Category Archives: Pancreatitis

Disrupted endocannabinoid signaling contributes to systemic inflammation in acute pancreatitis

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“Acute pancreatitis (AP) is an inflammatory disease that can lead to systemic complications in severe cases. The endocannabinoid system has emerged as a potential modulator of inflammation in AP.

We investigated the role of the endocannabinoid 2-arachidonoylglycerol (2-AG) and the cannabinoid receptors CB1 and CB2 during AP.

A severity-dependent decrease in circulating 2-AG was found both in patients and a murine AP model. Restoring 2-AG – by avoiding its degradation via monoacylglycerol lipase inhibitor or direct 2-AG administration – reduced local and systemic inflammation, modulated peritoneal macrophage polarization, and mitigated lung injury. Notably, endocannabinoid system effects were consistent across sexes.

Both cannabinoid receptors were involved in disease pathophysiology.

Genetic Cnr1 knockout and pharmacological CB2 blockade showed distinct and complementary roles of both receptors in regulating inflammation, immune infiltration, and pulmonary damage.

These findings highlight a protective role for 2-AG and highlight the endocannabinoid system – and cannabinoid receptors in particular – as a promising therapeutic target to modulate inflammation and reduce systemic complications in acute pancreatitis.”

https://pubmed.ncbi.nlm.nih.gov/42153289

“These findings raise the possibility that counteracting the inflammation-driven decline in endogenous 2-AG through pharmacological intervention may represent a promising therapeutic strategy for AP.”

“Our data clearly support a role for both CB1 and CB2 receptors in the pathophysiology of AP.”

“Overall, our study supports the ECS as promising therapeutic target to reduce inflammation and systemic complications in AP.”

https://pathsocjournals.onlinelibrary.wiley.com/doi/10.1002/path.70076

“The Diminished Availability of 2-AG in Aged Synaptic Terminals is Ameliorated by a Full-Spectrum Cannabis Extract with a High THC Content. This highlights the potential of high THC content extracts as therapeutic agents for restoring the decreased 2-AG levels observed in the aging brain.”

https://pubmed.ncbi.nlm.nih.gov/41880097

Dietary Cannabis Seed Supplementation Attenuates Inflammation and Pancreatic Injury in a Cerulein-Induced Acute Pancreatitis Mouse Model

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“Cannabis seed (CS), also known as hemp seed, is a nutrient-dense plant-derived food material rich in polyunsaturated fatty acids and bioactive components with reported anti-inflammatory properties. However, potential nutritional effects of CS on acute pancreatitis (AP), an inflammation-driven disease with limited dietary management strategies, have not yet been investigated.

In this study, we examined the effects of dietary CS extract in a cerulein-induced AP mouse model. CS extract (5, 10, or 50 mg/kg) or vehicle (dimethyl sulfoxide) was orally administered 1 h prior to cerulein injection, and mice were euthanized 6 h after the final challenge.

Oral supplementation with CS significantly attenuated AP severity, indicated by reducing pancreatic weight-to-body weight ratio, serum amylase and lipase activities, histopathological pancreatic injury, and pancreatic myeloperoxidase activity. CS administration alleviated AP-associated acute lung injury; markedly suppressing pancreatic mRNA expression of proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α. High-performance liquid chromatography analysis identified α-linolenic acid, an omega-3 polyunsaturated fatty acid, as a major nutritional component of CS extract.

Collectively, these findings suggest that CS supplementation may contribute to nutritional modulation of inflammatory responses and systemic organ injury in experimental AP, supporting its potential as a functional food ingredient in inflammation-associated pancreatic disorders.”

https://pubmed.ncbi.nlm.nih.gov/41751483

“In conclusion, the present study demonstrates that dietary supplementation with CS extract attenuates pancreatic inflammation, digestive enzyme leakage, and systemic organ injury in experimental AP. By modulating inflammatory responses and neutrophil-mediated tissue damage, CS shows potential as a functional food ingredient for nutritional management of inflammation-associated pancreatic injury.”

https://www.mdpi.com/1467-3045/48/2/221


Medical cannabis for the management of pain in chronic pancreatitis with recurrent exacerbations: a case report

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“Introduction: Control of pain in patients affected by chronic pancreatitis with recurrent exacerbations is a challenging condition, with conventional therapies often providing limited relief. This case report describes the use of medical cannabis as a novel approach in a patient with refractory chronic pancreatitis, contributing to the growing interest in alternative treatments for pain and inflammation in similar complex cases.

Case presentation: A 54-year-old woman with a 24-year history of chronic pancreatitis caused by recurrent acute pancreatitis presented with persistent, severe abdominal pain and recurrent exacerbations despite undergoing numerous conventional interventions, including cholecystectomy, enzyme supplementation, repeated endoscopic retrograde cholangiopancreatographies (ERCPs), and stent placements. Imaging and laboratory findings confirmed chronic pancreatitis, with evidence of Oddi sphincter stenosis and microlithiasis. The patient was initially managed with standard pain relief therapy, digestive enzymes, and endoscopic interventions, all of which failed to provide lasting relief. In February 2024, she began treatment with a medical cannabis formulation rich in Cannabidiol, under the supervision of her healthcare provider. This intervention led to substantial pain reduction, cessation of acute episodes, improved appetite, and enhanced quality of life.

