Monthly Archives: June 2019

A selective CB2 agonist protects against the inflammatory response and joint destruction in collagen-induced arthritis mice.

Posted on by
Reply

Biomedicine & Pharmacotherapy

“Rheumatoid arthritis (RA) is a chronic, inflammatory, synovitis-dominated systemic disease with unknown etiology. RA is characterized by the involvement of multiple affected joints, symmetry, and invasive arthritis of the limbs, which can lead to joint deformity, cartilage destruction, and loss of function. Cannabinoid receptor 2 (CB2) has potent immunomodulatory and anti-inflammatory effects and is predominantly expressed in non-neuronal tissues. In the current study, the role of CB2 in the process of inflammatory bone erosion in RA was examined. The selective agonist or high-affinity ligand of CB2 (4-quinolone-3-carboxamides CB2 agonist, 4Q3C CB2agonist, 4Q3C) significantly reduced the severity of arthritis, decreased histopathological findings, and markedly reduced bone erosion in collagen-induced arthritis (CIA) mice. In addition, 4Q3C prevented an increase in the nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) ratio and inhibited the formation of osteoclasts in CIA mice. Furthermore, the expression of tumor necrosis factor-alpha, interleukin-1β, cyclooxygenase-2, and inducible nitric oxide synthase was lower in 4Q3C-treated CIA mice than in control CIA mice. Micro-computed tomography corroborated the finding that 4Q3C reduced joint destruction. These data clearly indicate that the CB2-selective agonist, 4Q3C, may have anti-inflammatory and anti-osteoclastogenesis effects in RA and may be considered to be a novel treatment for RA.”

https://www.ncbi.nlm.nih.gov/pubmed/31154267

https://www.sciencedirect.com/science/article/pii/S0753332219307528?via%3Dihub

CB2 Cannabinoid receptor agonist ameliorates novel object recognition but not spatial memory in transgenic APP/PS1 mice.

Posted on by
Reply

Neuroscience Letters

“The cannabinoid receptor 2 (CB2R) has been considered as a potential therapeutic target to ameliorate the neuroinflammation and cognitive impairments of Alzheimer’s disease (AD). However, there has been little research on the diverse roles of CB2R in regulating different forms of cognitive abilities and underlying neuroinflammatory mechanisms. Thus, the focus of the present study was to investigate the effects of CB2R activation on cognitive abilities, activation and phenotype conversion of microglia, and dendrite complexity.

Results showed that CB2R activation normalized the cortex-dependent novel object recognition memory deficit in a novel object recognition test (P < 0.05) and CB2R activation was ineffective for hippocampus-dependent spatial cognitive dysfunction in the Morris water maze test (P > 0.05). Moreover, activation of CB2R did not affect the formation of plaque in either the cortex or hippocampus (P > 0.05). Interestingly, in the cortex but not in the hippocampus of APP/PS1 mice, there was decreased immunofluorescence intensity of Iba1, M1 to M2 microglial phenotype conversion, and restored dendritic complexity after a long treatment period of CB2R agonist (All P < 0.05).

Our results demonstrated that CB2R activation exerts a beneficial role in novel object recognition ability concomitant with region-specific regulation in microglia-mediated neuroinflammation and dendritic complexity in AD-model mice.”

https://www.ncbi.nlm.nih.gov/pubmed/31150731

https://www.sciencedirect.com/science/article/pii/S0304394019303581?via%3Dihub

The Endocannabinoid System: A New Treatment Target for Obsessive Compulsive Disorder?

Posted on by
Reply

View details for Cannabis and Cannabinoid Research cover image

“Obsessive-compulsive disorder (OCD) is a disabling illness that is associated with significant functional impairment. Although evidence-based pharmacotherapies exist, currently available medications are ineffective in some patients and may cause intolerable side effects in others. There is an urgent need for new treatments.

Discussion: A growing body of basic and clinical research has showed that the endocannabinoid system (ECS) plays a role in anxiety, fear, and repetitive behaviors. At the same time, some patients with OCD who smoke cannabis anecdotally report that it relieves their symptoms and mitigates anxiety, and several case reports describe patients whose OCD symptoms improved after they were treated with cannabinoids. Taken together, these findings suggest that the ECS could be a potential target for novel medications for OCD. In this study, we review evidence from both animal and human studies that suggests that the ECS may play a role in OCD and related disorders. We also describe findings from studies in which cannabinoid drugs were shown to impact symptoms of these conditions.

Recent studies in both humans and animals have shown a critical role for the ECS in anxiety, stress, fear, and repetitive/habitual behaviors. Moreover, many patients with OCD who use cannabis anecdotally report that it improves their symptoms and reduces anxiety.

Conclusions: An emerging body of evidence suggests that the ECS plays a role in OCD symptoms and may be a target for the development of novel medications. Further exploration of this topic through well-designed human trials is warranted.”

https://www.liebertpub.com/doi/10.1089/can.2018.0049

“Can cannabinoids help treat obsessive-compulsive disorder?”  https://eurekalert.org/pub_releases/2019-05/mali-cch053119.php

Modulation of the Endocannabinoid System as a Potential Anticancer Strategy.

Posted on by
Reply

 Image result for frontiers in pharmacology“Currently, the involvement of the endocannabinoid system in cancer development and possible options for a cancer-regressive effect of cannabinoids are controversially discussed. In recent decades, a number of preclinical studies have shown that cannabinoids have an anticarcinogenic potential. Therefore, especially against the background of several legal simplifications with regard to the clinical application of cannabinoid-based drugs, an extended basic knowledge about the complex network of the individual components of the endocannabinoid system is required. The canonical endocannabinoid system consists of the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol as well as the Gi/o protein-coupled transmembrane cannabinoidreceptors CB1 and CB2. As a result of extensive studies on the broader effect of these factors, other fatty acid derivatives, transmembrane and intracellular receptors, enzymes and lipid transporters have been identified that contribute to the effect of endocannabinoids when defined in the broad sense as “extended endocannabinoid system.” Among these additional components, the endocannabinoid-degrading enzymes fatty acid amide hydrolase and monoacylglycerol lipase, lipid transport proteins of the fatty acid-binding protein family, additional cannabinoid-activated G protein-coupled receptors such as GPR55, members of the transient receptor family, and peroxisome proliferator-activated receptors were identified as targets for possible strategies to combat cancer progression. Other endocannabinoid-related fatty acids such as 2-arachidonoyl glyceryl ether, O-arachidonoylethanolamine, N-arachidonoyldopamine and oleic acid amide showed an effect via cannabinoid receptors, while other compounds such as endocannabinoid-like substances exert a permissive action on endocannabinoid effects and act via alternative intracellular target structures. This review gives an overview of the modulation of the extended endocannabinoid system using the example of anticancer cannabinoid effects, which have been described in detail in preclinical studies.”

https://www.ncbi.nlm.nih.gov/pubmed/31143113

“In addition to the palliative effects of cannabinoid compounds in cancer treatment, the endocannabinoid system provides several targets for systemic anticancer treatment. Accordingly, preclinical studies suggest cannabinoids inhibit cancer progression via inhibition of cancer cell proliferation, neovascularization, invasion and chemoresistance, as well as induction of apoptosis, autophagy and increase of tumor immune surveillance.”

https://www.frontiersin.org/articles/10.3389/fphar.2019.00430/full