Endometriosis is a Disease of Chronic Inflammation That Cannabis May Treat Very Well
New research has begun on using cannabinoids to stop the progress of endometriosis and treat its symptoms of inflammation and pain.
A leading Israeli research group announced that it will investigate the therapeutic potential of cannabis in endometriosis treatment. Research is significantly lacking in this area.
Endometriosis is recognized as a condition in which endometrial cells proliferate and grow in an abnormal fashion, resulting in migration of the tissue outside the uterus. Over the last decade cannabinoids have been suggested to inhibit this abnormal growth, and to restore the balance between cellular growth and cell death, which are programmed activities of the cell under normal conditions.
Image credit: Slave SPB
Given that the current medical treatments are marginally successful in relieving only some of the symptoms associated in endometriosis (i.e. pain), there is an unmet need for novel, successful therapeutic strategies. The etiology of endometriosis includes inflammation, cell proliferation and cell survival.
The first question that always arises when considering any substance for treatment potential is whether the receptors for that substance exist in the target tissue. Fortunately, both CB1 and CB2 receptors (and the enzymes that participate in endocannabinoid turnover) are expressed by many cell types in the human endometrium.
Additionally, the uterus contains a high concentration of anandamide, which is an endocannabinoid. This tells researchers that cannabinoids from the cannabis plant will also engage with tissues in the uterus.
Equally important are the studies that have been published describing the role of cannabinoids as anti-inflammatory and anti-proliferative agents. Both of these properties will help treat the symptoms endometriosis.
These studies have also demonstrated that THC has a biphasic effect, a phenomenon that seems to be repeating. At low concentrations (nanomolar range) it has pro-proliferative effect, and at higher concentrations (micromolar range) it has inhibitory effect on cell-proliferation.
It is therefore in these higher concentrations that THC would potentially be beneficial in endometriosis, to inhibit abnormal endometrial cell proliferation. In fact, one study addressed the role of cannabinoids in the proliferation of endometrial cells and showed that treatment with CB1 and CB2 agonist compound both in vitro and in vivo in a mouse model had anti-proliferative effect.
Since endometriosis is a chronic inflammatory disease, it is tempting to speculate that the anti-inflammatory effects of cannabinoids would be highly successful as a therapeutic strategy. Women suffering from endometriosis have elevated levels of circulating cytokines and other inflammatory markers, which constitutes a risk for development of autoreactivity (i.e. autoimmune disease).
Immune cells express CB2 in abundance and much less CB1, and it seems that the activation of CB2 receptors is central to the immunosuppressive effects of cannabinoids . This would be beneficial in case of endometriosis because the inflammation is rampant and out of control, and the goal would be to reduce it.
Granted, under specific conditions cannabinoids can also kick start the immune response, but this seems to be mediated via CB1 receptor activation. Therefore, development of cannabis-based modulators that are CB2 specific might be the winning strategy to downregulate the inflammatory response in endometriosis.
Research into the potential therapeutic benefit of cannabis-based medicine in endometriosis is only beginning. Since cannabinoids can bind to different cannabinoid receptors, but also non-cannabinoids receptors, and have a dose-dependent effect, a road to discovery is likely still a long one. Nevertheless, investigators that completed studies over the past decade, looking into cannabinoid-based therapy in endometriosis, have paved the way for future research.