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The endocannabinoid system — a target for the treatment of LUTS?

Nature Reviews Urology volume 13, pages 463–470 (2016)Cite this article

Subjects

Key Points

  • Endogenously produced cannabinoids (termed 'endocannabinoids') can modify the micturition process in animal models

  • Activation of cannabinoid receptors by endocannabinoids reduces the firing of bladder sensory nerves and decreases micturition frequency in rodent models of inflammatory bladder hyperalgesia

  • Based on data from these models, the endocannabinoid system might influence sensory dysfunction during bladder pathologies

  • Local endocannabinoid and/or fatty-acid ethanolamide signals are recruited in models of bladder inflammation

  • Data obtained from rats with bladder overactivity or from patients with detrusor overactivity and/or bladder pain implicate neuronal cannabinoid receptor 1 plasticity in the pathophysiology of chronic bladder dysfunctions

  • Blockade of endocannabinoid degradation and fatty-acid ethanolamides by fatty-acid amide hydrolase inhibitors has been shown to ameliorate bladder disorders in various experimental models, but no information is currently available regarding humans

Abstract

Lower urinary tract symptoms (LUTS) are common in all age groups and both sexes, resulting in tremendous personal suffering and a substantial burden to society. Antimuscarinic drugs are the mainstay of symptom management in patients with LUTS, although their clinical utility is limited by the high prevalence of adverse effects, which often limit patients' long-term adherence to these agents. Data from controversial studies in the 1990s revealed the positive effects of marijuana-based compounds on LUTS, and sparked an interest in the possibility of treating bladder disorders with cannabis. Increased understanding of cannabinoid receptor pharmacology and the discovery of endogenous ligands of these receptors has prompted debate and further research into the clinical utility of exogenous cannabinoid receptor agonists relative to the unwanted psychotropic effects of these agents. Currently, the endocannabinoid system is considered as a potential drug target for pharmacological management of LUTS, with a more favourable adverse event profile than antimuscarinic agents.

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Figure 1: Functional organization of the endocannabinoid system during normal micturition.
Figure 2: Functional organization of the endocannabinoid system during bladder dysfunction.
Figure 3: Functional organization of CB1 expression in experimental models of bladder overactivity.

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Authors and Affiliations

  1. Division of Drug Research, Department of Medical and Health Sciences, Linköping University, Linköping, 581 83, Sweden

    Petter Hedlund

  2. Department of Urology, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, Munich, 81377, Germany

    Christian Gratzke

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  1. Petter Hedlund
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Both authors contributed equally to the researching data, writing, and editing and or reviewing of this manuscript prior to submission.

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Correspondence to Christian Gratzke.

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Hedlund, P., Gratzke, C. The endocannabinoid system — a target for the treatment of LUTS?. Nat Rev Urol 13, 463–470 (2016). https://doi.org/10.1038/nrurol.2016.110

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