“Cannabinoids modulate intestinal permeability through CB1.
The endocannabinoid-like compounds oleoylethanolamine (OEA) and palmitoylethanolamine (PEA) play an important role in digestive regulation, and we hypothesized they would also modulate intestinal permeability.
OEA and PEA have endogenous roles and potential therapeutic applications in conditions of intestinal hyperpermeability and inflammation.”
“Cannabis enables and enhances the subjective sense of well-being by stimulating the endocannabinoid system (ECS), which plays a key role in modulating the response to stress, reward, and their interactions.
The recent shift toward legalization of medical or recreational cannabis has renewed interest in investigating the physiological role of the ECS as well as the potential health effects, both adverse and beneficial, of cannabis.
Here we review our current understanding of the ECS and its complex physiological roles.
We discuss the implications of this understanding vis-á-vis the ECS’s modulation of stress and reward and its relevance to mental disorders in which these processes are disrupted (i.e., addiction, depression, posttraumatic stress disorder, schizophrenia), along with the therapeutic potential of strategies to manipulate the ECS for these conditions.”
“Pediatric low-grade gliomas (P-LGG) consist of a mixed group of brain tumors that correspond to the majority of CNS tumors in children.
Notably, they may exhibit spontaneous involution after subtotal surgical removal (STR). In this study, we investigated molecular indicators of spontaneous involution in P-LGG.
The P-LGG, which remained stable or that presented spontaneous involution after STR, showed significantly higher CNR1 expression at the time of diagnosis.
We hypothesize that high expression levels of CNR1 provide tumor susceptibility to the antitumor effects of circulating endocannabinoids like anandamide, resulting in tumor involution.
This corroborates with reports suggesting that CNR1 agonists and activators of the endocannabinoid system may represent therapeutic opportunities for children with LGG.
We also suggest that CNR1 may be a prognostic marker for P-LGG.
This is the first time spontaneous involution of P-LGG has been suggested to be induced by endocannabinoids.”
“Since the discovery of the endocannabinoid system consisting of cannabinoid receptors, endogenous ligands, and biosynthetic and metabolizing enzymes, interest has been renewed in investigating the promise of cannabinoids as therapeutic agents.
Abundant evidence indicates that cannabinoids modulate immune responses.
An inflammatory response is triggered when innate immune cells receive a danger signal provided by pathogen- or damage-associated molecular patterns engaging pattern-recognition receptors.
Toll-like receptor family members are prominent pattern-recognition receptors expressed on innate immune cells.
Cannabinoids suppress Toll-like receptor-mediated inflammatory responses.
Innate immune cells express cannabinoid receptors and produce endogenous cannabinoids.
Hence, innate immune cells may play a role in regulating endocannabinoid homeostasis, and, in turn, the endocannabinoid system modulates local inflammatory responses.
Studies designed to probe the interaction between the innate immune system and the endocannabinoid system may identify new potential molecular targets in developing therapeutic strategies for chronic inflammatory diseases.
This review discusses the endocannabinoid system and Toll-like receptor family and evaluates the interaction between them.”
“2-Arachidonylglycerol (2-AG) inhibits the production in vitro of tumor necrosis factor-alpha (TNF-alpha) by mouse macrophages, as well as in mice. It has no effect on the production of nitric oxide (NO). The effect on TNF-alpha is enhanced when 2-AG is administered together with 2-linoleylglycerol (2-Lino-G) and 2-palmitylglycerol (2-PalmG), an ‘entourage effect’ previously noted in several behavioral and binding assays. 2-AG also suppresses the formation of radical oxygen intermediates.”
“The relationship between cannabinoid receptor signaling and psychosis vulnerability requires further exploration.
The endocannabinoid signaling system is extensive, with receptors exerting regulatory functions in both immune and central nervous systems.
In the brain, cannabinoid receptors (CBR) directly modulate neurotransmitter systems.
In the peripheral lymphocyte, CBRs mediate cytokine release, with dysregulated cytokine levels demonstrated in schizophrenia.
