Targeting the Endocannabinoidome: A Novel Approach to Managing Extraintestinal Complications in Inflammatory Bowel Disease DOI Creative Commons
Dinesh Thapa,

Anshu Ghimire,

Leon N. Warne

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(4), С. 478 - 478

Опубликована: Март 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

Язык: 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

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(2), С. 148 - 148

Опубликована: Янв. 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

Язык: Английский

Процитировано

2
Targeting the Endocannabinoidome: A Novel Approach to Managing Extraintestinal Complications in Inflammatory Bowel Disease DOI Creative Commons
Dinesh Thapa,

Anshu Ghimire,

Leon N. Warne

и другие.

Pharmaceuticals, Год журнала: 2025, Номер 18(4), С. 478 - 478

Опубликована: Март 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

Язык: Английский

Процитировано

0