Endocannabinoids And Lipid Mediators In Brain Functions

The science of cannabinoids is 50 years old. These past years provided a remarkable and constant number of breakthroughs, showing that the signaling mediated by endocannabinoids and lipid mediators impacts almost every function of the body. Indeed, this represents a special field of research, which allows tackling the complexity of biological functions, and provides potential therapeutic frameworks for a plethora of diseases. The number of exciting discoveries brought up to the scientific community almost on a daily basis highlights the importance of an updated volume on this topic. Particularly, given that potential therapeutic benefits of cannabis and cannabinoids are currently under heavy analysis in many Countries worldwide. Hence, the main objective of this book is to explore not only some of the many functions of endocannabinoids (and lipid mediators) in physiological control of networks at a cellular and molecular level, but also to extend this knowledge for potential use of cannabinoids and/or drugs regulating endocannabinoid levels in vivo as therapeutic target(s) in neurological and neuropsychiatric disorders. In this book new findings and ideas about the endocannabinoid system and its roles as neuronal circuit modulator related to human brain pathologies characterized by alterations in neuroplasticity will be highlighted. Endocannabinoid roles in key systems controlling appetite, pain, learning and memory, as well as sleep and stress responses will be presented. In addition, pathological processes associated with changes in endocannabinoid signaling will be discussed in the context of anxiety, autism, depression and addiction. This book will provide an excellent background to researchers looking for extending their areas of interest, and to newcomers in the field.

The Endocannabinoidome: The World of Endocannabinoids and Related Mediators is dedicated to the latest research and studies on endocannabinoids and cannabinoid receptors to illustrate their important role in the discovery of new, endocannabinoid-related, lipid mediators. Written by leading experts across different disciplines, this book focuses on the biochemical and anlayticial aspects of novel lipid signals, their pharmacological activities and their potential utilization for the development of new and effective therapeutic strategies. The first book of its kind, The Endocannabinoidome is a meaningful reference for all those involved in experimental efforts to further the development of this field. Explores the novel and exciting aspects of several endocannabinoid-like molecules for which researchers are still seeking a function Discusses the novel metabolic pathways for endocannabinoids in order to explain the failure of some clinical trials with inhibitors of more conventional metabolic pathways Incorporates pharmacology, biochemistry and potential clinical applications to provide researchers with a complete look at endocannabinoids

In Europe, approximately one in five adults experience chronic pain, pain that lasts more than three months. Chronic pain is a significant problem not only for those people suffering from chronic pain but also for society. The prevalence of chronic pain is higher in women and lower socioeconomic groups. Although chronic pain often originates in a specific site, it may eventually spread to several sites, transforming into chronic widespread pain (CWP), a condition evident in about 10% of the adult population. Approximately 1.2-5.4% are classified with fibromyalgia (FM). In addition to CWP, common symptoms of FM include, stiffness, fatigue, sleep disturbances, and cognitive dysfunction and common co-morbidities include depression and anxiety. Although FM/CWP has been reported to alter both central and peripheral nociceptive mechanisms, no objective biomarkers have been found that correlate with CWP/FM and no standard examinations such as blood test, X-ray or computed tomography can provide support for a diagnosis. Because there are no objective biomarkers that correlate with the pathophysiological processes associated with CWP/FM, this debilitating disease is difficult to diagnose and ultimately treat. However, there are some promising therapeutic targets for chronic pain with inter alia analgesic, anti-inflammatory, and stress modulating properties: the endocannabinoids (ECs) arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG) and their related lipids oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA). This thesis investigates whether ECs and the related N-acylethanolamines (NAEs) can be used as potential biomarkers for CWP/FM. Specifically, the studies compared the peripheral and systemic levels of ECs and NAEs in 121 women with CWP/FM and in 137 healthy controls in two different cohorts. In addition, the correlation between lipid levels and common pain characteristics such as intensity, sensitivity, and duration were investigated. The EC and related lipid levels were measured using liquid chromatography in combination with tandem mass spectrometry. Multivariate data analysis was used for biomarker evaluation. Compared to the healthy controls, the CWP/FM patients had significantly higher concentrations of OEA, PEA, and SEA in muscle and plasma (p ? 0.05) and significantly higher 2-AG in plasma (p ? 0.01). These results may indicate that NAEs, are mobilized differently in painful muscles compared with pain free muscles. Moreover, increased systemic levels of NAEs and 2-AG in patients might be signs of ongoing low-grade inflammation in CWP/FM. These findings contribute to a better understanding of how peripheral and systemic factors maintain and activate chronic pain. Although the investigated lipids have statistically significant effects but biologically uncertain role in the clinical manifestations of CWP/FM. Thus plasma lipids are not a good biomarker for CWP/FM. Nevertheless, increased lipid levels indicate a metabolic asymmetry in CWP/FM, a finding that could serve as a basis for more research on pain management.