These results continue to support dysregulation of particular aspects of the endocannabinoid signaling system in participants with schizophrenia selected for the self-reported absence of marijuana abuse/dependence.”
http://www.ncbi.nlm.nih.gov/pubmed/27591408
“Mood disorders, including anxiety and depression, are frequently diagnosed in multiple sclerosis (MS) patients, even independently of the disabling symptoms associated with the disease.
Anatomical, biochemical, and pharmacological evidence indicates that type-1 cannabinoid receptor (CB1R) is implicated in the control of emotional behavior and is modulated during inflammatory neurodegenerative diseases such as MS and experimental autoimmune encephalomyelitis (EAE).
Collectively, our data contribute to clarify the synaptic and, at least in part, molecular basis of mood disturbances in EAE and, possibly, MS. Understanding the neurobiological underpinning of anxiety-like behavior in EAE mice is of crucial importance to optimize the treatment of mood disturbance in MS and, possibly, other neuroinflammatory diseases.
In this direction, targeting the endocannabinoid system may be a valid therapeutic tool for the treatment of both psychiatric and motor symptoms in MS patients.”
“Compared with acute pain that arises suddenly in response to a specific injury and is usually treatable, chronic pain persists over time, and is often resistant to medical treatment.
Because of the heterogeneity of chronic pain origins, satisfactory therapies for its treatment are lacking, leading to an urgent need for the development of new treatments.
The leading approach in drug design is selective compounds, though they are often less effective and require chronic dosing with many side effects.
Herein, we review novel approaches to drug design for the treatment of chronic pain represented by dual-acting compounds, which operate at more than one biological target.
A number of studies suggest the involvement of the cannabinoid and vanilloid receptors in pain.
Interestingly cannabinoid system is in interrelation with other systems that comprise lipid mediators: prostaglandins, produced by COX enzyme.
Therefore, in the present review, we summarize the role of dual-acting molecules (FAAH/TRPV1 and FAAH/COX-2 inhibitors) that interact with endocannabinoid and endovanillinoid systems and act as analgesics by elevating the endogenously produced endocannabinoids and dampening the production of pro-inflammatory prostaglandins.
The plasticity of the endocannabinoid system (ECS) and the ability of a single chemical entity to exert an activity on two receptor systems has been developed and extensively investigated.
Here, we review up-to-date pharmacological studies on compounds interacting with FAAH enzyme together with TRPV1 receptor or COX-2 enzyme respectively.
Multi-target pharmacological intervention for treating pain may lead to the development of original and efficient treatments.”
“A growing body of psychiatric research has emerged, focusing on the role of endocannabinoid system in psychiatric disorders.
For example, the endocannabinoid system, via cannabinoid CB (CB1 and CB2) receptors, is able to control the function of many receptors, such as N-methyl-D-aspartate (NMDA) receptors connected strictly with psychosis or other schizophrenia-associated symptoms.
The aim of the present research was to investigate the impact of the CB1 receptor ligands on the symptoms typical for schizophrenia.
The present findings confirm that endocannabinoid system is able to modify a variety of schizophrenia-like responses, including the cognitive disturbances and hyperlocomotion in mice.
Antipsychotic-like effects induced by CB1 receptor antagonist, obtained in our research, confirm the potential effect of CB1 receptor blockade and could have important therapeutic implications on clinical settings, in the future.”
“Peltatoside is a natural compound isolated from leaves of Annona crassiflora Mart., a plant widely used in folk medicine.
This substance is an analogue of quercetin, a flavonoid extensively studied because of its diverse biological activities, including analgesic effects. Besides, a previous study suggested, by computer structure analyses, a possible quercetin-CB1 cannabinoid receptor interaction.
Thus, the aim of this work was to assess the antinociceptive effect of peltatoside and analyze the cannabinoid system involvement in this action.
Our results suggest that this natural substance is capable of inducing analgesia through the activation of peripheral CB1 receptors, involving endocannabinoids in this process.”
http://www.ncbi.nlm.nih.gov/pubmed/27574895
