1. Medicine
  2. Neuroscience
Download icon

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
Short Report
  • Cited 4
  • Views 3,595
  • Annotations
Cite this article as: eLife 2020;9:e50356 doi: 10.7554/eLife.50356

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.

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.

Metrics

  • 3,595
    Page views
  • 356
    Downloads
  • 4
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Computational and Systems Biology
    2. Medicine
    Amit Frishberg et al.
    Research Article Updated

    Human diseases arise in a complex ecosystem composed of disease mechanisms and the whole-body state. However, the precise nature of the whole-body state and its relations with disease remain obscure. Here we map similarities among clinical parameters in normal physiological settings, including a large collection of metabolic, hemodynamic, and immune parameters, and then use the mapping to dissect phenotypic states. We find that the whole-body state is faithfully represented by a quantitative two-dimensional model. One component of the whole-body state represents ‘metabolic syndrome’ (MetS) – a conventional way to determine the cardiometabolic state. The second component is decoupled from the classical MetS, suggesting a novel ‘non-classical MetS’ that is characterized by dozens of parameters, including dysregulated lipoprotein parameters (e.g. low free cholesterol in small high-density lipoproteins) and attenuated cytokine responses of immune cells to ex vivo stimulations. Both components are associated with disease, but differ in their particular associations, thus opening new avenues for improved personalized diagnosis and treatment. These results provide a practical paradigm to describe whole-body states and to dissect complex disease within the ecosystem of the human body.

    1. Medicine
    2. Neuroscience
    Ekemini AU Riley, Randy Schekman
    Feature Article

    The Aligning Science Across Parkinson’s (ASAP) initiative was set up to improve understanding of the biology underlying the onset and progression of Parkinson’s disease. With an emphasis on open science and collaboration, we have assembled a research network led by nearly 100 investigators to explore the pathology of Parkinson’s disease, and this network will soon expand to include researchers working on relevant (dys)-functional neural circuits. We have also contributed to large-scale genetics and patient cohort initiatives related to the disease. We hope that these actions, and others planned for the future, will deepen our knowledge of the molecular mechanisms underlying the origin and evolution of Parkinson’s disease and, ultimately, contribute to the development of novel therapies.