Enhancing Tetrahydrocannabinol’s Therapeutic Efficacy in Inflammatory Bowel Disease: The Roles of Cannabidiol and the Cannabinoid 1 Receptor Allosteric Modulator ZCZ011

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(2), P. 148 - 148

Published: Jan. 23, 2025

Background/Objectives: Current inflammatory bowel disease (IBD) treatments focus on symptomatic relief, highlighting the need for innovative approaches. Dysregulation of cannabinoid 1 (CB1) receptor, part endocannabinoid system, is linked to colitis. While tetrahydrocannabinol (THC) alleviates colitis via CB1 activation, its psychotropic effects limit clinical use. ZCZ011, a CB1R allosteric modulator, and cannabidiol (CBD), non-psychoactive cannabinoid, offer alternatives. This study investigated combining sub-therapeutic THC doses with ZCZ011 or CBD in murine model dextran sodium sulphate (DSS)-induced Methods: Acute was induced 4% DSS 7 days, followed by 3 days water. Chronic modelled over 24 alternating concentrations. The combination 2.5 mg/kg 20 10 evaluated. Key markers were assessed determine efficacy safety, including activity index (DAI), inflammation, cytokine levels, GLP-1, organ health. Results: DSS-induced resulted increased DAI scores, cytokines, inflammation dysregulation GLP-1 ammonia. at significantly improved but ineffective 5 mg/kg. alone showed transient effects. However, either alleviated markers, restored colon integrity reestablished homeostasis. also maintained favourable haematological biochemical profiles, notable reduction colitis-induced elevated ammonia levels. Conclusions: demonstrates synergistic potential low-dose combined as novel, effective safer therapeutic strategy ulcerative

Language: Английский

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Perineural Invasion in Pancreatic Ductal Adenocarcinoma: From Molecules towards Drugs of Clinical Relevance

Cancers, Journal Year: 2022, Volume and Issue: 14(23), P. 5793 - 5793

Published: Nov. 24, 2022

Pancreatic ductal adenocarcinoma is one of the most threatening solid malignancies. Molecular and cellular mediators that activate paracrine signalling also regulate dynamic interaction between pancreatic cancer cells nerves. This reciprocal interface leads to perineural invasion (PNI), defined as ability invade nerves, similar vascular lymphatic metastatic cascade. Targeting PNI in might help ameliorate prognosis pain relief. In this review, modern knowledge has been analysed critically presented. We focused on molecular pathways promoting progression, with particular emphasis neuropathic generation, we reviewed current pharmacological inhibitors axis. represents a common hallmark PDAC correlates recurrence, poor patients. The among cells, immune nerves biologically relevant each stage disease stimulates great interest, but real impact administration novel agents clinical practice limited. It still early days for PNI-targeted treatments, further advanced studies are needed understand whether they could be effective tools setting.

Language: Английский

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Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

Biomedicines, Journal Year: 2022, Volume and Issue: 10(3), P. 631 - 631

Published: March 9, 2022

Antibiotic resistance has become an increasing challenge in the treatment of various infectious diseases, especially those associated with biofilm formation on biotic and abiotic materials. There is urgent need for new protocols that can also target biofilm-embedded bacteria. Many secondary metabolites plants possess anti-bacterial activities, phytocannabinoids Cannabis sativa L. varieties have reached a renaissance attracted much attention their anti-microbial anti-biofilm activities at concentrations below cytotoxic threshold normal mammalian cells. Accordingly, many synthetic cannabinoids been designed intention to increase specificity selectivity compounds. The structurally unrelated endocannabinoids found activities. Recent data suggest mutual communication between endocannabinoid system gut microbiota. present review focuses integrated some selected issues physiological pharmacological

Language: Английский

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Effects of microencapsulated blend of organic acids and botanicals on growth performance, intestinal barrier function, inflammatory cytokines, and endocannabinoid system gene expression in broiler chickens

Poultry Science, Journal Year: 2022, Volume and Issue: 102(3), P. 102460 - 102460

