“Neuropathic pain is a neurological disorder that strongly affects the quality of life of patients. The molecular and cellular mechanisms at the basis of the neuropathic pain establishment still need to be clarified. Among the neuromodulators involved in the pathological pain pathways, endocannabinoid system could be deeply involved in both neuronal and non-neuronal mechanisms responsible for the appearance of tactile allodynia. Indeed, the function and dysfunction of this complex system in the molecular and cellular mechanisms of chronic pain induction and maintenance has been widely studied over the last two decades. In this review article, we highlighted the possible modulation of the endocannabinoid system in the neuronal, glial and microglial modulation in neuropathic pain treatment.” https://www.ncbi.nlm.nih.gov/pubmed/28237514]]>
Category Archives: Endocannabinoid System
Chronic and acute adenosine A2A receptor blockade prevents long-term episodic memory disruption caused by acute cannabinoid CB1 receptor activation.
“Cannabinoid-mediated memory impairment is a concern in cannabinoid-based therapies. Caffeine exacerbates cannabinoid CB1receptor (CB1R)-induced memory deficits through an adenosine A1 receptor-mediated mechanism. We now evaluated how chronic or acute blockade of adenosine A2A receptors (A2ARs) affects long-term episodic memory deficits induced by a single injection of a selective CB1R agonist. The finding that CB1R-mediated memory disruption is prevented by antagonism of adenosine A2ARs, highlights a possibility to prevent cognitive side effects when therapeutic application of CB1R drugs is desired.” https://www.ncbi.nlm.nih.gov/pubmed/28235548]]>
FAAH inhibition produces antidepressant-like efforts of mice to acute stress via synaptic long-term depression.
“Recent studies have shown that inhibition of fatty acid amide hydrolase (FAAH), the major degradative enzyme of the endocannabinoid N-arachidonoylethanolamine (AEA), produced antidepressant behavioral responses, but its underlying mechanism is not clear. Here we find that a systemic administration of the FAAH inhibitor PF3845 or an intra-CA1 application of AEA elicits an in vivo long-term depression (LTD) at excitatory glutamatergic CA3-CA1 synapses of the hippocampus. The PF3845- and/or AEA-elicited LTD are abolished by the LTD-blocking peptide Tat-GluR2. PF3845 significantly decreases passive behavioral coping of naïve mice to acute inescapable stress, which is also abolished by Tat-GluR2 peptide. However, PF3845 does not significantly affect sucrose assumption ratio of mice receiving chronic administration of corticosterone. These results suggest that FAAH inhibitors are able to produce antidepressant effects in naïve animals in response to acute stress through LTD at hippocampal glutamatergic CA3-CA1 synapses.” https://www.ncbi.nlm.nih.gov/pubmed/28193523]]>
Fatty acid amide hydrolase inhibitors produce rapid anti-anxiety responses through amygdala long-term depression in male rodents.
CONCLUSION:
We propose that the rapid anti-anxiety effects of FAAH inhibition are due to AEA activation of astroglial CB1R and subsequent basolateral amygdala LTD in vivo.” https://www.ncbi.nlm.nih.gov/pubmed/28234213Leaner and greener analysis of cannabinoids
“There is an explosion in the number of labs analyzing cannabinoids in marijuana (Cannabis sativa L., Cannabaceae) but existing methods are inefficient, require expert analysts, and use large volumes of potentially environmentally damaging solvents. The objective of this work was to develop and validate an accurate method for analyzing cannabinoids in cannabis raw materials and finished products that is more efficient and uses fewer toxic solvents. An HPLC-DAD method was developed for eight cannabinoids in cannabis flowers and oils using a statistically guided optimization plan based on the principles of green chemistry. A single-laboratory validation determined the linearity, selectivity, accuracy, repeatability, intermediate precision, limit of detection, and limit of quantitation of the method. Amounts of individual cannabinoids above the limit of quantitation in the flowers ranged from 0.02 to 14.9% w/w, with repeatability ranging from 0.78 to 10.08% relative standard deviation. The intermediate precision determined using HorRat ratios ranged from 0.3 to 2.0. The LOQs for individual cannabinoids in flowers ranged from 0.02 to 0.17% w/w. We developed an optimized HPLC-DAD method with reduced extraction time and greener solvents for adoption into cannabis testing laboratories. Sample turnaround is significantly reduced, while method validation confirmed that the method produces repeatable, accurate results. The sample preparation eliminates the use of chloroform, which has been routinely used in cannabinoid analysis, reducing material costs, use of greener solvents, and improved laboratory safety for personnel. This method can be used in a variety of settings from clinical studies, research, quality control, and regulatory evaluation of this growing industry. This is a significant improvement over previous methods and is suitable for a wide range of applications including regulatory compliance, clinical studies, direct patient medical services, and commercial suppliers.” https://link.springer.com/article/10.1007/s00216-017-0256-3]]>
Cannabidiol: State of the art and new challenges for therapeutic applications.
“Over the past years, several lines of evidence support a therapeutic potential of Cannabis derivatives and in particular phytocannabinoids. Δ9-THC and cannabidiol (CBD) are the most abundant phytocannabinoids in Cannabis plants and therapeutic application for both compounds have been suggested. However, CBD is recently emerging as a therapeutic agent in numerous pathological conditions since devoid of the psychoactive side effects exhibited instead by Δ9-THC. In this review, we highlight the pharmacological activities of CBD, its cannabinoid receptor-dependent and -independent action, its biological effects focusing on immunomodulation, angiogenetic properties, and modulation of neuronal and cardiovascular function. Furthermore, the therapeutic potential of cannabidiol is also highlighted, in particular in nuerological diseases and cancer.” https://www.ncbi.nlm.nih.gov/pubmed/28232276]]>
The cannabinoid 1 receptor antagonist, AM251, prolongs the survival of rats with severe acute pancreatitis.
“It has recently been recognized that anandamide (arachidonylethanolamide), which is an endogeneous-cannabinoid (endocannabinoid), mediates septic shock.
Cannabinoid means a mind-active material in cannabis (marijuana).
Anandamide is mainly produced by macrophages. Cannabinoid 1 (CB1) receptor, which is one of the cannabiniod receptors, is also known to mediate hypotensive shock.
The role of endocannabinoids in the progression of acute pancreatitis is unclear. The aims of this study are to clarify their relationship and to find a new therapeutic strategy by regulating the endocannabinoid signaling in acute pancreatitis.
This is the first report to show that endocannabinoids are involved in the deterioration of acute pancreatitis and that the down-regulation of endocannabinoid signaling may be a new therapeutic strategy for severe acute pancreatitis.”
“Obesity is a risk factor for increased severity of acute 