Effect of dietary fat on endocannabinoids and related mediators: Consequences on energy homeostasis,inflammation and mood

Among the several known fatty acid‐derived chemical signals, the endogenous ligands of cannabinoid receptors type‐1 and ‐2, two G‐protein‐coupled receptors involved in several aspects of mammalian physiology and pathology, are perhaps those the levels of which have proven to be most sensitive to the fatty acid composition of the diet. The two most studied such ligands, known as endocannabinoids, are N‐arachidonoyl‐ethanolamine and 2‐archidonoylglycerol, and are found in tissues together with other N‐acyl‐ethanolamines and 2‐acylglycerols, not all of which activate the cannabinoid receptors, although several of them do exhibit important pharmacological effects. In this review article, we describe literature data indicating that the tissue concentrations of the endocannabinoids and related signalling molecules, and hence the activity of the respective receptors, can be modulated by modifying the fatty acid composition of the diet, and particularly its content in long chain PUFAs or in long chain PUFA precursors. We also discuss the potential impact of these diet‐induced changes of endocannabinoid tone on three of the major pathological conditions in which cannabinoid receptors have been involved, that is metabolic dysfunctions, inflammation and affective disorders.     

Lipocalin‐Type Prostaglandin D Synthase Is a Novel Phytocannabinoid‐Binding Protein

Lipocalin‐type prostaglandin D synthase (L‐PGDS; EC:5.3.99.2) is an enzyme with dual functional roles as a prostaglandin D₂‐synthesizing enzyme and as an extracellular transporter for diverse lipophilic compounds in the cerebrospinal fluid (CSF). Transport of hydrophobic endocannabinoids is mediated by serum albumin in the blood and intracellularly by the fatty acid binding proteins, but no analogous transport mechanism has yet been described in CSF. L‐PGDS has been reported to promiscuously bind a wide variety of lipophilic ligands and is among the most abundant proteins found in the CSF. Here, we examine the binding of several classes of endogenous and synthetic ligands to L‐PGDS. Endocannabinoids exhibited low affinity toward L‐PGDS, while cannabinoid metabolites and synthetic cannabinoids displayed higher affinities for L‐PGDS. These results indicate that L‐PGDS is unlikely to function as a carrier for endocannabinoids in the CSF, but it may bind and transport a subset of cannabinoids.     

Novel Method for Synthesis of Diarylpyrazole Derivatives as Cannabinoid CB1 Receptor Antagonists

A novel and efficient method was developed for the synthesis of diarylpyrazole derivatives as cannabinoid CB1 receptor antagonist via four step reactions.The key step was the synthesis of a diarylpyrazole skeleton,which involved initial condensation of the sodium salt of compound 12 with diazonium compounds,and further cyclization by heating at reflux in acetic acid.Eight diarylpyrazole derivatives and nine new synthesized compounds were cha racterized by 1H NMR,IR,MS,and elemental analysis.The reaction conditions were mild and the overall yields of the target compounds ranged from 26% to 44%.     

Mooreamide A: A Cannabinomimetic Lipid from the Marine Cyanobacterium Moorea bouillonii

Bioassay‐guided fractionation of a collection of Moorea bouillonii from Papua New Guinea led to the isolation of a new alkyl amide, mooreamide A ( 1 ), along with the cytotoxic apratoxins A–C and E. The planar structure of 1 was elucidated by NMR spectroscopy and mass spectrometry analysis. Structural homology between mooreamide A and the endogenous cannabinoid ligands, anandamide, and 2‐arachidonoyl glycerol inspired its evaluation against the neuroreceptors CB₁ and CB₂. Mooreamide A was found to possess relatively potent and selective ligand binding activity to CB₁ (K₁ = 0.47 µM) versus CB₂ (K₁ > 25 µM). This represents the most potent marine‐derived CB₁ ligand described to date and adds to the growing family of marine metabolites that exhibit cannabinomimetic activity.     

Development and validation of LC-MS/MS method with QuEChERS clean-up for detecting cannabinoids in foods and dietary supplements

ABSTRACT

a rapid and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of cannabidiol (CBD) and Δ⁹-tetrahydrocannabinol (THC) using a QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) clean-up for a variety of foods and dietary supplements (DS). QuEChERS is widely used in extraction or clean-up procedures to eliminate interference of matrices such as sugars, organic acids, lipids, and fatty acids. The samples were categorised into three types, and various pretreatment methods were compared for each type. In all types, the QuEChERS was superior and selected as the final pretreatment method. The optimised method was validated for specificity, limit of detection (LOD), limit of quantification (LOQ), linearity, recovery, precision and accuracy. All of the validation results met the requirements of the international guidelines for all types of samples. The validated method was applied to 30 commercial food samples, CBD was detected in 17 samples, with 2 of them detected below the LOQ level and the rest detected in a range of 70 μg/kg to 31305 mg/kg (3.1%, w/w). Meanwhile, THC was detected in 14 samples; 2 of them were detected below the LOQ level and the rest detected in a 0.08–98.62 μg/g range. These results indicated that the validated method can be successfully applied for the determination of cannabinoids in a variety of samples. Furthermore, it will be useful for controlling the illegal distribution of cannabinoids.