Searching for novel ligands for the cannabinoid and related receptors. DOI Open Access
Pritesh Kumar

Published: Jan. 1, 2015

The first purpose of the present dissertation was to apply a high throughput assay systematically screen library food and drug administration (FDA)-approved drugs as potential ligands for cannabinoid receptor 2 (CB2). A cell-based, homogenous time resolved fluorescence (HTRF) method measuring changes in intracellular cAMP levels validated found be suitable testing that may act on CB2. Among 640 FDA-approved screened, raloxifene, used treat/prevent post-menopausal osteoporosis, identified novel CB2 inverse agonist. reporting these results demonstrated by acting CB2, raloxifene enhances forskolin-stimulated accumulation concentration-dependent manner. Furthermore, data showed competes concentration-dependently specific [3H]CP-55,940 binding In addition, pretreatment caused rightward shift concentration-response curves agonists CP-55,940, HU-210, WIN55,212-2. Raloxifene antagonism is vi most likely competitive nature, shifts were parallel not associated with any efficacy discovery an agonist suggests it might possible repurpose this therapeutic indications which target. identifying also provides important mechanisms actions explain known effects raloxifene. second current study investigate ability third-generation selective estrogen modulators (SERMs) bazedoxifene lasofoxifene bind receptor. We have identified, time, target lasofoxifene. Our able compete enhanced accumulation. parallel, WIN55,212-2 without altering indicates bazedoxifene- lasofoxifene-induced nature. SERMs can potentially repurposed SERMs. third structure-activity relationships fatty acid amides activating desensitizing G protein-coupled 119, promising both type diabetes obesity. Using detailed potency analyses, degree saturation acyl chain charged head groups profound compounds activate 119. pretreatments 119 desensitize degrees desensitization correlate well their fourth use fragment-based approach, categorical-SAR (cat-SAR), model GPR119. are GPR119 confirmed experimentally agonists, four distinct cat-SAR models developed. leave-one out validation routine, best had overall concordance 99 %, sensitivity specificity 100 %. from in-depth fragment analysis several consistent previously reported relationship (SAR) analyses. Overall, while development highly predictive rapidly prospective applicability domain must taken into consideration. Moreover, demonstrating report expert system ligands, many agents.

Language: Английский

Enhancing Tetrahydrocannabinol’s Therapeutic Efficacy in Inflammatory Bowel Disease: The Roles of Cannabidiol and the Cannabinoid 1 Receptor Allosteric Modulator ZCZ011 DOI Creative Commons
Dinesh Thapa,

Mohan Patil,

Leon N. Warne

et al.

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

Citations

2
AGA Clinical Practice Update on Diagnosis and Management of Cannabinoid Hyperemesis Syndrome: Commentary DOI Open Access
Alberto Rubio–Tapia, Richard W. McCallum, Michael Camilleri

et al.

Gastroenterology, Journal Year: 2024, Volume and Issue: 166(5), P. 930 - 934.e1

Published: March 5, 2024

Language: Английский

Citations

16
The SNMMI Procedure Standard/EANM Practice Guideline for Pediatric Gastric Emptying DOI
Hollie Lai, Reza Vali,

Frederick D. Grant

et al.

Journal of Nuclear Medicine Technology, Journal Year: 2025, Volume and Issue: unknown, P. jnmt.125.269832 - jnmt.125.269832

Published: April 1, 2025

Language: Английский

Citations

0
The Role of Endocannabinoids in Physiological Processes and Disease Pathology: A Comprehensive Review DOI Open Access

Paulina Simankowicz,

Joanna Stępniewska

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(8), P. 2851 - 2851

Published: April 21, 2025

The endocannabinoid system is a complex communication involved in maintaining homeostasis various physiological processes, including metabolism, immune response, pain modulation, and neuroprotection. Endocannabinoids, mainly anandamide 2-arachidonoylglycerol, are natural ligands of the cannabinoid receptors CB1 CB2, which widely distributed throughout central nervous peripheral tissues. Their biosynthesis, degradation, interaction with other signaling pathways play crucial roles both health disease. This article provides comprehensive overview pathological endocannabinoids, discusses their potential as therapeutic targets, highlights recent advances endocannabinoid-based treatments.

Language: Английский

Citations

0
Obesity-associated inflammation countered by a Mediterranean diet: the role of gut-derived metabolites DOI Creative Commons
Melanie R. Florkowski,

Esther Abiona,

Karen M. Frank

et al.

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: June 24, 2024

The prevalence of obesity has increased dramatically worldwide and become a critical public health priority. Obesity is associated with many co-morbid conditions, including hypertension, diabetes, cardiovascular disease. Although the physiology complex, healthy diet sufficient exercise are two elements known to be combating this condition. Years research on Mediterranean diet, which high in fresh fruits vegetables, nuts, fish, olive oil, have demonstrated reduction numerous non-communicable chronic diseases diet. There strong evidence support an anti-inflammatory effect inflammation key driver obesity. Changes alter gut microbiota intricately intertwined human physiology, as microbiota-derived metabolites play role biological pathways throughout body. This review will summarize recent published studies that examine potential metabolites, short-chain fatty acids, bile trimethylamine-N-oxide, lipopolysaccharide, modulating after consumption Mediterranean-like These modulate through NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, toll-like 4 signaling, macrophage driven effects adipocytes, among other mechanisms.

Language: Английский

Citations

3
Rastafarianism: When Religious Beliefs Conflict With Medical Necessity—A Case Report and Review of the Literature Around an Ethically Complicated Case DOI Creative Commons
Matthew Flick, Casey Martinez, David C. Fipps

et al.

