Marijuana and sperm have a complicated and confusing relationship. Some studies have found that men who smoke marijuana have a higher sperm count. Other research has found they have a lower sperm count. Regardless, what’s decided is that the hundreds of chemicals in marijuana tinker with sperm on a deep level — and new research demonstrates why.

In a study released Thursday in Scientific Reports, a team from Denmark reveal that, for better or worse, the body’s sperm-making machinery knows how to recognize cannabinoids, the active chemicals in marijuana.

It turns out that there are far more signs of the endocannabinoid system in testicles and sperm cells than previously thought. Endocannabinoids are a network of neurotransmitters that are naturally manufactured by the body, but they bear a similarity to cannabinoids, the chemicals that occur naturally in cannabis, which are sometimes called exogenous cannabinoids by scientists. Both the endocannabinoids we make ourselves (called endogenous cannabinoids) and exogenous cannabinoids bind to cannabinoid receptors throughout the body.

In this study, after analyzing testicular tissue samples of the 15 men, the researchers found there are plenty of endocannabinoid receptors and endocannabinoids in the testicles and sperm cells, too.

That’s important because it tells us that humans’ sperm-production hardware is attuned to interacting with cannabinoid chemicals. So when we add exogenous cannabinoids into the mix after say a person smokes a bowl, it could have effects on how that sperm production machinery operates.

Those effects may have been overlooked before, says lead study author Niels Skakkebæk, Ph.D., an affiliate professor at the University of Copenhagen.

“Andrologists like me have for generations been focusing on other hormone aspects, but overlooked the possibility that endocannabinoids may participate in the normal sperm and hormone production,” he explained in a press release sent to Inverse. “I was surprised to find that endocannabinoids were so widely expressed in all cell types in the testis, both in the germ cells and the hormone-producing cells.”

This study found that there are signs of the endocannabinoid system in both testicular tissue and germ cells, showing that the machinery that the body uses during sperm production may also be affected by cannabinoids from marijuana. Photo by Chase Fade on Unsplash

Skakkebæk’s study was conducted on a small sample of 15 men with testicular germ cell cancer who agreed to have tissue samples of their testis analyzed by scientists. When they analyzed those samples, they found that testicular tissue and germ cells, which eventually become sperm, had three key ingredients of the endocannabinoid system: the actual endocannabinoid chemicals themselves, the receptors that they bind to, and enzymes that break those chemicals down.

In the tissue samples, they detected an endocannabinoid called 2-arachidonoylglycerol (2-AG), which is one of the primary parts of the endocannabinoid system. They also found genetic transcripts that code for the endocannabinoid receptors in germ cells along with evidence that enzymes that break down endocannabinoids were “abundantly present” in germ cells.

That shows that the body’s sperm manufacturing plant has “machinery to synthesize and metabolize endocannabinoids.” That suggests that this machinery may also be attuned to the extra cannabinoids that fill our bodies after smoking weed — though it’s unclear exactly what happens when we overload that system.

"I was surprised to find that endocannabinoids were so widely expressed in all cell types in the testis.

Skakkebæk notes that his entire study was inspired by work showing that marijuana could have negative impacts on sperm development in men who smoked at least once per week. “We did see a hint a couple of years ago, when we found that young Danish men, who had used marijuana, had significantly poorer sperm counts than their peers,” he added.

But there are other studies that suggest the relationship between marijuana and sperm quality is more nuanced. A paper released February in Human Reproduction examined 662 men who reported their marijuana use. Within that sample, 365 men who had smoked weed before had significantly higher sperm counts than the 297 who hadn’t.

That alone differentiates it from the 2015 study on Danish men that Skakkebaek refers to, but there was another key difference. To be counted as a marijuana user in this study, the men only had to report smoking weed in at least more than two joints (or the equivalent) in their entire lives.

Scientists are still studying how smoking marijuana impacts sperm count, but they've recently shown that the endocannabinoid system might be tightly tied to sperm production. Photo by GRAS GRÜN on Unsplash

Compared to the men in the Danish study who smoked once per week, that’s far less cannabinoid exposure — which could partially explain these results.

The lead author of that study, Feiby Nassan, Ph.D. a research fellow at Harvard’s T.H. Chan School of Public Health, offered two explanations for these results. One was that we shouldn’t be too hasty to draw conclusions from them (there could have been other factors influencing sperm count beyond smoking weed), but the other was that the amount of marijuana smoked has a big influence on sperm itself.

“Low levels of marijuana use could benefit sperm production because of its effect on the endocannabinoid system, which is known to play a role in fertility, but those benefits are lost with higher levels of marijuana consumption,” she explained.

Combined with Skakkebæk’s study, these new results point to just how tightly the endocannabinoid system and sperm production are tied. They’re literally built into one another on a biological level. In the future, we may finally be able to nail down exactly how smoking impacts that special relationship.

Abstract:

Heavy use of cannabis (marijuana) has been associated with decreased semen quality, which may reflect disruption of the endocannabinoid system (ECS) in the male reproductive tract by exogenous cannabinoids. Components of ECS have been previously described in human spermatozoa and in the rodent testis but there is little information on the ECS expression within the human testis. In this study we characterized the main components of the ECS by immunohistochemistry (IHC) on archived testis tissue samples from 15 patients, and by in silico analysis of existing transcriptome datasets from testicular cell populations. The presence of 2-arachidonoylglycerol (2-AG) in the human testis was confirmed by matrix-assisted laser desorption ionization imaging analysis. Endocannabinoidsynthesising enzymes; diacylglycerol lipase (DAGL) and N-acyl-phosphatidylethanolamine-specifc phospholipase D (NAPE-PLD), were detected in germ cells and somatic cells, respectively. The cannabinoid receptors, CNR1 and CNR2 were detected at a low level in post-meiotic germ cells and Leydig- and peritubular cells. Different transcripts encoding distinct receptor isoforms (CB1, CB1A, CB1B and CB2A) were also differentially distributed, mainly in germ cells. The cannabinoid-metabolising enzymes were abundantly present; the α/β-hydrolase domain-containing protein 2 (ABHD2) in all germ cell types, except early spermatocytes, the monoacylglycerol lipase (MGLL) in Sertoli cells, and the fatty acid amide hydrolase (FAAH) in late spermatocytes and post-meiotic germ cells. Our findings are consistent with a direct involvement of the ECS in regulation of human testicular physiology, including spermatogenesis and Leydig cell function. The study provides new evidence supporting observations that recreational cannabis can have possible deleterious effects on human testicular function.