The Endocannabinoid system : a look back and ahead

Over the last few decades research on the cannabinoids has gone through several distinct phases: A. Research on plant cannabinoids (mostly on tetrahydrocannabinol (THC) and cannabidiol (CBD)) B. Research on endogenous cannabinoids (mostly on anandamide and 2-arachidonoyl glycerol (2-AG)) C. Research on endogenous anandamide-like endogenous fatty acid amides with amino acids and ethanol amines.peer-reviewe

CBD

A comprehensive review of the scientific literature on the possible benefits of CBD, describing findings from both preclinical and human clinical studies. CBD (cannabidiol), a nonintoxicating compound derived from the cannabis plant, can be found in products ranging from lotion and smoothies to chewable gummies and pet treats. It's been promoted—but not always scientifically validated—as a treatment for medical conditions including psychosis, anxiety, pain, and even cancer. In this book, three leading cannabis researchers look at the science of CBD, offering a comprehensive review of the scientific literature on the possible benefits of CBD and describing their findings from both preclinical and human clinical studies. As it turns out, the current CBD fad has some basis in preclinical animal research that indicates potential beneficial effects. Clinical studies, hampered by regulations governing research with cannabis, have lagged behind the basic animal research. The authors examine what research shows about chemical and pharmacological aspects of CBD and CBD's interaction with THC, the main psychotropic compound found in cannabis. They go on to review the current state of knowledge about CBD's effectiveness in treating epilepsy, cancer, nausea, pain, anxiety, PTSD, depression, sleep disorders, psychosis, and addiction

Prospects for Creation of Cardioprotective Drugs Based on Cannabinoid Receptor Agonists

Cannabinoids can mimic the infarct-reducing effect of early ischemic preconditioning, delayed ischemic preconditioning, and ischemic postconditioning against myocardial ischemia/reperfusion. They do this primarily through both CB1 and CB2 receptors. Cannabinoids are also involved in remote preconditioning of the heart. The cannabinoid receptor ligands also exhibit an antiapoptotic effect during ischemia/reperfusion of the heart. The acute cardioprotective effect of cannabinoids is mediated by activation of protein kinase C, extracellular signal-regulated kinase, and p38 kinase. The delayed cardioprotective effect of cannabinoid anandamide is mediated via stimulation of phosphatidylinositol-3-kinase-Akt signaling pathway and enhancement of heat shock protein 72 expression. The delayed cardioprotective effect of another cannabinoid, Δ9-tetrahydrocannabinol, is associated with augmentation of nitric oxide (NO) synthase expression, but data on the involvement of NO synthase in the acute cardioprotective effect of cannabinoids are contradictory. The adenosine triphosphate-sensitive K+ channel is involved in the synthetic cannabinoid HU-210-induced cardiac resistance to ischemia/reperfusion injury. Cannabinoids inhibit Na+/Ca2+ exchange via peripheral cannabinoid receptor (CB2) activation that may also be related to the antiapoptotic and cardioprotective effects of cannabinoids. The cannabinoid receptor agonists should be considered as prospective group of compounds for creation of drugs that are able to protect the heart against ischemia–reperfusion injury in the clinical setting. </jats:p

Cannabinoid receptors in GtoPdb v.2023.1

Cannabinoid receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Cannabinoid Receptors [119]) are activated by endogenous ligands that include N-arachidonoylethanolamine (anandamide), N-homo-&#947;-linolenoylethanolamine, N-docosatetra-7,10,13,16-enoylethanolamine and 2-arachidonoylglycerol. Potency determinations of endogenous agonists at these receptors are complicated by the possibility of differential susceptibility of endogenous ligands to enzymatic conversion [5].There are currently three licenced cannabinoid medicines each of which contains a compound that can activate CB1 and CB2 receptors [111]. Two of these medicines were developed to suppress nausea and vomiting produced by chemotherapy. These are nabilone (Cesamet&#174;), a synthetic CB1/CB2 receptor agonist, and synthetic &#916;9-tetrahydrocannabinol (Marinol&#174;; dronabinol), which can also be used as an appetite stimulant. The third medicine, Sativex&#174;, contains mainly &#916;9-tetrahydrocannabinol and cannabidiol, both extracted from cannabis, and is used to treat multiple sclerosis and cancer pain

Endocannabinoid basis of personality—Insights from animal model of social behavior

Rationale: The endocannabinoid system is known to be involved in learning, memory, emotional processing and regulation of personality patterns. Here we assessed the endocannabinoid profile in the brains of mice with strong characteristics of social dominance and submissiveness.Methods: A lipidomics approach was employed to assess the endocannabinoidome in the brains of Dominant (Dom) and Submissive (Sub) mice. The endocannabinoid showing the greatest difference in concentration in the brain between the groups, docosatetraenoyl ethanolamine (DEA), was synthesized, and its effects on the physiological and behavioral responses of Dom and Sub mice were evaluated. mRNA expression of the endocannabinoid receptors and enzymes involved in PUFA biosynthesis was assessed using qRT-PCR.Results: Targeted LC/MS analysis revealed that long-chain polyunsaturated ethanolamides including arachidonoyl ethanolamide (AEA), DEA, docosatrienoyl ethanolamide (DTEA), eicosatrienoyl ethanolamide (ETEA), eicosapentaenoyl ethanolamide (EPEA) and docosahexaenoyl ethanolamide (DHEA) were higher in the Sub compared with the Dom mice. Untargeted LC/MS analysis showed that the parent fatty acids, docosatetraenoic (DA) and eicosapentaenoic (EPA), were higher in Sub vs. Dom. Gene expression analysis revealed increased mRNA expression of genes encoding the desaturase FADS2 and the elongase ELOVL5 in Sub mice compared with Dom mice. Acute DEA administration at the dose of 15 mg/kg produced antinociceptive and locomotion-inducing effects in Sub mice, but not in Dom mice. Subchronic treatment with DEA at the dose of 5 mg/kg augmented dominant behavior in wild-type ICR and Dom mice but not in Sub mice.Conclusion: This study suggests that the endocannabinoid system may play a role in the regulation of dominance and submissiveness, functional elements of social behavior and personality. While currently we have only scratched the surface, understanding the role of the endocannabinoid system in personality may help in revealing the mechanisms underlying the etiopathology of psychiatric disorders

A delightful trip along the pathway of cannabinoid and endocannabinoid chemistry and pharmacology.

After a traumatic childhood in Europe during the Second World War, I found that scientific research in Israel was a pleasure beyond my expectations. Over the last 65 year, I have worked on the chemistry and pharmacology of natural products. During the last few decades, most of my research has been on plant cannabinoids, the endogenous cannabinoids arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol, and endogenous anandamide-like compounds, all of which are involved in a wide spectrum of physiological reactions. Two plant cannabinoids, Δ-tetrahydrocannabinol and cannabidiol, are approved drugs. However, the endogenous cannabinoids and the anandamide-like constituents have not yet been well investigated in humans. For me, intellectual freedom-the ability to do research based on my own scientific interests-has been the most satisfying part of my working life. Looking back over the 91 years of my long life, I conclude that I have been lucky, very lucky, both personally and scientifically