The Female Endocannabinoid System: An Important Future Point Of Insight

Dr. Zac Pilossoph

As each day goes by, it seems like cannabis and the endocannabinoid system are found to have some relationship to yet another physiologic mechanism or process. However, surprisingly, as the research catches up to the subjective reports, the facts behind the claims are truly validated at a consistent rate. One relatively new but interesting topic within this conversation is the relationship between the endocannabinoid system and the female reproductive tract.

From the very beginnings, cannabis has played a role in the treatment or palliation of female reproductive system dysregulation. In fact, several texts, dating back to the 15th century BCE, document the beneficial use of cannabis via both local suppository and systemic applications. Some of the strongest pieces of2 evidence for this come from the 15th century, where hemp cloths were applied by mid-wives post-cesarian section for pain and inflammation relief, and in 18th century where there was the chronological documentation by Sir J Russell Reynolds of cannabis being used by Queen Victoria for the amelioration of menstrual cramps. Now of course, during these times, the exact reason for why cannabis worked for yet another body system was unclear. However, also like most medical cannabis users then and now, the underlying physiology was not questioned, but simply trusted.

Today, with the advancement of cannabis research, scientists have begun to dive deeper into this subjective phenomenon in order to correlate causation and build understanding. The first amazing finding in both animal and human studies, is that the reproductive system contains the second highest concentration of endocannabinoid receptors (CB1, CB2, along with other overlapping receptor types) second only to the central nervous system (brain and spinal cord). Via various cell staining techniques, endocannabinoid receptors have been proven to be found in every cell type and tissue within this body system, with different concentrations at each location at different points of maturation. The superficial uterine lining seems to be of the site with the highest concentration above all else. Discoveries have also elucidated the differential production and expressions of both endogenous endocannabinoids (AEA, 2-AG, among others) and their respective receptors based on stage of a woman’s fertility cycle. What this means is that endocannabinoids are playing an integral role in the development and regulation of fertile ovum production, ovulation, placentation, embryogenesis, etc. Furthermore, there is a proven relationship between the density of endocannabinoid receptors and estrogen production, with estrogen appearing to be a positive influencer on Endocannabinoid function and progesterone the opposite. Now, as they always say “further research is needed to confirm these claims” but for now, the subjective reports and objective findings are quite promising.

So, where does this lead us with respect to more advanced and applied treatment options for women? Well, by understanding and digesting what the research is suggesting, cannabis can yet again be considered and applied in the proper manner for certain conditions, no different than standard pharmacologic options, if done responsibly and with prospective documentation. One of the most promising applications is and will continue to be in response to dysmennorhea symptoms, or menstruation. According to reports, up to 80% of women suffer from noticeable dysmennorhea symptoms on a regular basis, with over 20% affected so severely that their quality of life for more than one day is considerably reduced. The numerous effects of dysmenorrhea varies between individuals, but can include a myriad of cramps, nausea, sensitivity to touch, migraine, and generalized anxiety/irritability secondary to pain and inflammation. Cannabis, through its anti-inflammatory and pain reduction mechanisms, is thought to be able to neutralize these symptoms via the physiologic mechanisms by which they are created. For example, prostaglandins are the primary molecule produced by the body to induce an inflammatory response, as well as promote the contractions in the uterus during menstruation. Cannabis has the ability to block the enzymes responsible for this process, thus leading to symptom relief, without causing various side-effects in other organs like many of the current pharmacologic options often do (i.e. NSAIDs).

Another proposed, but still early use of cannabis with relation to the female reproductive tract is for the treatment of cancer, specifically ovarian cancer. Based on the receptor location, as well as the generalized molecular signaling that occurs within the environment of malignant cancer cells, cannabis is set to play a potential role in the multimodal treatment options for various cancer types. In conjunction, given that the ovaries are known to be endocannabinoid system dense via receptors and endogenous endocannabinoids, the addition of systemic exogenous cannabis will be an interesting and prospectively useful option for halting tumor cell growth and even potentially causing cell death via specific cell receptor binding.

Now of course, along with this, there is undoubtedly an opposite argument for the application of cannabis in women with respect to reproductive system benefit. Of most important is the inter-relation between the endocannabinoid system and normal physiologic follicular-ovulation cycling. Specifically, it is proposed in several articles that exogenous cannabinoids may interfere with the delicate balance hormonal feedback between the brain and reproductive system, thus potentially reducing overall fertility with long-term use of cannabis. Again, further research is needed for this topic as for several others, but at present, this is definitely an appropriate area for debate with regards to the balance of benefit vs. harm in the medical and therapeutic use of cannabis.

Each day is most definitely a new and exciting day for the ever-evolving cannabis community. The research continues to grow in all sectors, the product development and selection continues to expand, and both the subjective and objective reports continue to build as time and efforts go on. The appropriate applications and uses for conditions associated with female reproductive system dysregulation will without a doubt be a part of this conversation, as seen here and by the dozens of articles out there as well. Only time will tell where we end up, but for now, let us keep promoting responsible education and research, so that thousands of women may eventually be able to have yet one more option in the medicine cabinet for trustworthy medical and therapeutic use.

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