Cannabinoid Receptor 2: Potential Role in Immunomodulation and Neuroinflammation

Department of Pathology and Laboratory Medicine, Temple University School of Medicine, 3401 N. Broad St., Philadelphia, PA, 19140, USA, .
Journal of Neuroimmune Pharmacology (Impact Factor: 4.11). 03/2013; 8(3). DOI: 10.1007/s11481-013-9445-9
Source: PubMed


An accumulating body of evidence suggests that endocannabinoids and cannabinoid receptors type 1 and 2 (CB1, CB2) play a significant role in physiologic and pathologic processes, including cognitive and immune functions. While the addictive properties of marijuana, an extract from the Cannabis plant, are well recognized, there is growing appreciation of the therapeutic potential of cannabinoids in multiple pathologic conditions involving chronic inflammation (inflammatory bowel disease, arthritis, autoimmune disorders, multiple sclerosis, HIV-1 infection, stroke, Alzheimer's disease to name a few), mainly mediated by CB2 activation. Development of CB2 agonists as therapeutic agents has been hampered by the complexity of their intracellular signaling, relative paucity of highly selective compounds and insufficient data regarding end effects in the target cells and organs. This review attempts to summarize recent advances in studies of CB2 activation in the setting of neuroinflammation, immunomodulation and HIV-1 infection.

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    • "There are at least two types of cannabinoid receptors, CB1 (CNR1) and CB2 (CNR2), both coupled to G proteins. CB2 receptors, the nonpsychoactive cannabinoid receptors, are present mainly on immune cells [7], suggesting that cannabinoids may have an important role in the regulation of the inflammatory response. This suggestion is supported by the observation that cannabinoids effectively suppress immunologic and inflammatory functions of leukocytes in vitro [8] and the reported effect of cannabis in modulating a variety of immune cell functions such as T helper cell development, chemotaxis, and tumor development [9]. "
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    ABSTRACT: We present a case of a 27-year-old man with recurrent episodes of angioedema since he was 19, who responded well to treatment with medical grade cannabis. Initially, he responded to steroids and antihistamines, but several attempts to withdraw treatment resulted in recurrence. In the last few months before prescribing cannabis, the frequency and severity of the attacks worsened and included several presyncope events, associated with scrotal and neck swelling. No predisposing factors were identified, and extensive workup was negative. The patient reported that he was periodically using cannabis socially and that during these periods he was free of attacks. Recent data suggest that cannabis derivatives are involved in the control of mast cell activation. Consequently, we decided to try a course of inhaled cannabis as modulators of immune cell functions. The use of inhaled cannabis resulted in a complete response, and he has been free of symptoms for 2 years. An attempt to withhold the inhaled cannabis led to a recurrent attack within a week, and resuming cannabis maintained the remission, suggesting a cause and effect relationship.
    Full-text · Article · Aug 2015
    • "TRPA1 was found to be activated by CBD (De Petrocellis et al., 2008). The receptor was also shown to be involved in the inhibition of nitric oxide production in macrophages and the amelioration of murine colitis by the plant compound cannabichromene (Romano et al., 2013). "
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    ABSTRACT: From their phylogenetic and pharmacological classification it might be inferred that cannabinoid receptors and their endogenous ligands constitute a rather specialised and biologically distinct signalling system. However, the opposite is true and accumulating data underline how much the endocannabinoid system is intertwined with other lipid and non-lipid signalling systems. Endocannabinoids per se have many structural congeners, and these molecules exist in dynamic equilibria with different other lipid-derived mediators, including eicosanoids and prostamides. With multiple crossroads and shared targets, this creates a versatile system involved in fine-tuning different physiological and metabolic processes, including inflammation. A key feature of this 'expanded' endocannabinoid system, or 'endocannabinoidome', is its subtle orchestration based on interactions between a relatively small number of receptors and multiple ligands with different but partly overlapping activities. Following an update on the role of the 'endocannabinoidome' in inflammatory processes, this review continues with possible targets for intervention at the level of receptors or enzymes involved in formation or breakdown of endocannabinoids and their congeners. Although its pleiotropic character poses scientific challenges, the 'expanded' endocannabinoid system offers several opportunities for prevention and therapy of chronic diseases. In this respect, successes are more likely to come from 'multiple-target' than from 'single-target' strategies. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Aug 2015 · European journal of pharmacology
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    • "All the other elements of eCB system remained unaltered, except for a slight down regulation of NAPE-PLD mRNA. According to a recent hypothesis on autism and inflammation [108], and in keeping with data on the key-role of CB 2 in immune-related pathologies [109] [110] [111], it can be speculated that the increase in CB 2 expression may serve a compensatory role with respect to the inflammatory state associated with autism. Thus, the observed enhancement of CB 2 may be a negative feedback response aimed at counteracting the pro-inflammatory responses implicated in the pathogenesis of this neurobehavioral condition. "
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    ABSTRACT: Autism spectrum disorder (ASD) is a complex behavioral condition with onset during early childhood and a lifelong course in the vast majority of cases. To date, no behavioral, genetic, brain imaging, or electrophysiological test can specifically validate a clinical diagnosis of ASD. However, these medical procedures are often implemented in order to screen for syndromic forms of the disorder (i.e., autism comorbid with known medical conditions). In the last 25 years a good deal of information has been accumulated on the main components of the "endocannabinoid (eCB) system", a rather complex ensemble of lipid signals ("endocannabinoids"), their target receptors, purported transporters, and metabolic enzymes. It has been clearly documented that eCB signaling plays a key role in many human health and disease conditions of the central nervous system, thus opening the avenue to the therapeutic exploitation of eCB-oriented drugs for the treatment of psychiatric, neurodegenerative, and neuroinflammatory disorders. Here we present a modern view of the eCB system, and alterations of its main components in human patients and animal models relevant to ASD. This review will thus provide a critical perspective necessary to explore the potential exploitation of distinct elements of eCB system as targets of innovative therapeutics against ASD.
    Full-text · Article · Jul 2015 · Journal of the American Society for Experimental NeuroTherapeutics
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