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Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor

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Arachidonylethanolamide, an arachidonic acid derivative in porcine brain, was identified in a screen for endogenous ligands for the cannabinoid receptor. The structure of this compound, which has been named "anandamide," was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by synthesis. Anandamide inhibited the specific binding of a radiolabeled cannabinoid probe to synaptosomal membranes in a manner typical of competitive ligands and produced a concentration-dependent inhibition of the electrically evoked twitch response to the mouse vas deferens, a characteristic effect of psychotropic cannabinoids. These properties suggest that anandamide may function as a natural ligand for the cannabinoid receptor.
... Por otra parte, la distribución de receptores CB2 en distintas células del sistema inmune, explica el efecto inmunosupresor de la marihuana. (Devane et al, 1992). ...
... El Tetrahidrocannabinol, comúnmente conocido como THC es el componente psicoactivo (alteración de la percepción y modificación del estado de ánimo) de la planta de cannabis más importante y abundante en las variedades clasificadas precisamente como psicoactivas (Devane et al, 1992). ...
... Devane et al, 1992). Se considera pues como un sistema de señalización implicado en numerosos procesos como el apetito, el movimiento, el dolor, procesos de morbilidades, etc.El uso del cannabis estuvo prohibido internacionalmente desde 1961 bajo la Convención Única de Estupefacientes y solo hasta el 2020 se reconoció internacionalmente como una planta con propiedades medicinales. ...
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Los diferentes usos del cannabis han tenido un crecimiento en los últimos años, donde la producción mundial de cannabis con fines medicinales incrementó de 100 toneladas en 2015 a 406 toneladas en 2017 (JIFE, 2018). Se estima que alrededor de 30 países han legalizado alguna de sus formas de producción y/o comercialización del cannabis, incluso con fines recreativos, en algunos de los casos (Global Markets - EY Knowledge, 2018). Así mismo, en la literatura se destacan los logros alcanzados en los desarrollos dentro de la industria del cannabis para uso medicinal que impacta positivamente en la economía de los países que han incursionado en el tema. Respecto al ámbito local, en Colombia se observa un camino recorrido y las posibilidades de ahondar en los usos medicinales de cannabis que podrían situar al país en un lugar preponderante y de gran potencial en el desarrollo de esta industria y en su posicionamiento internacional. Para lo cual, existe un marco regulatorio colombiano que abre el acceso al cannabis con fines médicos y científicos.
... Endocannabinoids (eCBs), such as N-arachidonoylethanolamine (anandamide, AEA; Devane et al., 1992) and 2-arachidonoylglycerol (2-AG; Mechoulam et al., 1995;Sugiura et al., 1995), are a group of endogenous lipid mediators and neurotransmitters that are released "on demand. " eCB signalling is controlled in part by selective eCB-degrading enzymes, such as fatty acid amide hydrolase (FAAH), which is responsible for the degradation of AEA and monoacylglycerol lipase (MAGL), involved in the degradation of 2-AG (Egertová et al., 1998;Romero et al., 2002;Maccarrone, 2017). ...
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Several studies in both animal models and in humans have provided substantial evidence that early life stress (ELS) induces long-term changes in behavior and brain function, making it a significant risk factor in the aetiology of various mental disorders, including anxiety and depression. In this study, we tested the hypothesis that ELS in male rats (i) leads to increased anxiety and depressive-like symptoms; and (ii) that these behavioral changes are associated with functional alterations in the endocannabinoid system of the medial prefrontal cortex (mPFC). We further assessed whether the predicted changes in the gene expression of two key components of the endocannabinoid system, cannabinoid receptor 1 (CB1R) and the fatty acid amide hydrolase (FAAH), are regulated by epigenetic mechanisms. Behavioral profiling revealed that the proportion of behaviorally affected animals was increased in ELS exposed male rats compared to control animals, specifically showing symptoms of anhedonia and impaired social behavior. On the molecular level we observed a decrease in CB1R and FAAH mRNA expression in the mPFC of adult ELS exposed animals. These gene expression changes were accompanied by reduced global histone 3 acetylation in the mPFC, while no significant changes in DNA methylation and no significant changes of histone-acetylation at the promoter regions of the analyzed genes were detected. Taken together, our data provide evidence that ELS induces a long-term reduction of CB1R and FAAH expression in the mPFC of adult male rats, which may partially contribute to the ELS-induced changes in adult socio-emotional behavior.
... Our results from fiber-optic recordings of eCB2.0 fluorescence dynamics confirmed this in the MGB and MD. eCBs are signaling lipids that activate cannabinoid receptors [86][87][88][89] . Cannabinoid receptors are divided into two classes: CB1R, which is located primarily in the brain 90,91 , and cannabinoid 2 receptors (CB2R), which is located mainly in immune cells in the periphery 92 . ...
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Tinnitus has been identified as a potential contributor to anxiety. Thalamo-cortical pathway plays a crucial role in the transmission of auditory and emotional information, but its casual link to tinnitus-associated anxiety remains unclear. In this study, we explore the neural activities in the thalamus and cortex of the sodium salicylate (NaSal)-treated mice, which exhibit both hyperacusis and anxiety-like behaviors. We find an increase in gamma band oscillations (GBO) in both auditory cortex (AC) and prefrontal cortex (PFC), as well as phase-locking between cortical GBO and thalamic neural activity. These changes are attributable to a suppression of GABAergic neuron activity in thalamic reticular nucleus (TRN), and optogenetic activation of TRN reduces NaSal-induced hyperacusis and anxiety-like behaviors. The elevation of endocannabinoid (eCB)/ cannabinoid receptor 1 (CB1R) transmission in TRN contributes to the NaSal-induced abnormalities. Our results highlight the regulative role of TRN in the auditory and limbic thalamic-cortical pathways.
