Key endocannabinoid enzymes in the human uterine lining change expression across the menstrual cycle, with peak levels of degrading enzymes during the implantation window, suggesting endocannabinoid tone drops when embryos need to implant.
Read this if you are trying to conceive and use cannabis, or are interested in the reproductive biology of endocannabinoids.
Endocannabinoid-degrading enzymes peak during the implantation window
What the researchers found
Researchers mapped endocannabinoid system components in the uterine lining of 49 regularly cycling women. They measured both synthetic enzymes (that produce endocannabinoids) and degrading enzymes (that break them down) across the menstrual cycle.
During the secretory phase (when implantation occurs), the synthetic enzyme NAPE-PLD increased in multiple cell types, while degrading enzymes FAAH and MAGL also increased in glandular tissue. The net effect of simultaneously increasing both production and degradation suggests a tightly controlled endocannabinoid environment during implantation.
COX-2, which oxidizes endocannabinoids, showed maximum expression during the proliferative phase and peaked in luminal cells during early secretory phase.
Why it matters
The endocannabinoid system appears to play a critical role in preparing the uterine lining for embryo implantation. Cannabis use during the implantation window could disrupt this precisely timed system, with implications for fertility.
The numbers in context
49 women; NAPE-PLD increased in luminal (p=0.001), stromal (p=0.007), glandular (p=0.04) cells during secretory phase; FAAH increased in glandular (p=0.009) and luminal (p=0.01) cells; COX-2 peaked in proliferative phase (p=0.002)
How the study worked
Observational study of endometrial biopsies from 49 regularly cycling women. Protein localization by immunohistochemistry and mRNA expression by real-time RT-PCR across menstrual cycle phases.
What this study cannot tell us
Measured enzyme expression rather than actual endocannabinoid levels. Did not study women using cannabis. Cross-sectional cycle phase comparisons rather than within-subject longitudinal tracking. The functional impact of these expression changes on implantation was not tested.
How to read the evidence
Well-designed molecular biology study of human tissue, but observational and did not directly test cannabis effects on implantation.
When this study was published
Published in 2015. Reproductive endocannabinoid research has continued to develop.
The bigger picture
If the uterine endocannabinoid system must be precisely calibrated for successful implantation, cannabis use could theoretically interfere with fertility by flooding the system with exogenous cannabinoids at the wrong time.
Questions still open
- Does cannabis use around the time of implantation reduce fertility? Could endocannabinoid system testing predict implantation receptivity for IVF? Would CBD affect these pathways differently than THC?
Common questions
Could cannabis affect fertility?
What is the implantation window?
Read the original research
Endocannabinoid regulation in human endometrium across the menstrual cycle.
Reproductive sciences (Thousand Oaks, Calif.), 22(1), 113-23
Citation
Scotchie, Jessica G; Savaris, Ricardo F; Martin, Caitlin E; Young, Steven L. (2015). Endocannabinoid regulation in human endometrium across the menstrual cycle.. Reproductive sciences (Thousand Oaks, Calif.), 22(1), 113-23. https://doi.org/10.1177/1933719114533730
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