What is the Endocannabinoid System?
The endocannaboid system - or ECS - is a complex physiological system in our body. In fact, it’s the master regulatory system of all the other physiological systems in the body. The ECS ensures that all systems are working together to maintain homeostasis, or balance.
The ECS is designed to direct traffic and ensure that the body and mind rebalance, regardless of external stressors.
How Does the ECS Affect the Menstrual Cycle?
The endocannabinoid system and the menstrual cycle are closely linked. The ECS is related to the reproductive systems of people who are born with a uterus. It influences monthly hormonal cycles, which in turn influence the function and tone of the ECS.
So, how do the menstrual cycle and the ECS speak to each other?
Phases of the Menstrual Cycle
Throughout the menstrual cycle, our bodies experience changes in the ovaries and endometrium (the inner lining of the uterus). Body temperature and hormones also shift. There are four phases of the menstrual cycle altogether.
The Follicular or Proliferative Phase
The follicular phase is the first half of the menstrual cycle, and includes menstruation.
During this phase, the follicle-stimulating hormone (FSH) stimulates the egg cell follicles to mature in the ovaries. These follicles produce a type of estrogen called estradiol.
As the primary follicle matures, estradiol levels peak at the end of the follicular phase.
During menstruation, the inner lining of the uterus (endometrium) is shed through the cervix and exits out of the vagina. This causes the endometrium to decrease in size.
Ovulation
Ovulation occurs in a 12-24 hour period in the middle of the menstrual cycle. During ovulation, the luteinizing hormone (LH) triggers the release of the egg cell from the mature follicle.
The Luteal or Secretory Phase
This is the second half of the menstrual cycle. The purpose of the luteal - or secretory - phase is to prepare the uterus to house a fertilized egg.
The egg cell travels from the ovaries down the fallopian tubes towards the uterus.
If it encounters a sperm cell in the fallopian tubes, conception can occur. If this happens, the fertilized egg will continue to travel down the fallopian tubes to the uterus. Once there, it implants in the endometrial wall.
During the luteal phase, the endometrial tissue in the uterus is regrowing in preparation for the fertilized egg to implant. Meanwhile, the empty follicle in the ovaries creates and secretes progesterone.
This supports the implantation of the fertilized egg and the early stages of pregnancy by ensuring that menstruation does not occur.
Menstruation
If the egg does not implant, progesterone production stops. This ends the luteal phase, and menstruation begins. Day one of menstruation is the end of the luteal phase.
The role of the Endocannabinoid System in the Reproductive Organs
Cannabinoid receptors and endocannabinoids are found in the ovaries, the fallopian tubes and the uterus.
Human egg cells have CB1 and CB2 receptors, which emerge while the egg cells develop in every cycle.
During the second half of the menstrual cycle, CB1 receptors increase in numbers and in activity. This is a process known as upregulation.
Hormonal Fluctuations in the ECS
The Follicular Phase
The activity of the endocannabinoid system fluctuates in response to monthly hormonal activity.
During the mid-follicular phase (the first half of the menstrual cycle, including menstruation) the CB1 receptors in the uterus decrease in activity and number. This is known as “downregulation”.
As the follicle is formed in the ovaries, the ECS activity in the ovaries increases. The mid-follicular to late luteal phase also brings an increase - or “upregulation” - in the number and activity of CB2 receptors in the ovaries.
Anandamide Levels and Fertility The endocannabinoid anandamide is present in both the ovaries and the fluids of the female reproductive tract.
Anandamide is involved in the creation and maturation of follicles and egg cells, as well as in the process of ovulation.
Right around ovulation (in the middle of a menstrual cycle), the enzyme that breaks down anandamide is at its lowest levels, and anandamide is at its highest levels.
During menstruation, the enzyme that breaks down anandamide is at its highest level, which causes anandamide levels to drop.
Key research has shown that anandamide inhibits aromatase activity. Aromatase is an enzyme responsible for the conversion of testosterone into estrogen.
This means that when anandamide levels are low, people who menstruate are less fertile.
Sensitivity Fluctuates Throughout the Menstrual Cycle
In human studies, people who are ovulating or in the second half of their menstrual cycles (when the CB1 receptors are more active) may be more sensitive to both the therapeutic and adverse effects of stimulators of these receptors, such as THC.
For instance, they might find that THC increases anxiety mid-cycle, or causes more drowsiness after consuming an edible. Therefore, during this time people may actually benefit from lower doses of THC and higher doses of CBD or CBG.
On the other hand, this could change during menstruation, when the CB receptors are downregulated.
People may find that slightly higher THC doses are more helpful, especially for managing menstrual pain and symptoms of PMS. CBD vaginal suppositories, like OVY, offer a particularly effective pain relief option by delivering CBD directly to cannabinoid receptors in the female reproductive system for targeted, localized drug delivery.
References
Brents L. K. (2016). Marijuana, the Endocannabinoid System and the Female Reproductive System. The Yale journal of biology and medicine, 89(2), 175–191.
Clark, C. S. (2021). Cannabis: A handbook for nurses. Wolters Kluwer.
Critchley, H. O. D., Williams, A. R. W., Armstrong, G. M., & Maybin, J. A. (2020, April 29). Physiology of the endometrium and regulation of menstruation. 100 (3). https://doi.org/10.1152/physrev.00031.2019
Lu, H. C., & Mackie, K. (2016). An Introduction to the Endogenous Cannabinoid System. Biological psychiatry, 79(7), 516–525. https://doi.org/10.1016/j.biopsych.2015.07.028
Scotchie, J. G., Savaris, R. F., Martin, C. E., & Young, S. L. (2015). Endocannabinoid regulation in human endometrium across the menstrual cycle. Reproductive sciences (Thousand Oaks, Calif.), 22(1), 113–123. https://doi.org/10.1177/1933719114533730