Category Archives: Endocannabinoid System

Investigation of the Involvement of the Endocannabinoid System in TENS-induced Antinociception.

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“Transcutaneous electrical nerve stimulation (TENS) promotes antinociception by activating the descending pain modulation pathway and consequently releasing endogenous analgesic substances.

In addition, recent studies have shown that the endocannabinoid system controls pain. Thus, the present study investigated the involvement of the endocannabinoid system in TENS-induced antinociception of cancer pain using a cancer pain model induced by intraplantar (i.pl.) injections of Ehrlich tumor cells in male Swiss mice.

These results suggest that low- and high-frequency TENS is effective in controlling cancer pain, and the endocannabinoid system is involved in this effect at both the peripheral and central levels.

Perspective: TENS is a non-pharmacological strategy that may be used to control cancer pain. Identification of a new mechanism involved in its analgesic effect could lead to the development of clinical studies as well as an increase in its application, lessening the need for pharmacological treatments.”

https://www.ncbi.nlm.nih.gov/pubmed/31785404

https://www.jpain.org/article/S1526-5900(19)30868-5/fulltext

Influence of the CB1 and CB2 cannabinoid receptor ligands on the activity of atypical antidepressant drugs in the behavioural tests in mice.

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Pharmacology Biochemistry and Behavior“Available data support the notion that cannabinoids, whose therapeutic value is limited due to severe adverse reactions, could be beneficial as adjunctive agents in the management of mood disorders.

Polytherapy, which is superior to monotherapy in the terms of effectiveness, usually requires lower doses of the individual components. Therefore, the main objective of our study was to determine whether administration of cannabinoid (CB) receptor ligands would enhance the antidepressant activity of atypical antidepressant drugs, i.e. agomelatine and tianeptine.

In summary, the outcomes of the present study showed that activation and inhibition of CB1 receptors as well as inhibition of CB2 receptors may increase the antidepressant activity of tianeptine, whereas only inhibition of CB1 and CB2 receptors has a potential to augment the antidepressant activity of agomelatine.”

https://www.ncbi.nlm.nih.gov/pubmed/31785246

https://www.sciencedirect.com/science/article/pii/S0091305719304873?via%3Dihub

The Endocannabinoid System in Pediatric Inflammatory and Immune Diseases.

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 ijms-logo“Endocannabinoid system consists of cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptors, their endogenous ligands, and the enzymes responsible for their synthesis and degradation. CB2, to a great extent, and CB1, to a lesser extent, are involved in regulating the immune response. They also regulate the inflammatory processes by inhibiting pro-inflammatory mediator release and immune cell proliferation. This review provides an overview on the role of the endocannabinoid system with a major focus on cannabinoid receptors in the pathogenesis and onset of inflammatory and autoimmune pediatric diseases, such as immune thrombocytopenia, juvenile idiopathic arthritis, inflammatory bowel disease, celiac disease, obesity, neuroinflammatory diseases, and type 1 diabetes mellitus. These disorders have a high social impact and represent a burden for the healthcare system, hence the importance of individuating more innovative and effective treatments. The endocannabinoid system could address this need, representing a possible new diagnostic marker and therapeutic target.”

https://www.ncbi.nlm.nih.gov/pubmed/31771129

https://www.mdpi.com/1422-0067/20/23/5875

The curative effect of a cannabinoid 2 receptor agonist on functional failure and disruptive inflammation caused by intestinal ischemia and reperfusion.

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Publication cover image“As we learn more about the endocannabinoid system (ECS), our understanding and grasp of the system’s ubiquitous presence is expanding. In light of this, there is also a growing body of evidence for the therapeutic potential of ECS modulation in a range of clinical situations. Strategies include for example manipulation of the Cannabinoid 1 (CB1) receptor, mostly in terms of CNS processes, and activation of the Cannabinoid 2 (CB2) receptor as anti-inflammatory target.”

https://www.ncbi.nlm.nih.gov/pubmed/31774568

https://onlinelibrary.wiley.com/doi/abs/10.1111/fcp.12524

Alcohol Binge-Induced Cardiovascular Dysfunction Involves Endocannabinoid-CB1-R Signaling.

