Disease-modifying effects of natural Δ9-tetrahydrocannabinol in endometriosis-associated pain

  1. Alejandra Escudero-Lara
  2. Josep Argerich
  3. David Cabañero  Is a corresponding author
  4. Rafael Maldonado  Is a corresponding author
  1. Universitat Pompeu Fabra, Spain

Abstract

Endometriosis is a chronic painful disease highly prevalent in women that is defined by growth of endometrial tissue outside the uterine cavity and lacks adequate treatment. Medical use of cannabis derivatives is a current hot topic and it is unknown whether phytocannabinoids may modify endometriosis symptoms and development. Here we evaluate the effects of repeated exposure to Δ9-tetrahydrocannabinol (THC) in a mouse model of surgically-induced endometriosis. In this model, female mice develop mechanical hypersensitivity in the caudal abdomen, mild anxiety-like behavior and substantial memory deficits associated with the presence of extrauterine endometrial cysts. Interestingly, daily treatments with THC (2 mg/kg) alleviate mechanical hypersensitivity and pain unpleasantness, modify uterine innervation and restore cognitive function without altering the anxiogenic phenotype. Strikingly, THC also inhibits the development of endometrial cysts. These data highlight the interest of scheduled clinical trials designed to investigate possible benefits of THC for women with endometriosis.

Data availability

All data supporting the findings of this study are available within the manuscript and its source data files. Source data files have been provided for Figures 1, 2, 3 and 4 and their figure supplements.

Article and author information

Author details

  1. Alejandra Escudero-Lara

    Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  2. Josep Argerich

    Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  3. David Cabañero

    Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
    For correspondence
    david.cabanero@upf.edu
    Competing interests
    The authors declare that no competing interests exist.
  4. Rafael Maldonado

    Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain
    For correspondence
    rafael.maldonado@upf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4359-8773

Funding

Instituto de Salud Carlos III (RD16/0017/0020)

  • Rafael Maldonado

Ministerio de Ciencia, Innovacion y Universidades (SAF2017-84060-R-AEI/FEDER-UE)

  • Rafael Maldonado

Generalitat de Catalunya - Agencia de Gestio d'Ajuts Universitaris i de Recerca (2017-SGR-669)

  • Rafael Maldonado

Generalitat de Catalunya - Agencia de Gestio d'Ajuts Universitaris i de Recerca (ICREA Academia 2015)

  • Rafael Maldonado

Generalitat de Catalunya - Agencia de Gestio d'Ajuts Universitaris i de Recerca (2019FI_B2_00111)

  • Alejandra Escudero-Lara

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal procedures were conducted in accordance with standard ethical guidelines (European Communities Directive 2010/63/EU and NIH Guide for Care and Use of Laboratory Animals, 8th Edition) and approved by autonomic (Generalitat de Catalunya, Departament de Territori i Sostenibilitat) and local (Comitè Ètic d'Experimentació Animal, CEEA-PRBB) ethical committees.

Reviewing Editor

  1. Allan Basbaum, University of California, San Francisco, United States

Publication history

  1. Received: July 19, 2019
  2. Accepted: December 26, 2019
  3. Accepted Manuscript published: January 14, 2020 (version 1)
  4. Version of Record published: January 23, 2020 (version 2)

Copyright

© 2020, Escudero-Lara et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Alejandra Escudero-Lara
  2. Josep Argerich
  3. David Cabañero
  4. Rafael Maldonado
(2020)
Disease-modifying effects of natural Δ9-tetrahydrocannabinol in endometriosis-associated pain
eLife 9:e50356.
https://doi.org/10.7554/eLife.50356

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    Funding: financial support for this work from a Vanier Canada Graduate Scholarship from the Canadian Institutes of Health Research (GIG), an Ontario Graduate Scholarship (SS), a Restracomp Research Fellowship provided by the Hospital for Sick Children (SS), an Institutional Research Chair in Neuroinformatics (MD), as well as a Natural Sciences and Engineering Research Council CREATE grant (MD).