Published: Dec. 29, 2022

With restricted usage of growth-promoting antibiotics, identifying alternative feed additives that both improve intestinal barrier function and reduce inflammation is the center to chickens' health. This study examined effects a microencapsulated additive containing citric acid, sorbic acids, thymol, vanillin on status. A total 240 birds were assigned either commercial control diet or supplemented with 500 g/MT product. Birds raised by feeding 2-phase (starter, d 1 21; grower, 15 42). Growth performance was recorded weekly. At 21 42, gastrointestinal tract permeability evaluated FITC-dextran (FD4) oral gavage. Jejunum-specific functions Ussing chamber. Intestinal gene expression selected epithelial cell markers, tight junction (TJ) proteins, inflammatory cytokines, endocannabinoid system (ECS) markers determined RT-PCR. Statistical analysis performed using Student t test. Results showed significant improvement efficiency in blend organic acids botanicals. 21, jejunal FD4 lower group. Jejunal transepithelial resistance higher birds. TJs mRNA (CLDN1 ZO2) upregulated jejunum ileum birds, while CLDN2 downregulated cecum. Proliferating marker SOX9 expressed ceca. Goblet (MUC2) upregulated, Paneth (LYZ) ileum. Proinflammatory cytokine expressions IL1B, TNFA, IFNG jejunum, anti-inflammatory IL10 ileum, cecum, cecal tonsil. The ECS most regions. Together, these results demonstrated botanical supplementation reduced inflammation, improved function, thus chicken efficiency. activated may play role reducing tissue inflammation.

Language: Английский

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Unveiling the angiogenic effects of cannabinoids: Enhancers or inhibitors?

Biochemical Pharmacology, Journal Year: 2023, Volume and Issue: 215, P. 115686 - 115686

Published: July 16, 2023

Cannabinoids are compounds found in the cannabis sativa plant. Cannabinoids, such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have potential therapeutic benefits various medical conditions. Some can activate cannabinoid receptors type-1 -2 (CB1 CB2), that part of endocannabinoid system (ECS), alongside endocannabinoids their metabolic enzymes. The ECS regulates physiological cognitive processes is a target for wide range health conditions like chronic pain, anxiety, neurodegenerative diseases. Synthetic cannabinoids, associated with serious risks, including addiction, psychosis, death. Nonetheless, some these molecules also being explored pharmacological applications. Angiogenesis process forming new blood vessels from existing ones, crucial growth, repair, tissue maintenance. Dysregulation this several diseases, cancer, diabetic retinopathy reproductive pathologies, preeclampsia. Recent data suggests cannabinoids may affect angiogenesis. Here, we reviewed impact on pro-angiogenic factors, extracellular matrix enzymes inhibitors, immune-inflammatory responses, angiogenic pathways functional assays, focusing main each class: THC CBD phytocannabinoids, anandamide (AEA) 2-arachidonoylglycerol (2-AG) WIN-55, JWH-133, XLR-11, LYR-7 LYR-8, synthetic cannabinoids. Despite conflicting reports about actions phytocannabinoids angiogenesis, ability to modulate undoubtedly confirmed. This open therapeutical route angiogenesis-related pathologies. In addition, present anti-angiogenic cell models, hinting drugs.

Language: Английский

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Targeting the Endocannabinoidome: A Novel Approach to Managing Extraintestinal Complications in Inflammatory Bowel Disease

Pharmaceuticals, Journal Year: 2025, Volume and Issue: 18(4), P. 478 - 478

Published: March 27, 2025

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder marked by persistent gastrointestinal inflammation and spectrum of systemic effects, including extraintestinal manifestations (EIMs) that impact the joints, skin, liver, eyes. Conventional therapies primarily target intestinal inflammation, yet they frequently fail to ameliorate these complications. Recent investigations have highlighted complex interplay among immune system, gut, nervous system in IBD pathogenesis, thereby underscoring need for innovative therapeutic approaches. Methods: We conducted comprehensive literature search using databases such as PubMed, Scopus, Web Science, Science Direct, Google Scholar. Keywords “cannabinoids”, “endocannabinoid system”, “endocannabinoidome”, “inflammatory disease”, “extraintestinal manifestations” were used identify peer-reviewed original research review articles explore role endocannabinoidome (eCBome) IBD. Results: Emerging evidence suggests eCBome—a network comprising lipid mediators, receptors (e.g., CB1, CB2, GPR55, GPR35, PPARα, TRPV1), metabolic enzymes—plays critical modulating responses, maintaining gut barrier integrity, regulating inflammation. Targeting eCBome not only improves but also appears mitigate metabolic, neurological, complications arthritis, liver dysfunction, dermatological disorders. Conclusions: Modulation represents promising strategy management addressing both local components. These findings advocate further mechanistic studies develop targeted interventions leverage novel avenue

Language: Английский

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Impact of Cannabis Use on Deep Inferior Epigastric Perforator Autologous Breast Reconstruction: analysis of 719 patients and 1148 flaps

Annals of Plastic Surgery, Journal Year: 2025, Volume and Issue: 94(4S), P. S188 - S193