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 JACC: Basic to Translational Science“Excessive binge alcohol drinking may adversely affect cardiovascular function. In this study we characterize the detailed hemodynamic effects of an acute alcohol binge in mice using multiple approaches and investigate the role of the endocannabinoid-cannabinoid 1 receptor (CB1-R) signaling in these effects. Acute alcohol binge was associated with elevated levels of cardiac endocannabinoid anandamide and profound cardiovascular dysfunction lasting for several hours and redistribution of circulation. These changes were attenuated by CB1-R antagonist or in CB1-R knockout mice. Our results suggest that a single alcohol binge has profound effects on the cardiovascular system, which involve endocannabinoid-CB1-R signaling.”

https://www.ncbi.nlm.nih.gov/pubmed/31768478

“Alcohol is one of the most frequently used intoxicants in the United States. Binge alcohol drinking is a major contributor of emergency department visits. Binge alcohol drinking may adversely affect cardiovascular function. Here we show that acute alcohol intoxication is associated with elevated levels of cardiac endocannabinoid anandamide and profound cardiovascular dysfunction and blood redistribution lasting for several hours. The adverse cardiovascular effects of acute alcohol intoxication are attenuated by CB1-R antagonist or in CB1-R knockout mice. A single alcohol binge has profound effect on the cardiovascular system, which involves endocannabinoid-CB1-R signaling.”

https://www.sciencedirect.com/science/article/pii/S2452302X19301755?via%3Dihub

Cannabinoid-2 receptor activation ameliorates hepatorenal syndrome.

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Free Radical Biology and Medicine“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).

KEY RESULTS:

We found that liver injury triggered marked inflammation and oxidative stress also in the kidneys of BDL-operated mice. We detected pronounced histopathological alterations with tubular injury paralleled with increased inflammation, oxidative/nitrative stress and fibrotic remodeling both in hepatic and renal tissues as well as endothelial activation and markedly impaired renal microcirculation. This was accompanied by increased CB2-R expression in both liver and the kidney tissues of diseased animals. A selective CB2-R agonist, HU-910, markedly decreased numerous markers of inflammation, oxidative stress and fibrosis both in the liver and in the kidneys. HU-910 also attenuated markers of kidney injury and improved the impaired renal microcirculation in BDL-operated mice.

CONCLUSIONS:

Our results suggest that oxidative stress, inflammation and microvascular dysfunction are key events in the pathogenesis of BDL-associated renal failure. Furthermore, we demonstrate that targeting the CB2-R by selective agonists may represent a promising new avenue to treat HRS by attenuating tissue and vascular inflammation, oxidative stress, fibrosis and consequent microcirculatory dysfunction in the kidneys.”

https://www.ncbi.nlm.nih.gov/pubmed/31770583

“Bile duct ligation (BDL) causes hepatorenal syndrome (HRS). Oxidative damage/inflammation drives liver and kidney injury following BDL. Cannabinoid-2 receptor (CB2-R) activation attenuates hepatic damage in BDL. CB2-R activation mitigates the renal inflammation and oxidative damage in BDL. CB2-R activation attenuates renal microcirculatory dysfunction in BDL.”

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The ameliorating effect of cannabinoid type 2 receptor activation on brain, lung, liver and heart damage in cecal ligation and puncture-induced sepsis model in rats.

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International Immunopharmacology“Uncontrolled infection and increased inflammatory mediators might cause systemic inflammatory response. It is already known that Cannabinoid Type 2 (CB2) receptors, which are commonly expressed in immune cells and in many other tissues, have an effect on the regulation of immune response.

In the present study of ours, the effects of CB2 receptor agonist JWH-133 was investigated on cecal ligation and puncture (CLP)-induced polymicrobial sepsis model in rats.

The JWH-133 treatment decreased the histopathological damage in brain, heart, lung, and liver and reduced the caspase-3, p-NF-κB, TNF-α, IL-1β, IL-6 levels in these tissues. In addition to this, JWH-133 treatment also decreased the serum TNF-α, IL-1β, IL-6 levels, which were increased due to CLP, and increased the anti-inflammatory cytokine IL-10 levels.