Case Reports in Psychiatry, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Background: Rastafarianism maintains that cannabis is a sacred element of the religious practice, and followers religion traditionally engage cautiously with western medicine. This case involves Mr. I, 72-year-old Rastafari male acute myelogenous leukemia (AML) hepatic decompensation, who developed delirium psychotic features which were initially managed quetiapine. His family expressed concerns psychotropic medications requested using dronabinol, synthetic cannabinoid, to manage his symptoms considering spiritual significance cannabinoids in culture. The psychiatry team's dissenting recommendations regarding dronabinol was met resistance, voiced they felt their beliefs not being respected considered bringing own marijuana products. Following an ethics consultation, compromise reached trial low-dose dronabinol. However, I's worsened, prompting discontinuation management olanzapine. Discussion: exemplifies complexities clinical care when conflict medical necessity. We discuss limited indications for potential adverse effects on delirium's behavioral symptoms. Concerns about fungal sensitization from cannabinoid products context immunosuppressive chemotherapy dysfunction are also explored. Moreover, we emphasize importance cultural sensitivity individuals view as therapeutic. Balancing ethical, evidence-based medicine through thorough discussion risks benefits essential optimal decision-making such ethical dilemmas.

Language: Английский

Citations

0
Dopamine, activation of ingestion and evaluation of response efficacy: a focus on the within-session time-course of licking burst number DOI Creative Commons
Paolo S. D’Aquila

Psychopharmacology, Journal Year: 2024, Volume and Issue: 241(6), P. 1111 - 1124

Published: May 4, 2024

Abstract Rationale Evidence on the effect of dopamine D1-like and D2-like receptor antagonists licking microstructure forced swimming response led us to suggest that (i) receptors plays a role in activating reward-directed responses (ii) level activation is reboosted based process evaluation efficacy requiring receptors. A main piece evidence support this hypothesis observation antagonist raclopride induces within-session decrement burst number occurring after contact with reward. The few published studies detailed analysis time-course measure were conducted our laboratory. Objectives aim review recapitulate discuss as behavioural substrate for study mechanisms governing ingestion, related processes, its relevance drug effects ingestion. Conclusions gathered so far suggests provides an important might provide decisive drugs However, further from independent sources necessary validate use proposed interpretation measure.

Language: Английский

Citations

2
Electroacupuncture improves low-grade duodenal inflammation in FD rats by reshaping intestinal flora through the NF-κB p65/NLRP3 pyroptosis pathway DOI Creative Commons
Yongli Han,

Zhaoxia Kang,

Shuwen Jin

et al.

Heliyon, Journal Year: 2024, Volume and Issue: 10(10), P. e31197 - e31197

Published: May 1, 2024

Electroacupuncture (EA) is an effective alternative for the treatment of functional dyspepsia (FD). It reduces low-grade duodenal inflammation and improves symptoms FD by downregulating expression NF-κB p65 NLRP3, but its mechanism needs to be elucidated. To examine regulatory effect electroacupuncture on intestinal flora p65/NLRP3 pyroptosis pathway in rats. The rat model was established via multi-factor stress intervention two weeks. rats were randomly divided into NC group, NF-kB inhibitor group (NF-κB BAY 11–7082 administered), EA + group. After 14 days treatment, sacrificed, protein mRNA levels p65, IκB, NLRP3 duodenum evaluated Western blotting assays real-time fluorescent quantitative PCR. Illumina MiSeq sequencing platform used analyze V4 region 16S rRNA gene predict genes. concentration short-chain fatty acids (SCFAs) feces assessed metabolomics. can decrease promote gastrointestinal motility This mediated inhibition pathway, increase alpha beta diversity gut microbiota duodenum, abundance beneficial bacteria at phylum genus levels, content SCFAs. protective against might involve multiple hierarchy pathways. may remodel inhibiting thereby improving

Language: Английский

Citations

1
Impact of cannabis use on presentation and treatment response in eosinophilic esophagitis DOI

Stephanie A. Borinsky,

Alexandra A Weir,

Sean LaFata

et al.

Diseases of the Esophagus, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 3, 2024

Cannabis use is becoming increasingly common, both for recreational and medical purposes. However, there a paucity of data regarding cannabis in the context eosinophilic esophagitis (EoE). We aimed to determine impact on presentation treatment response EoE. To this end, we conducted retrospective cohort study at large academic center newly diagnosed EoE patients age ≥ 12 years. Self-reported status, baseline characteristics, topical corticosteroids dietary therapy were extracted. Bivariate multivariable analyses used compare users non-users time diagnosis assess response. Of 983 patients, 80 reported using cannabis, with majority reporting daily administration by inhalation. Baseline symptoms peak eosinophil count similar between non-users; less likely have endoscopic findings exudates, edema, stricture, lower total Endoscopic Reference Score. On analysis, younger age, male sex, non-White race, psychiatric independently associated history stricture was non-use. Post-treatment symptom histologic responses though higher odds post-treatment inflammatory features use. In conclusion, despite presenting milder initial findings, exhibited greater after treatment, highlighting potential negative influence management.

Language: Английский

Citations

1
Chronic Abdominal Pain in Patients with Inflammatory Bowel Disease in Remission: A Continuing Challenge for Clinicians DOI
Natasha Klemm, Sarvee Moosavi

Digestive Diseases and Sciences, Journal Year: 2024, Volume and Issue: 69(12), P. 4336 - 4346

Published: Nov. 13, 2024

Language: Английский

Citations

1