic nerve injury) pain. Their results show that systemic administration of KML29 attenuates carrageenan-induced paw oedema and reverses carrageenan-induced mechanical allodynia. Tolerance to these effects of KML29 and CB1 receptor desensitization developed after repeated administration of high doses. Moreover, KML29 partially reversed sciatic nerve injury-induced allodynia and prevented diclofenac-induced gastric haemorrhages, without eliciting cannabimimetic effects in the tetrad test. These preclinical data suggest that MAGL inhibitors show promise as novel analgesics with a favourable side-effect profile.

More at link.


No comments:

Post a Comment