Human Brain Chemical Inhibits Sea-Urchin Spermin Same Way As Active Ingredient In Marijuana

BUFFALO, N.Y. -- University at Buffalo researchers have discovered that anandamide, a human brain chemical, produces the same negative effect on fertility in sea-urchin sperm as delta-9-tetrahydracannabinol (THC), the active ingredient in marijuana, by prohibiting the sperm from fertilizing the egg.

The finding could shed new light into the causes of infertility and other essential organic functions at the cellular level.

Herbert Schuel, Ph.D., professor of anatomy and cell biology at UB and head of the research team, said anandamide may act by binding to the sperms’ cannabinoid receptor. If so, the chemical, known to be the natural link, or ligand, for the cannabinoid receptor in the human brain, also could be the natural ligand for the cannabinoid receptor in sea-urchin sperm.

If anandamide is the body’s version of THC, further research may show that it also reduces secretion of human sex hormones and reduces sperm count in men, effects known to be caused by THC.

Results of the study are reported in the current (August 2) issue of Proceedings of the National Academy of Sciences.

The findings will help scientists understand the full biological role of this receptor, which has been preserved through millions of years of evolutionary history.

“Sea-urchin sperm are an ideal model system to determine how a cannabinoid receptor operates at the cellular level,” Schuel said. “We think these receptors play a general role in regulating how cells work. In this case, they inhibit secretion by the sperm. But we have reason to believe that anandamide and other cannabinoids regulate cellular functions in the human nervous system and in organs outside the nervous system.”

Scientists have long been aware that a cannabinoid receptor was present in human brain cells and that when THC binds to the these receptors, a variety of physical and neurological effects ensue, Schuel said. He was the first to report the existence of the cannabinoid receptor in sea-urchin sperm and to show that when THC linked to the receptor, the sperm were unable to fertilize an egg.

While scientists learned more about the receptor, they continued to question why the receptor existed at all, when THC does not exist naturally in the body. Part of the question was answered in 1992 when researchers at The Hebrew University of Jerusalem discovered the brain’s natural ligand for its cannabinoid receptor -- a chemical they named anandamide, from the Sanskrit word meaning “internal bliss.”

With the discovery of anandamide, Schuel repeated his THC-sea urchin sperm research using the naturally occurring brain chemical, producing his current findings.

He showed that anandamide, like THC, prevented sperm cells from undergoing an essential secretory process of fertilization called the acrosome reaction. During this process, sperm respond to a substance in the jelly-like layer surrounding the egg, causing the sperm acrosomal membrane to be exposed and allowing the sperm to attach to and penetrate the egg.

“These findings provide additional evidence that the cannabinoid receptor in sperm plays a role in blocking the acrosome reaction, indicate that anandamide or a related molecule may be the natural ligand for the cannabinoid receptor in sea-urchin sperm and suggest that binding of anandamide to the receptor modulates stimulus-secretion-coupling in sperm...,” Schuel stated.

Schuel noted that anandamide and THC may regulate sperm function prior to, as well as during, fertilization.

“If anandamide is present in seminal plasma, then it may help to keep the sperm quiet until they are diluted by sea water after spawning,” he said. “Anandamide also may be produced by the egg during fertilization...to prevent excess sperm in the vicinity from undergoing the acrosome reaction. Sperm that fail to undergo the acrosome reaction cannot fertilize eggs.

“If this hypothesis proves correct, anandamide may be one of several defense mechanisms that act together to ensure that only one sperm penetrates the egg during fertilization. Penetration of the egg by more than one sperm, called polyspermy, results in death of the embryo. ”

The gene for the cannabinoid receptor in the human brain also is expressed in the human testes, Schuel noted, which points to the possibility that mature human sperm also may contain a cannabinoid receptor.

“If this proves to be accurate,” Schuel said, “then our observations on the effects of anandamide and THC on the acrosome reaction and sperm-fertilizing capacity in sea urchins could be relevant to human reproduction.”

Schuel’s work is funded by the National Institute on Drug Abuse.

Researchers on this project, in addition to Schuel, were Elaine Goldstein of UB; Raphael Mechoulam, Ph.D., of The Hebrew University of Jerusalem; Arthur M. Zimmerman, Ph.D., of the University of Toronto, and Selma Zimmerman, Ph.D., of York University, Toronto.