Category Archives: Pancreatitis

Cannabidiol Mitigates Lipopolysaccharide-Induced Pancreatic Pathology: A Promising Therapeutic Strategy

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“Background: Lipopolysaccharides (LPSs) are a component of certain types of bacteria and can induce an inflammatory response in the body, including in the pancreas. Cannabidiol (CBD), a nonpsychoactive compound found in cannabis, has been shown to have anti-inflammatory effects and may offer potential therapeutic benefits for conditions involving inflammation and damage. The aim of this study was to investigate any potential preventative effects of CBD on experimental LPS-induced pancreatic pathology in rats. 

Materials and Methods: Thirty-two rats were randomly divided into four groups as control, LPS (5 mg/kg, intraperitoneally [i.p.]), LPS+CBD, and CBD (5 mg/kg, i.p.) groups. Six hours after administering LPS, the rats were euthanized, and blood and pancreatic tissue samples were taken for biochemical, polymerase chain reaction (PCR), histopathological, and immunohistochemical examinations. 

Results: The results indicated that LPS decreased serum glucose levels and increased lipase levels. It also caused severe hyperemia, increased vacuolization in endocrine cells, edema, and slight inflammatory cell infiltrations at the histopathological examination. Insulin and amylin expressions decreased during immunohistochemical analyses. At the PCR analysis, Silent Information Regulator 2 homolog 1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha expressions decreased and tumor protein p53 expressions increased in the LPS group. CBD improved the biochemical, PCR, histopathological, and immunohistochemical results. 

Conclusions: The findings of the current investigation demonstrated that LPS damages both the endocrine and exocrine pancreas. However, CBD demonstrated marked ameliorative effects in the pancreas in LPS induced rat model pancreatitis.”

https://pubmed.ncbi.nlm.nih.gov/37903028/

https://www.liebertpub.com/doi/10.1089/can.2023.0153

The Impact of Cannabis Consumption on Mortality, Morbidity, and Cost in Acute Pancreatitis Patients in the United States: A 10-Year Analysis of the National Inpatient Sample.

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“The aim of this study was to identify the prevalence of cannabis use among all patients admitted with acute pancreatitis (AP) in the United States and to investigate the impact of cannabis use on AP mortality, morbidity, and cost of care.

RESULTS:

More than 2.8 million patients with AP patients were analyzed. Cannabis-exposed (CE) patients’ prevalence was 0.3%. Patients exposed to cannabis were younger and mostly males compared with non-cannabis-exposed patients. After adjusting for these factors, the CE group had significantly lower inpatient mortality compared with the noncannabis group (odds ratio, 0.17; 95% confidence interval, 0.06-0.53). Cannabis-exposed patients also had decreased length of stay, inflation-adjusted charges, acute kidney injury, ileus, shock, acute respiratory distress syndrome, and parenteral nutrition requirement.

CONCLUSIONS:

Cannabis-exposed hospitalized patients with AP had lower age-adjusted, mortality, morbidity, and hospitalization-cost than non-cannabis-exposed patients.”

 https://www.ncbi.nlm.nih.gov/pubmed/31210668
https://insights.ovid.com/crossref?an=00006676-201907000-00017

Reduced Risk of Alcohol-Induced Pancreatitis With Cannabis Use.

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“Pancreatitis is an increasingly common clinical condition that causes significant morbidity and mortality. Cannabis use causes conflicting effects on pancreatitis development.

We conducted a larger and more detailed assessment of the impact of cannabis use on pancreatitis.

Concomitant cannabis and abusive alcohol use were associated with reduced incidence of acute and chronic pancreatitis (AP and CP).

Our findings suggest a reduced incidence of only alcohol-associated pancreatitis with cannabis use.”

https://www.ncbi.nlm.nih.gov/pubmed/30570765

https://onlinelibrary.wiley.com/doi/abs/10.1111/acer.13929

Heterogeneity of cannabinoid ligand-induced modulations in intracellular Ca2+ signals of mouse pancreatic acinar cells in vitro.

