Disease-modifying effects of natural Δ9-tetrahydrocannabinol in endometriosis-associated pain
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
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.
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
-
- 5,880
- views
-
- 575
- downloads
-
- 31
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.