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Related Experiment Video

Updated: Sep 21, 2025

Urinary Bladder Distention Evoked Visceromotor Responses as a Model for Bladder Pain in Mice
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Peripheral Cannabinoid-1 Receptor Blockade Ameliorates Cystitis Severity.

Liad Hinden1, Rami Ludyansky2, Sary Leidershnaider3

  • 1Obesity and Metabolism Laboratory, Department of Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.

Cannabis and Cannabinoid Research
|June 1, 2022
PubMed
Summary

Peripheral blockade of the cannabinoid-1 receptor (CB1R) effectively treated cyclophosphamide-induced cystitis in mice. This approach reduced bladder dysfunction and inflammation, suggesting a new therapeutic strategy for lower urinary tract symptoms (LUTSs).

Keywords:
cannabinoid-1 receptorcyclophosphamidecystitisendocannabinoid systemlower urinary tract symptoms

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Area of Science:

  • Urology
  • Pharmacology
  • Immunology

Background:

  • The endocannabinoid system (ECS) influences bladder function, presenting a potential target for treating lower urinary tract symptoms (LUTSs).
  • Conflicting evidence exists regarding the effects of ECS activation on the bladder, necessitating further investigation into targeted interventions.

Purpose of the Study:

  • To evaluate the therapeutic potential of blocking the peripheral cannabinoid-1 receptor (CB1R) in a mouse model of LUTSs.
  • To investigate the efficacy of a peripherally restricted CB1R antagonist in ameliorating cyclophosphamide (CYP)-induced cystitis.

Main Methods:

  • A cyclophosphamide (CYP)-induced cystitis model was established in female C57BL/6 mice.
  • Mice received the peripherally restricted CB1R antagonist JD5037 or vehicle for three consecutive days.
  • Bladder dysfunction was assessed via voiding spot assay (VSA), bladder-to-body weight ratio, and analysis of gene/protein expression and ECS tone.

Main Results:

  • Peripheral CB1R blockade with JD5037 significantly reduced urination events and normalized the bladder-to-body weight ratio in CYP-treated mice.
  • JD5037 treatment restored bladder ECS tone by modulating CB1R expression and endocannabinoid levels.
  • The treatment effectively reduced CYP-induced inflammation, evidenced by decreased levels of tumor necrosis factor alpha (TNFα).

Conclusions:

  • Peripheral CB1R blockade demonstrates significant therapeutic relevance in ameliorating CYP-induced cystitis.
  • These findings support the preclinical development of peripherally restricted CB1R antagonists for the clinical treatment of LUTSs.