O-307 Cannabidiol as a potential novel treatment for endometriosis by its anti-inflammatory and anti-oxidative effects in an experimental rat model
Authors: Okten S.B , Cetin C , Tok O.E , Guler E.M , Islek S , Ozcan P , Ficicioglu C 
Published: June 2022

Abstract

Study question
Can cannabidiol (CBD) - a nonpsychoactive constituent of the cannabis plant – be used in the treatment of endometriosis by its anti-inflammatory and anti-oxidative effects?

Summary answer
CBD appears to be a potential novel therapeutic agent in the treatment of endometriosis through inhibiting inflammation and decreasing oxidative stress in a dose-dependent manner.

What is known already
The endocannabinoid system (ECS) consists of various bioactive lipids that are produced endogenously which activate cannabinoid 1-2 receptors (CB1-2). Alterations in ECS are associated with many physiological and pathological conditions throughout the body including endometriosis. The events that play role in the development and growth of ectopic endometriotic implants are proliferation, angiogenesis, and inflammation. By their anti-inflammatory and anti-oxidative effects, phyto and synthetic cannabinoids had been investigated and started being used for diseases with similar mechanisms. CBD is a nonpsychoactive constituent of the cannabis plant which acts indirectly upon the CB-1 receptor and as an inverse agonist of CB-2 receptor.

Study design, size, duration
Endometrial implants were surgically induced in 36 female Wistar-Albino rats in the first surgery. After confirmation of endometriotic foci in the second surgery, the rats were randomized into four groups. Group 1 (leuprolide acetate group) was given a single 1 mg/kg subcutaneous injection of leuprolide acetate. Groups 2,3 and 4 were 5 mg/kg CBD, saline solution (control group), and 20 mg/kg CBD injected groups, respectively, and daily intra-peritoneal (i.p.) injections were applied for seven days.

Participants/materials, setting, methods
After 21 days from the second surgery, the rats were sacrificed and histopathological analysis of endometriotic lesions, total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), interleukin 1 (IL-1), interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-a) measurements in blood and peritoneal fluid samples, and immunohistochemical staining for TNF-a expression in endometriotic tissue were evaluated.

Main results and the role of chance
After treatment, significant reductions in TOS, OSI, IL-1, IL-6 and TNF-α levels in the blood and peritoneal fluid samples and TNF-α expression of endometriotic implants (p &lt; 0.01) and increased TAS (p &lt; 0.01) were found in the CBD 5mg/kg and leuprolide acetate groups.

Limitations, reasons for caution
The limitation is that this is an experimental rat model study.

Wider implications of the findings
This is the first study in the literature that evaluates the effects of a phytocannabinoid -CBD- on endometriosis in a rat model. With its anti-inflammatory and anti-oxidative effects and favorable safety and tolerability profile, it might be a candidate for a novel treatment in endometriosis.

Trial registration number
not applicable