Abstract Background Cannabis benefits patients with inflammatory bowel disease (IBD). Cannabinoid receptors are expressed in gut immune cells and in epithelial cells of inflamed guts. Mucosal healing (MH) requires epithelial layer restoration. Objective To analyze the effects of CB2 agonist on parameters implicated in gut inflammation and MH. Methods Mucosal samples from areas of inflamed/uninflamed colon from 16 patients with IBD were cultured without/with cannabinoid receptor 2 (CB2) agonist (JWH-133, 10 µM, 6 hours (hr)), and analyzed for epithelial/stromal cell proliferation, apoptosis (secretome matrix metalloproteinase 9 (MMP9) activity, which impairs epithelial permeability) and interleukin-8 (IL-8) levels (n = 5–9). In addition, Caco-2 (colon carcinoma epithelial cells) were...

Please use this link to access this publication. Abstract Prolonged status epilepticus (SE) in humans causes high mortality and brain inflammation–associated neuronal injury and morbidity in survivors. Currently, the only effective treatment is to terminate the seizures swiftly to prevent brain damage. However, reliance on acute therapies alone would be imprudent due to the required short response time. Follow-on therapies that can be delivered well after the SE onset are in an urgent need. Cannabinoid receptor type 2 (CB2), a G protein-coupled receptor that can be expressed by activated brain microglia, has emerged as an appealing anti-inflammatory target for brain conditions. In the current...

Please use this link to access this publication. Abstract Purpose Cannabinoids have been shown to exert analgesic and anti-inflammatory effects, and the effects of cannabinoids are mediated primarily by cannabinoid receptors 1 and 2 (CB1 and CB2). The objective of this study was to determine efficacy and mechanism of CB2 activation on cyclophosphamide (CYP)-induced cystitis in vivo. Methods Cystitis was induced by intraperitoneal (IP) injection of CYP in female C57BL/6J mice. Mice were pretreated with CB2 agonist JWH-133 (1 mg/kg, intraperitoneally), CB2 antagonist AM-630 (1 mg/kg, intraperitoneally) or autophagy inhibitor 3-methyladenine (3-MA) (50 mM, intraperitoneally) before IP injection of CYP. Peripheral nociception and spontaneous voiding were investigated...

Abstract Neuropathic pain conditions including neuropathic orofacial pain (NOP) are difficult to treat. Contemporary therapeutic agents for neuropathic pain are often ineffective in relieving pain and are associated with various adverse effects. Finding new options for treating neuropathic pain is a major priority in pain-related research. Cannabinoid-based therapeutic strategies have emerged as promising new options. Cannabinoids mainly act on cannabinoid 1 (CB1) and 2 (CB2) receptors, and the former is widely distributed in the brain. The therapeutic significance of cannabinoids is masked by their adverse effects including sedation, motor impairment, addiction and cognitive impairment, which are thought to be mediated by CB1 receptors in...

Please use this link to access this publication. Abstract HIV infection affects an estimated 38 million people. Approximately 50% of HIV patients exhibit neurocognitive dysfunction termed HIV-Associated Neurocognitive Disorder (HAND). HAND is a consequence of chronic low-level neuroinflammation due to HIV entry into the brain. Initially, monocytes become activated in circulation and traffic to the brain. Monocytes, when activated, become susceptible to infection by HIV and can then carry the virus across the blood brain barrier. Once in the brain, activated monocytes secrete chemokines, which recruit virus-specific CD8+ T cells into the brain to further promote neuroinflammation. HAND is closely linked to systemic inflammation driven,...

Abstract Cannabinoid CB2 receptor (CB2) agonists are potential analgesics void of psychotropic effects. Peripheral immune cells, neurons and glia express CB2; however, the involvement of CB2 from these cells in neuropathic pain remains unresolved. We explored spontaneous neuropathic pain through on-demand self-administration of the selective CB2 agonist JWH133 in wild-type and knockout mice lacking CB2 in neurons, monocytes or constitutively. Operant self-administration reflected drug-taking to alleviate spontaneous pain, nociceptive and affective manifestations. While constitutive deletion of CB2 disrupted JWH133-taking behavior, this behavior was not modified in monocyte-specific CB2 knockouts and was increased in mice defective in neuronal CB2 knockouts suggestive of increased spontaneous pain. Interestingly, CB2-positive lymphocytes infiltrated the injured nerve...

Abstract Background and Purpose Cannabis or cannabinoids produce characteristic tetrad effects—analgesia, hypothermia, catalepsy and suppressed locomotion, which are believed to be mediated by the activation of cannabinoid CB1 receptors. Given recent findings of CB2 and GPR55 receptors in the brain, we examined whether these receptors are also involved in cannabinoid action. Experimental Approach We compared Δ9-tetrahydrocannabinol (Δ9-THC)-, WIN55212-2-, or XLR11-induced tetrad effects between wild-type (WT) and each genotype of CB1-, CB2- or GPR55-knockout (KO) mice and then observed the effects of antagonists of these receptors on these tetrad effects in WT mice. Key Results Systemic administration of Δ9-THC, WIN55212-2 or XLR11 produced dose-dependent tetrad effects in...

Please use this link to access this publication. Abstract Study rationale Hepatorenal syndrome (HRS) is a life-threatening complication of end-stage liver disease characterized by the rapid decline of kidney function. Herein, we explored the therapeutic potential of targeting the cannabinoid-2 receptor (CB2-R) utilizing a commonly used mouse model of liver fibrosis and hepatorenal syndrome (HRS), induced by bile duct ligation (BDL). Methods Gene expression analysis, histological evaluation, determination of serum levels of renal injury-biomarkers were used to characterize the BDL-induced organ injury; laser speckle analysis to measure microcirculation in the kidneys. Key results We found that liver injury triggered marked inflammation and oxidative stress in the kidneys of BDL-operated mice. We detected pronounced histopathological alterations with tubular injury paralleled...

Please use this link to access this publication. Abstract Recently, there have been increasing indications that the endocannabinoid (eCB) system is involved in vision. Multiple research teams studied the cannabinoid receptor type 2 (CB2R) expression and function in the mouse retina. Here, we examined the consequence of CB2R modulation on visual acuity using genetic and pharmacologic tools. We found that Cnr2 knockout mice show an enhanced visual acuity, CB2R activation decreased visual acuity while CB2R blockade with the inverse agonist AM630 increased it. The inhibition of 2-arachidonylglycerol (2-AG) synthesis and degradation also greatly increased and decreased visual acuity, respectively. No differences were seen when the cannabinoid...

Please use this link to access this publication. Abstract Background Recent approved medicines whose active principles are Δ9Tetrahidrocannabinol (Δ9-THC) and/or cannabidiol (CBD) open novel perspectives for other phytocannabinoids also present in Cannabis sativa L. varieties. Furthermore, solid data on the potential benefits of acidic and varinic phytocannabinoids in a variety of diseases are already available. Mode of action of cannabigerol (CBG), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), cannabidivarin (CBDV) and cannabigerivarin (CBGV) is, to the very least, partial. Hypothesis/Purpose Cannabinoid CB1 or CB2 receptors, which belong to the G-protein-coupled receptor (GPCR) family, are important mediators of the action of those cannabinoids. Pure CBG, CBDA, CBGA, CBDV and CBGV from Cannabis sativa L. are differentially acting on CB1 or CB2 cannabinoid...