The Interplay of the Endocannabinoid System and Sperm Production

Written by Riley Kirk

One of the concerns with Cannabis use is the decreased quality of semen in men and an increased risk of testicular germ cell cancer.[1] Researchers at the University of Denmark are conducting studies to clear up some of the questions about how Cannabis interferes with male fertility.  Using Cannabis products produces pharmacological effects in our bodies by acting on the endocannabinoid system (ECS). Therefore, to gain more information on the interaction between both plant-derived cannabinoids and the endocannabinoids produced in our bodies, the researchers studied the expression of endocannabinoid system (ECS) components within the tissues and cells of the human testes. This included the cannabinoid receptors 1 and 2 (CB1 and CB2), the enzymes that produce the endocannabinoids, and the enzymes that break down endocannabinoids. [2] The goal of this study was to investigate at which stages of sperm production the ECS components begin to be expressed and determine if other reproductive cells contain components of the ECS.

The researchers were able to use specific antibody staining techniques to map where the different components of the ECS were in tissues from human testes. This allowed a visual representation of receptors and enzymes present in developing sperm cells. By investigating both germ cells at various stages of spermatogenesis and somatic cells, we know that there is a stage-specific expression of the ECS components as the sperm matures; the most robust expression of the ECS components was detected in post-meiotic spermatids. [1]

Previous reports had highlighted the presence of CB1 receptors in human spermatogonia, but this was the first study to emphasize the presence of both CB1 and CB2 receptor expression. Multiple detection methods confirmed this. There remain questions about which isoforms of the cannabinoid receptors are present due to specific methodology limitations. Both enzymes responsible for producing the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were detected in tissue of the testes, but only the 2-AG molecule was seen in the samples and at very low concentrations. 2-AG needs to be removed from a specific channel to facilitate sperm fertilization. The enzymes that remove 2-AG were also detected in spermatogonia but not in early-stage spermatocytes, indicating the involvement of the ECS in reproductive cells before meiosis. [3]

Notably, the expression of the synthesizing and degrading enzymes of the ECS were not constantly expressed in the reproductive cells. Instead, the expression patterns were different depending on the growth stage of the sperm. This suggests that endocannabinoids are likely involved in the regulation of spermatogenesis, and therefore disruption of normal ECS functions could result in impaired sperm production.




[1] Nielsen JE, et al. Characterization and localization of the endocannabinoid system components in the adult human testis. Sci Rep. 2019; 9 (12866): 10.1038/s41598-019-49177-y. Times cited = 17. Journal impact factor = 3.998.

[2] Lu H, et al. An introduction to the endogenous cannabinoid system. Biol Psychiatry. 2016; 79 (7): 10.1016/j.biopsych.2015.07.028. Times cited = 509. Journal impact factor = 12.095.

[3] Miller MR, et al. Unconventional endocannabinoid signaling-governs sperm activation via the sex hormone progesterone. Science. 2017; 352 (6285): 10.1126/science.aad6887. Times cited = 140. Journal impact factor = 41.845.

About the author

Riley Kirk