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“We recently reported that a CB2R agonist, GW405833 (GW), reduced both the ACh-induced Ca2+ oscillations and the L-arginine-induced Ca2+ signal enhancement in mouse pancreatic acinar cells, suggesting that GW-induced inhibition may prevent the pathogenesis of acute pancreatitis.

In this study, we aim to evaluate the effects of other cannabinoid ligands on Ca2+ signaling in acinar cells.

In conclusion, CB2R agonists play critical roles in modulating Ca2+ signals in mouse pancreatic acinar cells, while other cannabinoid ligands modulate Ca2+ oscillations in a heterogeneous manner through a CB receptor or non-CB-receptor mechanism.”

https://www.ncbi.nlm.nih.gov/pubmed/30202013

https://www.nature.com/articles/s41401-018-0074-y

The cannabinoid 1 receptor antagonist, AM251, prolongs the survival of rats with severe acute pancreatitis.

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“It has recently been recognized that anandamide (arachidonylethanolamide), which is an endogeneous-cannabinoid (endocannabinoid), mediates septic shock.

Cannabinoid means a mind-active material in cannabis (marijuana).

Anandamide is mainly produced by macrophages. Cannabinoid 1 (CB1) receptor, which is one of the cannabiniod receptors, is also known to mediate hypotensive shock.

The role of endocannabinoids in the progression of acute pancreatitis is unclear. The aims of this study are to clarify their relationship and to find a new therapeutic strategy by regulating the endocannabinoid signaling in acute pancreatitis.

This is the first report to show that endocannabinoids are involved in the deterioration of acute pancreatitis and that the down-regulation of endocannabinoid signaling may be a new therapeutic strategy for severe acute pancreatitis.”

https://www.ncbi.nlm.nih.gov/pubmed/16141678

Cannabinoid receptor-1 blockade attenuates acute pancreatitis in obesity by an adiponectin mediated mechanism.

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“Obesity is a risk factor for increased severity of acute pancreatitis.

Adipocytes produce adiponectin, an anti-inflammatory molecule that is paradoxically decreased in the setting of obesity. We have shown that adiponectin concentration inversely mirrors the severity of pancreatitis in obese mice.

Cannabinoid receptor CB-1 blockade increases circulating adiponectin concentration. We, therefore, hypothesize that blockade of CB-1 would increase adiponectin and attenuate pancreatitis severity.

Rimonabant treatment significantly increased circulating adiponectin concentration in obese mice.

In obese mice, cannabinoid receptor CB-1 blockade with rimonabant attenuates the severity of acute pancreatitis by an adiponectin-mediated mechanism.”

https://www.ncbi.nlm.nih.gov/pubmed/19225848

Cannabinoid agonist WIN55,212 in vitro inhibits interleukin-6 (IL-6) and monocyte chemo-attractant protein-1 (MCP-1) release by rat pancreatic acini and in vivo induces dual effects on the course of acute pancreatitis.

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“Cannabinoids (CBs) evoke their effects by activating the cannabinoid receptor subtypes CB1-r and CB2-r and exert anti-inflammatory effects altering chemokine and cytokine expression. Various cytokines and chemokines are produced and released by rodent pancreatic acini in acute pancreatitis.

Although CB1-r and CB2-r expressed in rat exocrine pancreatic acinar cells do not modulate digestive enzyme release, whether they modulate inflammatory mediators remains unclear. We investigated the CB-r system role on exocrine pancreas in unstimulated conditions and during acute pancreatitis.

