The relationship of endocannabinoidome lipid mediators with pain and psychological stress in women with fibromyalgia – a case control study.

“Characterized by chronic widespread pain, generalized hyperalgesia, and psychological stress fibromyalgia (FM) is difficult to diagnose and lacks effective treatments.

The endocannabinoids – arachidonoylethanolamide (AEA), 2-arachidonoylglycerol (2-AG), and the related oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) – are endogenous lipid mediators with analgesic and anti-inflammatory characteristics, in company with psychological modulating properties (e.g., stress and anxiety), and are included in a new emerging “ome”, the endocannabinoidome.

This case -control study compared the concentration differences of AEA, OEA, PEA, SEA, and 2-AG in 104 women with FM and 116 healthy controls (CON). All participants OEArated their pain, anxiety, depression, and current health status. The relationships between the lipid concentrations and the clinical assessments were investigated using powerful multivariate data analysis and traditional bivariate statistics. The concentrations of OEA, PEA, SEA, and 2-AG were significantly higher in FM than in CON; significance remained for OEA and SEA after controlling for BMI and age. 2-AG correlated positively with FM duration and BMI, and to some extent negatively with pain, anxiety, depression, and health status. In FM, AEA correlated positively with depression ratings.

The elevated circulating levels of endocannabinoidome lipids suggest that these lipids play a role in the complex pathophysiology of FM and might be signs of ongoing low-grade inflammation in FM. Although the investigated lipids are significantly altered in FM their biological roles are uncertain with respect to the clinical manifestations of FM. Thus, plasma lipids alone are not good biomarkers for FM.

PERSPECTIVE:

This study reports about elevated plasma levels of endocannabinoidome lipid mediators in FM. The lipids suitability to work as biomarkers for FM in the clinic were low, however their altered levels indicate that a metabolic asymmetry is ongoing in FM, which could serve as basis during explorative FM pain management.”

https://www.ncbi.nlm.nih.gov/pubmed/29885369

https://www.jpain.org/article/S1526-5900(18)30197-4/fulltext

Oleoylethanolamine and palmitoylethanolamine modulate intestinal permeability in vitro via TRPV1 and PPARα.

Image result for FASEB J.

“Cannabinoids modulate intestinal permeability through CB1.

The endocannabinoid-like compounds oleoylethanolamine (OEA) and palmitoylethanolamine (PEA) play an important role in digestive regulation, and we hypothesized they would also modulate intestinal permeability.

OEA and PEA have endogenous roles and potential therapeutic applications in conditions of intestinal hyperpermeability and inflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/27623929

Circulating endocannabinoids and N-acyl-ethanolamides in patients with sleep apnea–specific role of oleoylethanolamide.

“OBJECTIVE:  The endocannabinoid system promotes diverse effects on fat and glucose metabolism as well as on energy balance and sleep regulation. The role of N-acylethanolamides like oleoylethanolamide (OEA) and other endocannabinoids such as anandamide (AEA) and 2-arachidonyl-glycerol (2-AG) has not yet been investigated in patients with sleep apnea.

 

CONCLUSIONS: These results indicate that among the three analyzed fatty acid derivatives, OEA plays a specific role in patients with sleep apnea. Together with animal data, the 2-fold elevation of OEA serum concentrations could be interpreted as a neuroprotective mechanism against chronic oxidative stressors and a mechanism to promote wakefulness in patients with nocturnal sleep deprivation and daytime hypersomnolence.”

http://www.ncbi.nlm.nih.gov/pubmed/20429051

 

Endocannabinoids Measurement in Human Saliva as Potential Biomarker of Obesity

Background

“The discovery of the endocannabinoid system and of its role in the regulation of energy balance has significantly advanced our understanding of the physiopathological mechanisms leading to obesity and type 2 diabetes. New knowledge on the role of this system in humans has been acquired by measuring blood endocannabinoids. Here we explored endocannabinoids and related N-acylethanolamines in saliva and verified their changes in relation to body weight status and in response to a meal or to body weight loss.”

“The discovery of the endocannabinoid system (ECS) and of its impact on the regulation of energy homeostasis represents a significant advance in the study of obesity and type 2 diabetes [1][4].”

“The saliva is the first digestive secretion produced in response to the ingestion of food [11]. Therefore, it is reasonable to investigate whether signals and systems involved in the regulation of food intake, such as the ECS, might be present in saliva and exert a functional role. Besides, saliva offers distinctive advantages over serum or plasma as a diagnostic tool, thanks to the non-invasiveness of the collection procedure.”

“The ECS is present in human salivary glands.”

“Changes in salivary endocannabinoids and N-acylethanolamines levels in response to body weight loss.”

“Here we demonstrate that endocannabinoids and related N-acylethanolamines can be reliably detected and quantified in human saliva. Similarly to what already reported for circulating levels in the blood [7], [9], [10], the salivary concentration of AEA and OEA were significantly increased in obese, insulin-resistant subjects as compared to normal weight controls.”

“the present findings overall indicate that salivary AEA might be a useful biomarker in human obesity, in particular considering that salivary samples are easy to collect, require a non-invasive procedure advantageous when performing studies in obese subjects in whom venipuncture may be difficult, and can be repeatedly collected at home by the patient during a therapeutic intervention. This type of tool could therefore be used to better phenotype the obese population, assess responses to treatment, or to further study the physiology of the ECS in humans, by investigating salivary endocannabinoid responses under various conditions.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3409167/