Cannabis-like molecules in the body control sperm motility

A naturally occurring compound in the body called 2-arachidonoyl glycerol (2-AG) — one of the body's own cannabis-like molecules (endocannabinoids) — plays a significant role in male fertility. This study investigated how 2-AG controls sperm movement and the acrosome reaction (the process sperm use to penetrate an egg) in mice. Researchers found that caput epididymal sperm contained higher levels of 2-AG than caudal sperm, suggesting the compound is actively regulated as sperm mature. The key mechanism involves 2-AG triggering calcium influx into sperm cells, which drives their movement and activation.

The study identified four enzymes responsible for breaking down 2-AG: MAGL (monoacylglycerol lipase), ABHD2, ABHD6, and ABHD12. Of these, MAGL showed the strongest hydrolytic activity, while ABHD2 was the weakest. Crucially, the enzymes are located in different parts of the sperm cell — MAGL sits in the midpiece (the engine of sperm motility), while ABHD2 and ABHD6 are found in the acrosomal region. This means ABHD2's role in mice appears to be linked to acrosome exocytosis (fertilization readiness), not sperm movement — a notable difference from its known role in human sperm.

These findings have real-world implications for cannabis users: since cannabis-derived cannabinoids like THC and CBD directly interact with the endocannabinoid system, regular use could potentially interfere with the 2-AG signaling pathways that govern sperm motility and fertility. Beyond cannabis science, the research opens doors to non-hormonal male contraceptives by targeting MAGL or ABHD12, and could improve assisted reproductive technologies (ART) or help diagnose male infertility by monitoring 2-AG and hydrolase activity levels.