Conclusion: This case illustrates that medical cannabis may offer a promising alternative for managing chronic pancreatitis, especially when conventional treatments prove ineffective. This outcome underscores the need for further research on cannabinoids as a therapeutic option in chronic pain and inflammation management for pancreatitis and other challenging conditions.”

https://pubmed.ncbi.nlm.nih.gov/40781340/

“This case illustrates the potential of medical cannabis as an effective treatment option for chronic, treatment-resistant pancreatitis, a condition notoriously difficult to manage with conventional therapies. The patient’s experience demonstrates how cannabinoids can provide substantial pain relief, reduce inflammation, and improve quality of life, even when standard interventions fail to yield lasting benefits. Her case underscores the importance of exploring alternative therapies for complex, chronic conditions like pancreatitis, suggesting that medical cannabis may offer a transformative option for patients with few viable treatment paths.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-025-00303-w

Cannabis Use and Outcomes in Patients with Chronic Pancreatitis: A National Inpatient Sample Analysis

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“Background and aims: Cannabis is a commonly used recreational and medicinal substance and has been shown to have anti-inflammatory and analgesic effects. Previous studies have shown that cannabis may reduce disease severity of pancreatitis. We aim to use nationally available data to further investigate the impact of cannabis on outcomes among patients with chronic pancreatitis (CP).

Methods: Nationwide Inpatient Sample (NIS) 2016-2020 was used to identify patients with CP. Patients were stratified based on the presence of cannabis use. Data was collected regarding patient demographics, comorbidities, and Charlson Comorbidity Index (CCI). The outcomes assessed were sepsis, acute kidney injury (AKI), deep vein thrombosis (DVT), pulmonary embolism (PE), intensive care unit (ICU) admission, acute pancreatitis (AP), pancreatic cancer, total charges, and length of stay. The relationships were analyzed using multivariate logistic regression.

Results: Out of 907,790 hospitalized patients in this study; 52,360 (5.8%) were cannabis users. After adjusting for confounding factors, cannabis use was associated with decreased odds of mortality (aOR=0.47, p<0.001), DVT (aOR=0.71, p<0.001), PE (aOR=0.622, p=0.002), ICU admission (aOR=0.705, p<0.001), pancreatic cancer (aOR=0.730, p=0.021). There was no difference in odds of AKI, sepsis or AP between the two groups.

Conclusions: Our study found that cannabis use is associated with reduced disease severity and better outcomes among patients hospitalized with CP. Further studies are needed to confirm our findings and explore the role of cannabinoids in pancreatitis.”

https://pubmed.ncbi.nlm.nih.gov/40580529/

https://jgld.ro/jgld/index.php/jgld/article/view/6066

Impact of cannabis consumption on perioperative outcomes in patients undergoing hepatobiliary and pancreatic surgery: a nationwide analysis

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“Background: There is paucity of high-quality data on the effect of cannabis consumption on perioperative outcomes after hepatobiliary and pancreatic (HPB) surgery.

Methods: Data from the Nationwide Inpatient Sample (2016-2020) were used. In-hospital complications, length-of-stay and hospitalisation charges were compared among patients undergoing HPB surgery.

Results: We identified 191,315 patients, of which 1705 (0.89 %) were cannabis consumers. Cannabis consumers were more likely to be male (67.5 % vs 50.2 %), younger, and Black (22.6 % vs 11.0); p < 0.001 for all. Multivariate analysis demonstrated a significantly lower risk of pneumonia (OR 0.54, 95 % CI 0.29-0.99) among cannabis consumers. There was no significant difference in risk of in-hospital mortality (OR 0.64, 95 % CI 0.31-1.30), acute kidney injury, hemodialysis, blood transfusion, vasopressor use, invasive and non-invasive mechanical ventilation, venous thromboembolism, portal vein thrombosis, intraabdominal abscess, peritonitis, surgical site infection, post-procedure haemorrhage/hematoma, wound dehiscence, liver failure, or sudden cardiac arrest. There was no significant difference in length-of-stay (mean 10.99 vs 9.69 days; p = 0.348) or hospitalisation costs ($49,444 vs $43,661; p = 0.109).

Conclusion: There is no significant difference in major perioperative complications after HPB surgery among patients with cannabis use disorder. Further, there is no significant difference in health services utilisation among consumers versus non-consumers.”

https://pubmed.ncbi.nlm.nih.gov/40324909/

https://www.hpbonline.org/article/S1365-182X(25)00550-7/abstract

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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Image result for Pancreas journal

“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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Image result for aps acta pharmacologica “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
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