“Activation of cannabinoid receptor 2 (CB2R) ameliorates inflammation, but the underlying mechanism remains unclear.
In the present study, we examined whether activation of CB2R could suppress the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome.
We conclude that activation of CB2R ameliorates DSS-induced colitis through enhancing autophagy that may inhibit NLRP3 inflammasome activation in macrophages.”
“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.”
“Dexanabinol, HU-211, a synthetic cannabinoid devoid of psychotropic effects, improves neurological outcome in models of brain trauma, ischemia and meningitis.
Recently, HU-211 was found to inhibit brain tumor necrosis factor (TNFalpha) production after head injury. In the present study, we demonstrate the ability of HU-211 to suppress TNFalpha production and to rescue mice and rats from endotoxic shock after LPS (Escherichia coli 055:B5) inoculation.
Administration of LPS to Sprague-Dawley rats resulted in a 30% reduction in the mean arterial blood pressure within 30 min, which persisted for 3 hr. HU-211, given 2 to 3 min before LPS, completely abolished the typical hypotensive response. Furthermore, the drug also markedly suppressed in vitro TNFalpha production and nitric oxide generation (by >90%) by both murine peritoneal macrophages and rat alveolar macrophage cell line exposed to LPS.
HU-211 may, therefore, have therapeutic implications in the treatment of TNFalpha-mediated pathologies.”
“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.”
“Proliferative vitreoretinopathy (PVR) can develop after ocular trauma or inflammation and is a common complication of surgery to correct retinal detachment.
Currently, there are no pharmacological treatments for PVR.
Cannabinoids acting at cannabinoid 2 receptor (CB2R) can decrease inflammation and fibrosis.
The objective of this study was to examine the anti-inflammatory actions of CB2R as a candidate novel therapeutic target in experimental PVR.
In conclusion, our results indicate that intervention at early stage PVR with CB2R agonists reduces ocular inflammation and disease severity.
CB2R may represent a therapeutic target to prevent PVR progression and vision loss.”
“Neurogenic inflammation is a local inflammatory response that is driven by the peripheral release of neuropeptides from small diameter afferents which occurs in many organs including joints.
The knee joint has a rich endocannabinoid system which has been shown to decrease acute synovitis.
The aim of this study was to investigate the influence of joint afferents on leukocyte-endothelial interactions within the synovial microcirculation of mice and determine the role of endocannabinoids on this inflammatory response.
These results provide evidence that antidromic stimulation of the mouse saphenous nerve promotes leukocyte rolling within the synovial microcirculation, and that endocannabinoids can attenuate this neurogenic inflammatory response.”
“In ancient medicine, extracts of the marijuana plant Cannabis sativa were used against diseases of the gastrointestinal (GI) tract.
Today, our knowledge of the ingredients of the Cannabis plant has remarkably advanced enabling us to use a variety of herbal and synthetic cannabinoid (CB) compounds to study the endocannabinoid system (ECS), a physiologic entity that controls tissue homeostasis with the help of endogenously produced CBs and their receptors.
After many anecdotal reports suggested beneficial effects of Cannabis in GI disorders, it was not surprising to discover that the GI tract accommodates and expresses all the components of the ECS.
Cannabinoid receptors and their endogenous ligands, the endocannabinoids, participate in the regulation of GI motility, secretion, and the maintenance of the epithelial barrier integrity.
In addition, other receptors, such as the transient receptor potential cation channel subfamily V member 1 (TRPV1), the peroxisome proliferator-activated receptor alpha (PPARα) and the G-protein coupled receptor 55 (GPR55), are important participants in the actions of CBs in the gut and critically determine the course of bowel inflammation and colon cancer.
The following review summarizes important and recent findings on the role of CB receptors and their ligands in the GI tract with emphasis on GI disorders, such as irritable bowel syndrome, inflammatory bowel disease, and colon cancer.”
“The endocannabinoid system mainly consists of endogenously produced cannabinoids (endocannabinoids) and two G protein-coupled receptors (GPCRs), cannabinoid receptors 1 and 2 (CB1 and CB2). This system also includes enzymes responsible for the synthesis and degradation of endocannabinoids and molecules required for the uptake and transport of endocannabinoids. In addition, endocannabinoid-related lipid mediators and other putative endocannabinoid receptors, such as transient receptor potential channels and other GPCRs have been identified. Accumulating evidence indicates that the endocannabinoid system is a key modulator of gastrointestinal physiology, influencing satiety, emesis, immune function, mucosal integrity, motility, secretion, and visceral sensation. In light of therapeutic benefits of herbal and synthetic cannabinoids, the vast potential of the endocannabinoid system for the treatment of gastrointestinal diseases has been demonstrated. This review focuses on the role of the endocannabinoid system in gut homeostasis and in the pathogenesis of intestinal disorders associated with intestinal motility, inflammation and cancer. Finally, links between gut microorganisms and the endocannabinoid system are briefly discussed.”
“The cannabinoid type two receptors (CB2), an important component of the endocannabinoid system, have recently emerged as neuromodulators and therapeutic targets for neurodegenerative diseases including Parkinson’s disease (PD).
The downregulation of CB2 receptors has been reported in the brains of PD patients. Therefore, both the activation and the upregulation of the CB2 receptors are believed to protect against the neurodegenerative changes in PD.
In the present study, we investigated the CB2 receptor-mediated neuroprotective effect of β-caryophyllene (BCP), a naturally occurring CB2 receptor agonist, in, a clinically relevant, rotenone (ROT)-induced animal model of PD.
Interestingly, BCP supplementation demonstrated the potent therapeutic effects against ROT-induced neurodegeneration, which was evidenced by BCP-mediated CB2 receptor activation and the fact that, prior administration of the CB2 receptor antagonist AM630 diminished the beneficial effects of BCP.
The present study suggests that BCP has the potential therapeutic efficacy to elicit significant neuroprotection by its anti-inflammatory and antioxidant activities mediated by activation of the CB2 receptors.”