Over the past decade, there have been major advances in understanding the mechanisms whereby marijuana interacts with the brain in producing psychoactive and potentially therapeutic effects. The discovery of specific gene coding for cannabinoid receptors activated by smoking marijuana, and the finding of endogenous cannabinoids, which also activate the receptors, have transformed cannabinoid research into mainstream science with significant implications in human health and disease Endocannabinoids: The Brain and Body’s Marijuana and Beyond documentsadvances in the discovery and functioning of naturally occurring marijuana-like substances in human biology. It explores recent findings that point to the existence of an endocannabinoid physiological control system (EPCS) that directly impacts human development, health, and disease. While cannabinoid effects on the brain have received the greatest attention throughout the literature, this work looks at research on the endogenous cannabinoid system’s association across all of human physiology, including the immune, endocrine, and reproductive systems. With thoroughly researched and exceptionally insightful contributions from more than three-dozen top-flight researchers representing a cross-section of disciplines from molecular biology, genetics, and neurology to gynecology, physiology, and pharmacology, this work explores a range of topics as wide as the human body is complex. These topics include the EPCS’s relation to cell development and regulation, CNS function, immune function modulation, reproduction, and digestion, as well as its function in mental illness, neurodegenerative diseases, and cancer. The final section in the book considers the significance of endogenous cannabinoids found in some of the simplest multicellular organisms in the animal kingdom, as well as in mammalian cells at the earliest stages of development, all of which suggests that they play a fundamental role in human biology. Enocannabinoids: The Brain and Body’s Marijuana and Beyond explores areas that few books have ventured into, providing cutting-edge information that will ultimately help us better understand human biology at the systemic and perhaps even cellular level, as well as lead to the development of a whole new range of medications.

This book provides a comprehensive overview of current knowledge of cannabinoid activity in human physiology and points out the importance of endocannabinoid system for the maintenance of human health and treatment of diseases. Each chapter has been organized with the aim to cover basic concepts in the modulation of endocannabinoid system in both physiological and pathological conditions, thanks to the integration of data from experimental animal models and clinical observations. A special focus has been put on the medical use of cannabinoids and on the targeting of endocannabinoid system as new therapeutic strategy for the prevention and treatment of human diseases. Taken together, this book targets a wide audience of basic and clinical scientists, teachers and students interested in gaining a better understanding in the field of cannabinoids.

Edited and authored by a wealth of international experts in neuroscience and related disciplines, this key new resource aims to offer medical students and graduate researchers around the world a comprehensive introduction and overview of modern neuroscience. Neuroscience research is certain to prove a vital element in combating mental illness in its various incarnations, a strategic battleground in the future of medicine, as the prevalence of mental disorders is becoming better understood each year. Hundreds of millions of people worldwide are affected by mental, behavioral, neurological and substance use disorders. The World Health Organization estimated in 2002 that 154 million people globally suffer from depression and 25 million people from schizophrenia; 91 million people are affected by alcohol use disorders and 15 million by drug use disorders. A more recent WHO report shows that 50 million people suffer from epilepsy and 24 million from Alzheimer’s and other dementias. Because neuroscience takes the etiology of disease—the complex interplay between biological, psychological, and sociocultural factors—as its object of inquiry, it is increasingly valuable in understanding an array of medical conditions. A recent report by the United States’ Surgeon General cites several such diseases: schizophrenia, bipolar disorder, early-onset depression, autism, attention deficit/ hyperactivity disorder, anorexia nervosa, and panic disorder, among many others. Not only is this volume a boon to those wishing to understand the future of neuroscience, it also aims to encourage the initiation of neuroscience programs in developing countries, featuring as it does an appendix full of advice on how to develop such programs. With broad coverage of both basic science and clinical issues, comprising around 150 chapters from a diversity of international authors and including complementary video components, Neuroscience in the 21st Century in its second edition serves as a comprehensive resource to students and researchers alike.

With recent studies using genetic, epigenetic, and other molecular and neurochemical approaches, a new era has begun in understanding pathophysiology of suicide. Emerging evidence suggests that neurobiological factors are not only critical in providing potential risk factors but also provide a promising approach to develop more effective treatment and prevention strategies. The Neurobiological Basis of Suicide discusses the most recent findings in suicide neurobiology. Psychological, psychosocial, and cultural factors are important in determining the risk factors for suicide; however, they offer weak prediction and can be of little clinical use. Interestingly, cognitive characteristics are different among depressed suicidal and depressed nonsuicidal subjects, and could be involved in the development of suicidal behavior. The characterization of the neurobiological basis of suicide is in delineating the risk factors associated with suicide. The Neurobiological Basis of Suicide focuses on how and why these neurobiological factors are crucial in the pathogenic mechanisms of suicidal behavior and how these findings can be transformed into potential therapeutic applications.