In the present study, it was determined that the CB2 receptor agonist JWH-133 decreases the CLP-induced inflammation, and reduces the damage in brain, lung, liver and heart.

Our findings show the therapeutic potential of the activation of CB2 receptors with JWH-133 in sepsis.”

https://www.ncbi.nlm.nih.gov/pubmed/31767546

“CB2 receptors are expressed in many tissues including immune cells. Activation of CB2 receptors has been shown to have anti-inflammatory effect.”

https://www.sciencedirect.com/science/article/pii/S1567576919318351?via%3Dihub

Experimental Cannabinoid 2 Receptor Activation by Phyto-Derived and Synthetic Cannabinoid Ligands in LPS-Induced Interstitial Cystitis in Mice.

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molecules-logo“Interstitial cystitis (IC) is a chronic bladder disorder with unclear etiology.

The endocannabinoid system has been identified as a key regulator of immune function, with experimental evidence for the involvement of cannabinoid receptors in bladder inflammation.

This study used intravital microscopy (IVM) and behavioral testing in lipopolysaccharide-induced IC, to investigate the anti-inflammatory analgesic effects of a natural dietary sesquiterpenoid, beta-caryophyllene (BCP), which is present in cannabis among other plants, and has reported agonist actions at the cannabinoid 2 receptor (CB2R).

BCP’s anti-inflammatory actions were compared to the synthetic CB2R-selective cannabinoid, HU308, and to an FDA-approved clinical treatment (dimethyl sulfoxide: DMSO). IVM data revealed that intravesical instillation of BCP and/or HU308 significantly reduces the number of adhering leukocytes in submucosal bladder venules and improves bladder capillary perfusion.

The effects of BCP were found to be comparable to that of the selective CB2R synthetic cannabinoid, HU308, and superior to intravesical DMSO treatment. Oral treatment with BCP was also able to reduce bladder inflammation and significantly reduced mechanical allodynia in experimental IC.

Based on our findings, we believe that CB2R activation may represent a viable therapeutic target for IC, and that drugs that activate CB2R, such as the generally regarded as safe (GRAS) dietary sesquiterpenoid, BCP, may serve as an adjunct and/or alternative treatment option for alleviating symptoms of inflammation and pain in the management of IC.”

https://www.ncbi.nlm.nih.gov/pubmed/31766439

https://www.mdpi.com/1420-3049/24/23/4239

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142

Reduced cannabinoid 2 receptor activity increases susceptibility to induced seizures in mice.

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Publication cover image“The endocannabinoid system (ECS) is comprised of cannabinoid receptors 1 and 2 (CB1R and CB2R), endogenous ligands, and regulatory enzymes, and serves to regulate several important physiological functions throughout the brain and body.

Recent evidence suggests that the ECS may be a promising target for the treatment of epilepsy, including epilepsy subtypes that arise from mutations in the voltage-gated sodium channel SCN1A.

The objective of this study was to explore the effects of modulating CB2R activity on seizure susceptibility.

Our results demonstrate that reduced CB2R activity is associated with increased seizure susceptibility. CB2Rs might therefore provide a therapeutic target for the treatment of some forms of epilepsy.”

https://www.ncbi.nlm.nih.gov/pubmed/31758544

https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.16388

Association between cannabis and the eyelids: A comprehensive review.

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Publication cover image“Cannabis is the most consumed illicit drug worldwide. As more countries consider bills that would legalize adult use of cannabis, health care providers, including eye care professionals (ophthalmologists, optometrists), will need to recognize ocular effects of cannabis consumption in patients.

There are only 20 studies on the eyelid effects of cannabis usage as a medical treatment or a recreational drug.

These include: ptosis induction, an “eyelid tremor” appearance and blepharospasm attenuation.

Six articles describe how adequately dosed cannabis regimens could be promising medical treatments for blepharospasm induced by psychogenic factors.

The exact mechanism of cannabinoids connecting cannabis to the eyelids is unclear.

Further studies should be conducted to better understand the cannabinoid system in relation to the eyelid and eventually develop new, effective and safe therapeutic targets derived from cannabis.”

https://www.ncbi.nlm.nih.gov/pubmed/31747112

https://onlinelibrary.wiley.com/doi/abs/10.1111/ceo.13687