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  • Endocannabinoid system, Endocannabinoid/s
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Maternal Immune Activation and the Endocannabinoid System: Focus on Two-Hit Models of Schizophrenia

Abstract The devastating effects of the COVID-19 pandemic have underscored the significant threat that infectious diseases pose to our society. Pregnancy represents a period of heightened vulnerability to infections, which can compromise maternal health and increase the risk of neurodevelopmental disorders in offspring. Preclinical and clinical investigations suggest a potential association between maternal immune activation (MIA), which is triggered by viral or bacterial infections, and increased risk for neurodevelopmental disorders such as autism and schizophrenia. Genetic and environmental factors may contribute to the overall risk. Therefore, the two-hit hypothesis of schizophrenia suggests that MIA could act as a first trigger, with subsequent factors, such...
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Amyotrophic Lateral Sclerosis, the Endocannabinoid System, and Exogenous Cannabinoids: Current State and Clinical Implications

Please use this link to access this publication. ABSTRACT A unifying mechanistic cause for amyotrophic lateral sclerosis (ALS) remains uncertain. Multiple pathophysiological processes appear to occur simultaneously. Cannabinoids, including delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), cannabigerol (CBG), and others found in cannabis, and cannabis extracts (CEs), appear to have activity in these pathogenic pathways, which have led to increasing interest in cannabinoids as therapeutic agents for ALS. The use of cannabinoids as a treatment strategy is substantiated by preclinical evidence suggesting a role for the endocannabinoid system (ECS) in ALS and other neurodegenerative disorders. Preclinical data indicate that cannabis and CEs have powerful antioxidative, anti-inflammatory, and...
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Cannabinoids and the male reproductive system: Implications of endocannabinoid signaling pathways

Please use this link to access this publication. Abstract The escalating use and legalization of cannabis (marijuana) in the United States reflect shifting societal attitudes and growing awareness of its potential therapeutic benefits. Historically viewed as a harmful psychoactive substance, contemporary research has shown the intricate pharmacology of cannabis, with its diverse array of cannabinoids and their interactions with the endocannabinoid system. Among these cannabinoids, Δ9-tetrahydrocannabinol is the primary psychoactive component, characterized by its activation of cannabinoid receptors. The discovery of endocannabinoids, including anandamide and 2-arachidonoylglycerol, illuminated the body's innate cannabinoid signaling pathways and their involvement in several physiological processes. Endocannabinoids exert both positive...
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Cannabis, Endocannabinoids and Brain Development: From Embryogenesis to Adolescence

Abstract The endocannabinoid signalling system (ECS) plays a critical role from the very beginning of embryogenesis. Accordingly, the ECS is engaged early on in nervous system development, starting from neurulation, supported by the identification of ECS components—both receptors and enzymes controlling endocannabinoid metabolism—at these early stages. In particular, regarding the brain, the ECS is involved in the tightly regulated sequence of events that comprise brain development, from neurogenesis to neuronal migration, morphological guidance for neuronal connectivity, and synaptic circuitry refinement. The importance of this broad role of the ECS across various brain development processes is further underscored by the growing understanding of the consequences...
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Cannabinoids and the endocannabinoid system in reward processing and addiction: from mechanisms to interventions


Abstract The last decades have seen a major gain in understanding the action of cannabinoids and the endocannabinoid system in reward processing and the development of addictive behavior. Cannabis-derived psychoactive compounds such as Δ9-tetrahydrocannabinol and synthetic cannabinoids directly interact with the reward system and thereby have addictive properties. Cannabinoids induce their reinforcing properties by an increase in tonic dopamine levels through a cannabinoid type 1 (CB1) receptor–dependent mechanism within the ventral tegmental area. Cues that are conditioned to cannabis smoking can induce drug-seeking responses (ie, craving) by eliciting phasic dopamine events. A dopamine-independent mechanism involved in drug-seeking responses involves an endocannabinoid/glutamate interaction within the...
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Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain

Abstract Neuropathic pain conditions including neuropathic orofacial pain (NOP) are difficult to treat. Contemporary therapeutic agents for neuropathic pain are often ineffective in relieving pain and are associated with various adverse effects. Finding new options for treating neuropathic pain is a major priority in pain-related research. Cannabinoid-based therapeutic strategies have emerged as promising new options. Cannabinoids mainly act on cannabinoid 1 (CB1) and 2 (CB2) receptors, and the former is widely distributed in the brain. The therapeutic significance of cannabinoids is masked by their adverse effects including sedation, motor impairment, addiction and cognitive impairment, which are thought to be mediated by CB1 receptors in...
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Cannabinoids, Endocannabinoids and Sleep

ABSTRACT Sleep is a vital function of the nervous system that contributes to brain and bodily homeostasis, energy levels, cognitive ability, and other key functions of a variety of organisms. Dysfunctional sleep induces neural problems and is a key part of almost all human psychiatric disorders including substance abuse disorders. The hypnotic effects of cannabis have long been known and there is increasing use of phytocannabinoids and other formulations as sleep aids. Thus, it is crucial to gain a better understanding of the neurobiological basis of cannabis drug effects on sleep, as well as the role of the endogenous cannabinoid system in sleep physiology....
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The Chemistry of Cannabis and Cannabinoids

Abstract The science of cannabis and cannabinoids encompasses a wide variety of scientific disciplines and can appear daunting to newcomers to the field. The encroachment of folklore and ‘cannabis culture’ into scientific discussions can cloud the situation further. This Primer Review is designed to give a succinct overview of the chemistry of cannabis and cannabinoids. It is hoped that it will provide a useful resource for chemistry undergraduates, postgraduates and their instructors, and experienced chemists who require a comprehensive and up to date summary of the field. The Review begins with a brief overview of the history and botany of cannabis, then goes on...
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Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment

Abstract: Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes. The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson’s disease, Tourette’s syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been proven so far, results from the affinity of these compounds predominantly for the receptors of the endocannabinoid system (the cannabinoid receptor type 1 (CB1), type two (CB2), and the G protein-coupled receptor 55 (GPR55)) but, also, for peroxisome proliferator activated...
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The Behavioral Sequelae of Cannabis Use in Healthy People: A Systematic Review

Abstract Background: Cannabis is known to have a broad range of effects on behavior, including experiencing a “high” and tranquility/relaxation. However, there are several adverse behavioral sequalae that can arise from cannabis use, depending on frequency of use, potency (e.g., THC content), age of onset, and cumulative exposure. This systematic review examined evidence for cannabis-related adverse behavioral sequalae in otherwise healthy human subjects. Methods: Following PRISMA guidelines, we conducted a systematic review of cross-sectional and longitudinal studies from 1990 to 2020 that identified cannabis-related adverse behavioral outcomes in subjects without psychiatric and medical co-morbidities from PubMed and PsychInfo searches. Key search terms included “cannabis”...
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