Study: the endocannabinoid system regulates sperm development

The consequences of cannabis use on the male reproductive system point more to a negative effect on male fertility. And while cannabis does not cause irreversible damage, the endocannabinoid system plays a role in sperm development.

A study A clinical study carried out on 1215 Danes aged 18 to 28 found 28% fewer spermatozoa in participants who used cannabis at least once a week, compared with those who did not. However, the mechanism behind this correlation has not been identified. There are also evidence in vitro studies which suggest that cannabis reduces sperm quality, although the biological reasons are not explained.

What's the link between the endocannabinoid system and the male reproductive system?

A study published in Nature magazine in September 2019 investigated the complex link between the endocannabinoid system (ECS) and the male reproductive system, in order to determine in fine the potential impact of cannabis use on a man's fertility.

Scientists have discovered that the endocannabinoid system and the male reproductive system are closely linked. The researchers used immunohistochemistry to selectively reveal different components of the endocannabinoid system in different cell types of the male reproductive system, at different stages of sperm formation. This revealed which components of the endocannabinoid system - receptors, enzymes and neurotransmitters - play a role in the processes of the male reproductive system.

Spermatozoa result from a process called spermatogenesis, during which germ cells called spermatogonia undergo mitosis and meiosis (cell division) to produce spermatozoa.

Different components of the endocannabinoid system are thus expressed at different stages of spermatogenesis. This differential expression suggests that the endocannabinoid system could be used to regulate sperm production. Interestingly, components of the endocannabinoid system were most strongly expressed in the later stages of spermatogenesis, when mature spermatozoa are formed.

«I was surprised to find that endocannabinoid [components] were so widely expressed in the different cell types of the testis, in both germ cells and hormone-producing cells. Andrologists like myself have been focusing on other hormonal aspects for generations, but have overlooked the possibility that endocannabinoids may be involved in normal sperm and hormone production,» said Niels Skakkebaek, lead author of the study.

What are the consequences for cannabis users?

The effects of cannabis on fertility are still poorly understood. The most important conclusion of the present study is that the endocannabinoid system and the male reproductive system are intimately linked. The endocannabinoid system appears to regulate sperm production and is particularly active in the later stages of spermatogenesis, during the formation of mature spermatozoa.

If the endocannabinoid system regulates sperm production, cannabis use could disrupt this process. Researchers believe that CB1 receptors may play an important role in facilitating the transition of immature sperm through meiosis. The THC present in cannabis activates CB1 receptors and may therefore disrupt sperm formation.

The researchers also discovered endocannabinoid components of interest to CBD users, including anandamide and fatty acid amide hydrolase (FAAH), at different stages of sperm production. These were particularly expressed in the later stages of spermatogenesis. The use of CBD inhibits the degradation of FAAH, thereby increasing levels of this enzyme and, in turn, of FAAH.’anandamide. Since these compounds play an important role in sperm production, CBD use could also disrupt this process.

Future research may uncover a mechanism by which cannabis affects the sperm production process, the quality of a man's sperm and the male reproductive system in general. For now, the link between the endocannabinoid and the male reproductive system may be enough to convince some cannabis users to abstain when trying to conceive, especially when they encounter difficulties on one side or the other.