Tag Archives: anti-inflammatory

Cannabidiol protects livers against nonalcoholic steatohepatitis induced by high-fat high cholesterol diet via regulating NF-κB and NLRP3 inflammasome pathway.

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“Cannabidiol (CBD), an abundant nonpsychoactive constituent of marijuana, has been reported previously to protect against hepatic steatosis.

In this study, we studied further the functions and mechanisms of CBD on liver inflammation induced by HFC diet.

Mice feeding an HFC diet for 8 weeks were applied to test the protective effect of CBD on livers. RAW264.7 cells were incubated with LPS + ATP ± CBD to study the mechanisms of the effect of CBD against inflammasome activation.

We found that CBD alleviated liver inflammation induced by HFC diet.

CBD significantly inhibited the nuclear factor-κappa B (NF-κB) p65 nuclear translocation and the activation of nucleotide-binding domain like receptor protein 3 (NLRP3) inflammasome both in vivo and in vitro studies, which lead to the reduction of the expression of inflammation-related factors in our studies.

In addition, Inhibitor of activation of NF-κB partly suppressed the NLRP3 inflammasome activation, while adding CBD further inhibited NF-κB activation and correspondingly suppressed the NLRP3 inflammasome activation in macrophages.

In conclusion, the suppression of the activation of NLRP3 inflammasome through deactivation of NF-κB in macrophages by CBD might be one mechanism of its anti-inflammatory function in the liver.”

https://www.ncbi.nlm.nih.gov/pubmed/31032942

https://onlinelibrary.wiley.com/doi/abs/10.1002/jcp.28728

A Novel Standardized Cannabis sativa L. Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functions.

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“Cannabis and cannabinoids offer significant therapeutic benefits for a wide scope of pathological conditions. Among them, the clinical issues rooted in inflammation stand out, nonetheless, the underlying mechanisms are not yet plainly understood. Circumstantial evidence points to polymorphonuclear leukocytes (PMN) as targets for the anti-inflammatory effects of cannabis. Therefore, we conducted this study to assess the effects of CM5, a novel Cannabis sativa L. extract standardized in 5% cannabidiol (CBD), on human PMN functions, including cell migration, oxidative metabolism and production of tumour necrosis factor (TNF)-α. We then sought to investigate whether such effects could be ascribed to its content in CBD. Cell migration was assessed by the Boyden chamber assay, oxidative metabolism by means of spectrofluorimetric measurement of reactive oxygen species (ROS) production, and TNF-α was measured by real time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Results show that both CM5 and CBD inhibit PMN migration, ROS and TNF-α production, indicating that CBD may be the main item responsible for the effects of CM5. CM5 is however more potent than CBD on cell migration and TNF-α production, and less effective on ROS production, suggesting that beyond CBD, other components of the cannabis plant may contribute to the biological effects of the extract. As a whole, such results support the use of cannabis standardized extract and CBD to stem inflammation; however, they also warrant in-depth investigation of the underlying cellular and molecular mechanisms to better exploit their therapeutic potential.”

https://www.ncbi.nlm.nih.gov/pubmed/31013912

https://www.mdpi.com/1422-0067/20/8/1833

Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials.

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“Cannabidiol (CBD) is one of the cannabinoids with non-psychotropic action, extracted from Cannabis sativa. CBD is a terpenophenol and it has received a great scientific interest thanks to its medical applications. This compound showed efficacy as anti-seizure, antipsychotic, neuroprotective, antidepressant and anxiolytic. The neuroprotective activity appears linked to its excellent anti-inflammatory and antioxidant properties. The purpose of this paper is to evaluate the use of CBD, in addition to common anti-epileptic drugs, in the severe treatment-resistant epilepsy through an overview of recent literature and clinical trials aimed to study the effects of the CBD treatment in different forms of epilepsy. The results of scientific studies obtained so far the use of CBD in clinical applications could represent hope for patients who are resistant to all conventional anti-epileptic drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/31013866

https://www.mdpi.com/1420-3049/24/8/1459

Potential for endocannabinoid system modulation in ocular pain and inflammation: filling the gaps in current pharmacological options

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Neuronal Signaling

“Challenges in the management of ocular pain are an underappreciated topic. Currently available therapeutics lack both efficacy and clear guidelines for their use, with many also possessing unacceptable side effects. Promising novel agents would offer analgesic, anti-inflammatory, and possibly neuroprotective actions; have favorable ocular safety profiles; and show potential in managing neuropathic pain.

Growing evidence supports a link between the endocannabinoid system (ECS) and a range of physiological and disease processes, notably those involving inflammation and pain. Both preclinical and clinical data suggest analgesic and anti-inflammatory actions of cannabinoids and ECS-modifying drugs in chronic pain conditions, including those of neuropathic origin.