... In addition, several orphan G protein-coupled receptors (GPR18, GPR55, and GPR119), transient receptor potential channels (TRPV1, TRPV2, TRPV3, TRPV4, TRPM8, and TRPA1), and peroxisome proliferatoractivated receptors (PPARα and PPARγ) that mediate the effects of cannabinoids are distributed in the skin [21][22][23][24][25]. The expression of N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), the major endocannabinoids, along with their anabolic and catabolic enzymes (e.g., N-acylphosphatidylethanolamine phospholipase D [NAPE-PLD], diacylglycerol lipases [DAGLα and DAGLβ], fatty acid amide hydrolase [FAAH], and monoacylglycerol lipase [MAGL]) are also found in the skin [20,[26][27][28]. These data support the notion that the skin has its own ECS consisting of endocannabinoids, cannabinoid receptors, and metabolic enzymes for endocannabinoids ( Fig. 1) [8]. ...
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Cannabidiol (CBD) is a non-psychotropic cannabinoid with multiple pharmacological properties. Cannabidiol has attracted growing attention in the cosmetic industry, with an increasing number of CBD-containing skincare products on the market in recent years. The aim of this review is to evaluate the current evidence on the use of CBD for cosmetic purposes. Following an overview of CBD and the endocannabinoid system in the skin, we summarize pre-clinical and clinical studies that address the potential of CBD in cosmetic dermatology. Available in vitro and in vivo evidence suggests that CBD has anti-oxidant, anti-inflammatory, moisturizing, anti-acne, wound-healing, and anti-aging properties. However, only a few clinical studies have been conducted on the use of CBD in the skin. In addition, there is a critical need to develop an efficient drug-delivery system for topical/transdermal application of CBD. Further research, including clinical and pharmacokinetic studies, are needed to fully evaluate the role of CBD in cosmetic dermatology.
... 17,21 The biological and pharmacological study of Cannabis gained Cannabinoids exert their influence in biological systems by binding to specific receptors, namely cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). [25][26][27] The discovery of endogenous cannabinoids or endocannabinoids, such as anandamide or arachidonoylethanolamide (AEA) and 2-arachidonylglycerol in the 1990s ( Figure 2). 28,29 has shed light on how cannabinoids like THC and CBD interact with cannabinoid receptors and influence biological processes in individuals consuming marijuana. ...
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Cannabinoids' therapeutic potential has garnered significant attention worldwide, with studies displaying their remarkable effectiveness in treating a variety of ailments. These compounds are known for their anti-inflammatory and neuroprotective properties, leading to investigations into their antipsychotic, anxiolytic, and anticonvulsant properties. This narrative review aims to provide an up-to-date overview of the primary therapeutic applications of cannabinoids and their outcomes. We conducted an extensive search across three databases: PubMed, Google Scholar, and Scopus, selecting relevant materials following the PRISMA 2020 guidelines for systematic reviews, while recognizing that this review adopts a narrative approach. Cannabis, a plant with psychotropic attributes, has been subject to strict legal restrictions since the early 20th century, rooted in religious, socio-cultural, and political principles. Nevertheless, cannabinoids derived from the plant offer substantial therapeutic potential, particularly as adjuncts in pain management. Moreover, their efficacy has been demonstrated in various conditions, including respiratory, metabolic, immunological, and neurodegenerative disorders like Parkinson's and Alzheimer's. Recognizing the significance of the Cannabis plant in scientific research is crucial, as it paves the way for safer therapeutic alternatives with minimal side effects. Therefore, facilitating and prioritizing its study across various medical disciplines is essential.
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A potent, synthetic cannabinoid was radiolabeled and used to characterize and precisely localize cannabinoid receptors in slide-mounted sections of rat brain and pituitary. Assay conditions for 3H-CP55,940 binding in Tris-HCl buffer with 5% BSA were optimized, association and dissociation rate constants determined, and the equilibrium dissociation constant (Kd) calculated (21 nM by liquid scintillation counting, 5.2 nM by quantitative autoradiography). The results of competition studies, using several synthetic cannabinoids, add to prior data showing enantioselectivity of binding and correlation of in vitro potencies with potencies in biological assays of cannabinoid actions. Inhibition of binding by guanine nucleotides was selective and profound: Nonhydrolyzable analogs of GTP and GDP inhibited binding by greater than 90%, and GMP and the nonhydrolyzable ATP analog showed no inhibition. Autoradiography showed great heterogeneity of binding in patterns of labeling that closely conform to cytoarchitectural and functional domains. Very dense 3H-CP55,940 binding is localized to the basal ganglia (lateral caudate-putamen, globus pallidus, entopeduncular nucleus, substantia nigra pars reticulata), cerebellar molecular layer, innermost layers of the olfactory bulb, and portions of the hippocampal formation (CA3 and dentate gyrus molecular layer). Moderately dense binding is found throughout the remaining forebrain. Sparse binding characterizes the brain stem and spinal cord. Densitometry confirmed the quantitative heterogeneity of cannabinoid receptors (10 nM 3H-CP55,940 binding ranged in density from 6.3 pmol/mg protein in the substantia nigra pars reticulata to 0.15 pmol/mg protein in the anterior lobe of the pituitary). The results suggest that the presently characterized cannabinoid receptor mediates physiological and behavioral effects of natural and synthetic cannabinoids, because it is strongly coupled to guanine nucleotide regulatory proteins and is discretely localized to cortical, basal ganglia, and cerebellar structures involved with cognition and movement.
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