Published: April 1, 2025

Introduction Given recent efforts to legalize and decriminalize recreational marijuana, its use has become increasingly common in the plastic surgery patient population. Although cannabis generally been considered lower risk than of other substances, studies have suggested it may be associated with an increased surgical complication rate. The aims our study were (1) characterize extent (2) determine clinical effects cohort patients undergoing autologous breast reconstruction using deep inferior epigastric perforator (DIEP) flaps. Methods A retrospective was conducted adult who underwent DIEP flaps between January 2015 December 2023 by 5 surgeons at institution. Patients divided into 2 groups users nonusers. Univariate multivariable analyses performed assess outcomes groups. Results total 87 (12.1%) 632 nonusers included. 5-fold increase proportion from found. Cannabis significantly younger (47.5 vs 51.7, P < 0.001) had a higher body mass index (30.5 28.9, = 0.012). Postoperatively, readmission rate (8.0% 3.2%, 0.035) longer time last abdominal drain removal (21 17 days, 0.001). After controlling for confounders, logistic regression revealed as significant factor postoperative general hematoma (OR: 3.078, confidence interval [95% CI]: 1.265–7.491, 0.013), 3.098, 95% CI: 1.197–8.020, 0.020), 2.865, 1.098–7.475, 0.031). Conclusion To knowledge, this is largest examining receiving reconstruction. Our findings suggest that require greater care attention.

Language: Английский

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The Effect of Orally Administered Δ9-Tetrahydrocannabinol (THC) and Cannabidiol (CBD) on Obesity Parameters in Mice

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(18), P. 13797 - 13797

Published: Sept. 7, 2023

Prolonged cannabis users show a lower prevalence of obesity and associated comorbidities. In rodent models, Δ9-tetrahydrocannabinol (THC) cannabidiol (CBD) from the plant Cannabis sativa L. have shown anti-obesity properties, suggesting link between endocannabinoid system (ECS) obesity. However, oral administration route has rarely been studied in this context. The aim study was to investigate effect prolonged pure THC CBD on obesity-related parameters peripheral endocannabinoids. C57BL/6 male mice were fed with either high-fat or standard diet then received treatment ramping doses, namely 10 mg/kg for 5 weeks followed by 30 an additional weeks. Mice treated had attenuated weight gain improved glucose tolerance, improvement steatosis markers decreased hypertrophic cells adipose epididymal tissue. tolerance increased lipid metabolism liver tissues, but contrast THC, no markers. exclusively level 2-arachidonoylglycerol liver. These data suggest that consumption not CBD, ameliorates diet-induced metabolic parameters, possibly through mechanism tissue adaptation.

Language: Английский

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Targeting the Endocannabinoidome in Pancreatic Cancer

Biomolecules, Journal Year: 2022, Volume and Issue: 12(2), P. 320 - 320

Published: Feb. 17, 2022

Pancreatic Ductal adenocarcinoma (PDAC), the most common malignancy of pancreas, is an aggressive and lethal form cancer with a very high mortality rate. High heterogeneity, asymptomatic initial stages lack specific diagnostic markers result in end-stage diagnosis when tumour has locally advanced or metastasised. PDAC resistant to available chemotherapy radiation therapy treatments, making surgery potent curative treatment. The desmoplastic microenvironment contributes determining pathophysiology, immune response therapeutic efficacy. existing approaches such as FDA-approved chemotherapeutics, gemcitabine, abraxane folfirinox, prolong survival marginally are accompanied by adverse effects. Several studies suggest role cannabinoids anti-cancer agents. Cannabinoid receptors known be expressed pancreatic cells, higher expression reported patients. Therefore, pharmacological targeting endocannabinoid system might offer benefits cancer. In addition, emerging data that combination can increase transgenic murine models. This review provides overview regulation expanded system, endocannabinoidome, will explore potential this for novel anticancer approaches.

Language: Английский

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Pharmacohistory of Cannabis Use—A New Possibility in Future Drug Development for Gastrointestinal Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(19), P. 14677 - 14677

Published: Sept. 28, 2023

Humans have employed cannabis for multiple uses including medicine, recreation, food, and fibre. The various components such as roots, flowers, seeds, leaves been utilized to alleviate pain, inflammation, anxiety, gastrointestinal disorders like nausea, vomiting, diarrhoea, inflammatory bowel diseases (IBDs). It has occupied a significant space in ethnomedicines across cultures religions. Despite multi-dimensional uses, the global prohibition of by USA through introduction Marijuana Tax Act 1937 led prejudice about perceived risks cannabis, overshadowing its medicinal potential. Nevertheless, discovery tetrahydrocannabinol (THC), primary psychoactive compound endocannabinoid system renewed scientific interest understanding role modulating different conditions, disorders. Preparations combining cannabidiol THC shown promise mitigating gut symptoms anti-inflammatory motility-enhancing effects. This review revisits ethnomedicinal use emphasizes need further research determine optimal dosages, formulations, safety profiles cannabis-based medicines. also underscores future potential cannabinoid-based therapies leveraging expanded system, an endocannabinoidome, modulation ailments.

Language: Английский

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