The ECS is present ubiquitously through the body, including a range of ocular tissues, and represents a promising target in the treatment of several physiological and pathophysiologic processes in the eye including, but not limited to, pain, inflammation, and neuronal damage. ”

http://www.neuronalsignaling.org/content/2/4/NS20170144

AM-1241 CB2 Receptor Agonist Attenuates Inflammation, Apoptosis and Stimulate Progenitor Cells in Bile Duct Ligated Rats.

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 “The cannabinoid receptor 2 (CB2) plays a pleiotropic role in the innate immunity and is considered a crucial mediator of liver disease.

Cannabinoid CB2 receptor activation has been reported to attenuate liver fibrosis in CCl4 exposed mice and also plays a potential role in liver regeneration in a mouse model of I/R and protection against alcohol-induced liver injury.

AIM:

In this study, we investigated the impact of CB2 receptors on the antifibrotic and regenerative process associated with cholestatic liver injury.

RESULTS:

Following bile duct ligation (BDL) for 3 weeks, there was increased aminotransferase levels, marked inflammatory infiltration and hepatocyte apoptosis with induced oxidative stress, as reflected by increased lipid peroxidation. Conversely, following treatment with the CB2 agonist, AM-1241, BDL rats displayed a reduction in liver injury and attenuation of fibrosis as reflected by expression of hydroxyproline and α-smooth muscle actin. AM1241 treatment also significantly attenuated lipid peroxidation end-products, p53-dependent apoptosis and also attenuated inflammatory process by stimulating IL-10 production. Moreover, AM1241 treated rats were associated with significant expression of hepatic progenitor/oval cell markers.

CONCLUSION:

In conclusion, this study points out that CB2 receptors reduce liver injury and promote liver regeneration via distinct mechanisms including IL-10 dependent inhibition of inflammation, reduction of p53-reliant apoptosis and through stimulation of oval/progenitor cells. These results suggest that CB2 agonists display potent hepatoregenrative properties, in addition to their antifibrogenic effects.”

https://www.ncbi.nlm.nih.gov/pubmed/30976335

https://www.id-press.eu/mjms/article/view/oamjms.2019.194

Joints for joints: cannabinoids in the treatment of rheumatoid arthritis.

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“An increasing number of patients with rheumatoid arthritis (RA) are using cannabis to treat their symptoms, although systematic studies regarding efficacy in RA are lacking. Within this review we will give an overview on the overall effects of cannabinoids in inflammation and why they might be useful in the treatment of RA.

RECENT FINDINGS:

Peripherally, cannabinoids show anti-inflammatory effects by activating cannabinoid type 2 receptors (CB2) which decrease cytokine production and immune cell mobilization. In contrast, cannabinoid type 1 receptor (CB1) activation on immune cells is proinflammatory while CB1 antagonism provides anti-inflammatory effects by increasing β2-adrenergic signaling in the joint and secondary lymphoid organs. In addition, the nonpsychotropic cannabinoid, cannabidiol (CBD) demonstrated antiarthritic effects independent of cannabinoid receptors. In addition to controlling inflammation, cannabinoids reduce pain by activating central and peripheral CB1, peripheral CB2 receptors and CBD-sensitive noncannabinoid receptor targets.

SUMMARY:

Cannabinoids might be a suitable treatment for RA, but it is important to target the right receptors in the right place. For clinical studies, we propose a combination of a CB2 agonist to decrease cytokine production, a peripheral CB1 antagonist to prevent detrimental CB1 signaling and to support anti-inflammatory effects of CB2 via activation of β2-adrenergic receptors and CBD to induce cannabinoid-receptor-independent anti-inflammatory effects.”

 https://www.ncbi.nlm.nih.gov/pubmed/30920973
https://insights.ovid.com/crossref?an=00002281-201905000-00009

Investigating the Relationships Between Alcohol Consumption, Cannabis Use, and Circulating Cytokines: A Preliminary Analysis.

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Alcoholism: Clinical and Experimental Research banner

“In recent years, human and animal studies have converged to support altered inflammatory signaling as a molecular mechanism underlying the pathophysiology of alcohol use disorders (AUDs). Alcohol binds to receptors on immune cells, triggering signaling pathways that produce pro-inflammatory cytokines. Chronic inflammation is associated with tissue damage, which may contribute to negative effects of AUD. Conversely, cannabis is associated with decreased inflammatory signaling, and animal studies suggest that cannabinoids may impact alcohol-induced inflammation. Thus, the impact of cannabis on inflammation in AUDs in humans warrants examination.

METHODS:

We explored the relationship between self-reported alcohol and cannabis use and circulating levels of the pro-inflammatory cytokines interleukin 6 (IL-6), IL-8, and IL-1β in the blood. Among 66 regular drinkers (mean age = 30.08), we examined circulating cytokines and administered questionnaires assessing alcohol consumption and days of cannabis use over the past 90 days. We examined whether alcohol consumption, cannabis use, and gender were associated with changes in circulating cytokines, and whether there was a significant interaction between alcohol and cannabis use predicting blood levels of circulating cytokines.

