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

Escudero-Lara et al. ·eLife Impact 1.6

Clear benefit GRADE Very low 39 citations

SamplePräklinisch

Durationunclear

ControlUntreated control group

EndpointMechanical hypersensitivity

Blindingn.a.

DesignPräklinisch (Mausmodell)

Cannabinoidthc

Key finding

THC alleviated mechanical hypersensitivity, pain and memory deficits and inhibited the development of endometrial cysts in the mouse model.

Summary

Mouse model of surgically induced endometriosis; daily THC (2 mg/kg) alleviates mechanical hypersensitivity and pain unpleasantness, restores cognitive function and inhibits the development of endometrial cysts. Preclinical translational data without clinical human studies.

PopulationFemale mice with surgically induced endometriosis (mouse model)

InterventionΔ9-Tetrahydrocannabinol (THC) 2 mg/kg daily, systemic

ControlUntreated control group (mouse model)

OutcomeTHC alleviated mechanical hypersensitivity and pain unpleasantness, inhibited the development of endometrial cysts, modified uterine innervation and restored cognitive function; no effect on the anxiogenic phenotype

Confidence in the evidence

Very low

The lowest GRADE level, the effect estimate remains uncertain.

Downgraded for

Indirectness

Quality profile

Sample size —

Blinding —

Effect size Clear benefit

Citations / year ★★★★★

Authors

Escudero-Lara A, Argerich J, Cabañero D, Maldonado R

DOI 10.7554/elife.50356↗

Design: Präklinisch (Mausmodell)

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 Delta9-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.

The impediment to action advances action. — Marcus Aurelius