These findings provide new evidence showing that the pancreatic CB1-r/CB2-r system modulates pro-inflammatory factor levels in rat exocrine pancreatic acinar cells. The dual, time-dependent WIN55,212-induced changes in the development and course of acute pancreatitis support the idea that the role of the endogenous CB receptor system differs according to the local inflammatory status.”

https://www.ncbi.nlm.nih.gov/pubmed/20659297

Cannabinoid HU210 Protects Isolated Rat Stomach against Impairment Caused by Serum of Rats with Experimental Acute Pancreatitis

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“Acute pancreatitis (AP), especially severe AP, is a potentially lethal inflammatory disease of pancreas which often leads to extra-pancreatic complications, even multiple systemic organ dysfunctions. It has been reported that 52% of patients with acute pancreatitis develop acute gastrointestinal mucosal lesion (AGML) or stress ulcer.

For centuries, Cannabis plant and its extracts have been used to alleviate symptoms of gastrointestinal inflammatory diseases.

It has been established that D9-tetrahydrocannabinol, the major psychoactive component of Cannabis, exerts its primary cellular actions though two G protein-coupled receptors, cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptors.

Since then, these two receptors have been recognized as the major regulators of physiological and pathological processes. Cannabinoids can reduce gastrointestinal secretion, and the activation of CB1 receptor exhibits protective role against stress-induced AGML, but the mechanisms of their action remain elusive.

The results from this study prove that the inflammatory responses and the imbalance of the gastric secretion during the development of AP are responsible for the pathogenesis of AGML, and suggest the therapeutic potential of HU210 for AGML associated with acute pancreatitis.

Therefore, our experimental results suggest a novel mechanism in the onset of AGML and new therapeutic values of cannabinoids as supplement of anti-inflammatory therapy in acute pancreatitis.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3532296/

Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells

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“Acute pancreatitis is an inflammatory disease, which has several causes and symptoms and requires immediate medical attention.

The cannabinoid receptor type 2 (CB2R) is a G protein-coupled receptor that, in humans, is encoded by the CNR2 gene. CB2Rs are predominantly expressed in the periphery, especially in immune cells, suggesting that CB2R mediates the effects of cannabinoids mainly in the immune system.

Emerging evidence demonstrates that the blockade of intracellular Ca2+ signals may protect pancreatic acinar cells against Ca2+ overload, intracellular protease activation, and necrosis.

The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis.

Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca2+ oscillations and L-arginine-induced enhancement of Ca2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis.

These results suggest that a CB2R agonist may serve as a novel therapeutic strategy to prevent and/or treat acute pancreatitis. This conclusion is consistent with previous report that a CB2R agonist exhibits a protective effect on pathogenesis in an acute pancreatitis animal model. Our data showing a reduction of intracellular Ca2+ signaling by GW also provide a new target to interpret the role of CB2R agonists in treating acute pancreatitis in addition to CB2R-mediated anti-inflammation.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4949433/

Activation of cannabinoid receptor 2 reduces inflammation in acute experimental pancreatitis via intra-acinar activation of p38 and MK2-dependent mechanisms.

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“The endocannabinoid system has been shown to mediate beneficial effects on gastrointestinal inflammation via cannabinoid receptors 1 (CB(1)) and 2 (CB(2)).

These receptors have also been reported to activate the MAP kinases p38 and c-Jun NH(2)-terminal kinase (JNK), which are involved in early acinar events leading to acute pancreatitis and induction of proinflammatory cytokines.

Our aim was to examine the role of cannabinoid receptor activation in an experimental model of acute pancreatitis and the potential involvement of MAP kinases.

The unselective CB(1)/CB(2) agonist HU210 ameliorated pancreatitis in wild-type and CB(1)-/- mice, indicating that this effect is mediated by CB(2).

Furthermore, blockade of CB(2), not CB(1), with selective antagonists engraved pathology.

Stimulation with a selective CB(2) agonist attenuated acute pancreatitis and an increased activation of p38 was observed in the acini.

With use of MK2-/- mice, it could be demonstrated that this attenuation is dependent on MK2. Hence, using the MK2-/- mouse model we reveal a novel CB(2)-activated and MAP kinase-dependent pathway that modulates cytokine expression and reduces pancreatic injury and affiliated complications.”

https://www.ncbi.nlm.nih.gov/pubmed/23139224