RESULTS:

A positive association between alcohol and IL-6 emerged. We also observed a negative association between cannabis and IL-1β. Follow-up moderation analyses indicated a cannabis by alcohol interaction predicting circulating IL-6, such that cannabis nonusers showed a stronger relationship between alcohol and IL-6 compared to cannabis users.

CONCLUSIONS:

These preliminary findings suggest that cannabinoid compounds may serve to mitigate inflammation associated with alcohol use. In addition, the present results provide data to inform future investigations, with the goal of ultimately leveraging knowledge of the role of inflammation in AUDs to develop more effective treatments focused on novel immune targets.”

https://www.ncbi.nlm.nih.gov/pubmed/29286537

https://onlinelibrary.wiley.com/doi/abs/10.1111/acer.13592

GPR55 – a putative “type 3” cannabinoid receptor in inflammation.

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“G protein-coupled receptor 55 (GPR55) shares numerous cannabinoid ligands with CB1 and CB2 receptors despite low homology with those classical cannabinoid receptors. The pharmacology of GPR55 is not yet fully elucidated; however, GPR55 utilizes a different signaling system and downstream cascade associated with the receptor. Therefore, GPR55 has emerged as a putative “type 3″ cannabinoid receptor, establishing a novel class of cannabinoid receptor. Furthermore, the recent evidence of GPR55-CB1 and GPR55-CB2 heteromerization along with its broad distribution from central nervous system to peripheries suggests the importance of GPR55 in various cellular processes and pathologies and as a potential therapeutic target in inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/26669245

https://www.degruyter.com/view/j/jbcpp.2016.27.issue-3/jbcpp-2015-0080/jbcpp-2015-0080.xml

Cannabimimetic plants: are they new cannabinoidergic modulators?

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“Phytochemicals and secondary metabolites able to interact with the endocannabinoid system (Cannabimimetics) have been recently described in a broad range of plants and fruits. These findings can open new alternative avenues to explore for the development of novel therapeutic compounds. The cannabinoids regulate many physiological and pathological functions in both animals and plants. Cannabis sativa is the main plant that produces phytocannabinoids inside resins capable to defend the plant from the aggression of parasites and herbivores. Animals produce anandamide and 2-arachidonoyl glycerol, which thanks to binding with main receptors such as type-1 cannabinoid receptor (CB1R) and the type-2 cannabinoid receptor (CB2R) are involved in inflammation processes and several brain functions. Endogenous cannabinoids, enzymes for synthesis and degradation of cannabinoids, and CB1R and CB2R constitute the endocannabinoid system (ECS). Other plants can produce cannabinoid-like molecules such as perrottetinene extracted from Radula perrottetii, or anandamide and 2-arachidonoyl glycerol extracted from some bryophytes. Moreover, several other secondary metabolites can also interact with the ECS of animals and take the name of cannabimimetics. These phytoextracts not derived from Cannabis sativa can act as receptor agonists or antagonist, or enzyme inhibitors of ECS and can be involved in the inflammation, oxidative stress, cancer, and neuroprotection. Finally, given the evolutionary heterogeneity of the cannabimimetic plants, some authors speculated on the fascinating thesis of the evolutionary convergence between plants and animals regarding biological functions of ECS. The review aims to provide a critical and complete assessment of the botanical, chemical and therapeutic aspects of cannabimimetic plants to evaluate their spread in the world and medicinal potentiality.”

https://www.ncbi.nlm.nih.gov/pubmed/30877436

https://link.springer.com/article/10.1007%2Fs00425-019-03138-x

Members of the endocannabinoid system are distinctly regulated in inflammatory bowel disease and colorectal cancer.

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Scientific Reports

“Preclinical studies have demonstrated that the endocannabinoid system (ECS) plays an important role in the protection against intestinal inflammation and colorectal cancer (CRC); however, human data are scarce. We determined members of the ECS and related components of the ‘endocannabinoidome’ in patients with inflammatory bowel disease (IBD) and CRC, and compared them to control subjects. Anandamide (AEA) and oleoylethanolamide (OEA) were increased in plasma of ulcerative colitis (UC) and Crohn’s disease (CD) patients while 2-arachidonoylglycerol (2-AG) was elevated in patients with CD, but not UC. 2-AG, but not AEA, PEA and OEA, was elevated in CRC patients. Lysophosphatidylinositol (LPI) 18:0 showed higher levels in patients with IBD than in control subjects whereas LPI 20:4 was elevated in both CRC and IBD. Gene expression in intestinal mucosal biopsies revealed different profiles in CD and UC. CD, but not UC patients, showed increased gene expression for the 2-AG synthesizing enzyme diacylglycerol lipase alpha. Transcripts of CNR1 and GPR119 were predominantly decreased in CD. Our data show altered plasma levels of endocannabinoids and endocannabinoid-like lipids in IBD and CRC and distinct transcript profiles in UC and CD. We also report alterations for less known components in intestinal inflammation, such as GPR119, OEA and LPI.”

 https://www.ncbi.nlm.nih.gov/pubmed/30787385
https://www.nature.com/articles/s41598-019-38865-4