Cannabinoids have been proposed as clinically promising neuroprotective molecules, as they are capable to reduce excitotoxicity, calcium influx, and oxidative injury. They are also able to decrease inflammation by acting on glial processes that regulate neuronal survival and to restore blood supply to injured area by reducing the vasoconstriction produced by several endothelium-derived factors. Through one or more of these processes, cannabinoids may provide neuroprotection in different neurodegenerative disorders including Parkinson's disease and Huntington's chorea, two chronic diseases that are originated as a consequence of the degeneration of specific nuclei of basal ganglia, resulting in a deterioration of the control of movement. Both diseases...

Abstract One of the unique features of prenatal alcohol exposure in humans is impaired cognitive and behavioral function resulting from damage to the central nervous system (CNS), which leads to a spectrum of impairments referred to as fetal alcohol spectrum disorder (FASD). Human FASD phenotypes can be reproduced in the rodent CNS following prenatal ethanol exposure. Several mechanisms are expected to contribute to the detrimental effects of prenatal alcohol exposure on the developing fetus, particularly in the developing CNS. These mechanisms may act simultaneously or consecutively and differ among a variety of cell types at specific developmental stages in particular brain regions. Studies have...

Abstract Gliomas constitute the most frequent and malignant primary brain tumors. Current standard therapeutic strategies (surgery, radiotherapy and chemotherapeutics, e.g., temozolomide, carmustin or carboplatin) for their treatment are only palliative and survival diagnosis is normally 6-12 months. The development of new therapeutic strategies for the management of gliomas is therefore essential. Interestingly, cannabinoids have been shown to exert antiproliferative effects on a wide spectrum of cells in culture. Of interest, cannabinoids have displayed a great potency in reducing glioma tumor growth either in vitro or in animal experimental models, curbing the growth of xenografts generated by subcutaneous or intratecal injection of glioma cells in...

The roles of endocannabinoid signaling during central nervous system development are unknown. We report that CB1 cannabinoid receptors (CB1Rs) are enriched in the axonal growth cones of g-aminobutyric acid–containing (GABAergic) interneurons in the rodent cortex during late gestation. Endocannabinoids trigger CB1R internalization and elimination from filopodia and induce chemorepulsion and collapse of axonal growth cones of these GABAergic interneurons by activating RhoA. Similarly, endocannabinoids diminish the galvanotropism of Xenopus laevis spinal neurons. These findings, together with the impaired target selection of cortical GABAergic interneurons lacking CB1Rs, identify endocannabinoids as axon guidance cues and demonstrate that endocannabinoid signaling regulates synaptogenesis and target selection in vivo.

During the last few years, the endocannabinoid system has emerged as a highly relevant topic in the scientific community. Many different regulatory actions have been attributed to endocannabinoids, and their involvement in several pathophysiological conditions is under intense scrutiny. Cannabinoid receptors, named CB1 receptor and CB2 receptor, first discovered as the molecular targets of the psychotropic component of the plant Cannabis sativa, participate in the physiological modulation of many central and peripheral functions. CB2 receptor is mainly expressed in immune cells, whereas CB1 receptor is the most abundant G protein-coupled receptor expressed in the brain. CB1 receptor is expressed in the hypothalamus and the...

Abstract Treatment options for neuropathic pain have limited efficacy and use is fraught with dose-limiting adverse effects. The endocannabinoid system has been elucidated over the last several years, demonstrating a significant interface with pain homeostasis. Exogenous cannabinoids have been demonstrated to be effective in a range of experimental neuropathic pain models, and there is mounting evidence for therapeutic use in human neuropathic pain conditions. This article reviews the history, pharmacologic development, clinical trials results, and the future potential of nonsmoked, orally bioavailable, nonpsychoactive cannabinoids in the management of neuropathic pain.

Cannabis is the most commonly used illicit substance among pregnant women. Human epidemiological and animal studies have found that prenatal cannabis exposure influences brain development and can have long-lasting impacts on cognitive functions. Exploration of the therapeutic potential of cannabis-based medicines and synthetic cannabinoid compounds has given us much insight into the physiological roles of endogenous ligands (endocannabinoids) and their receptors. In this article, we examine human longitudinal cohort studies that document the longterm influence of prenatal exposure to cannabis, followed by an overview of the molecular composition of the endocannabinoid system and the temporal and spatial changes in their expression during brain development....

Recent studies have provided evidence that the endocannabinoid (EC) system has very significant effects on energy balance and metabolism through the central control of appetite and by affecting peripheral metabolism. Endocannabinoids are endogenous phospholipid derivatives which bind and activate cannabinoid receptors type 1 and type 2 (CB1 and CB2 receptors). The CB1 receptor, a G-protein coupled receptor, is believed to be responsible for the majority of the central effects of endocannaboids on appetite. Chronic positive energy balance and obesity have been associated with an overactivation of the endocannaboid system which has been suggested to contribute to the development of abdominal obesity and to associated...

Abstract Cannabinoids form a singular family of plant-derived compounds (phytocannabinoids), endogenous signaling lipids (endocannabinoids), and synthetic derivatives with multiple biological effects and therapeutic applications in the central and peripheral nervous systems. One of these properties is the regulation of neuronal homeostasis and survival, which is the result of the combination of a myriad of effects addressed to preserve, rescue, repair, and/or replace neurons, and also glial cells against multiple insults that may potentially damage these cells. These effects are facilitated by the location of specific targets for the action of these compounds (e.g., cannabinoid type 1 and 2 receptors, endocannabinoid inactivating enzymes, and nonendocannabinoid...

Various lines of (pre)clinical research indicate that cannabinoid agents carry the potential for therapeutic application to reduce symptoms in several psychiatric disorders. However, direct testing of the involvement of cannabinoid brain systems in psychiatric syndromes is essential for further development. In the Pharmacological Imaging of the Cannabinoid System (PhICS) study, the involvement of the endocannabinoid system in cognitive brain function is assessed by comparing acute effects of the cannabinoid agonist Δ9-tetrahydrocannabinol (THC) on brain function between healthy controls and groups of psychiatric patients showing cognitive dysfunction. This article describes the objectives and methods of the PhICS study and presents preliminary results of the administration...